Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive)

Review ArticleTraditional Uses Phytochemistry and Pharmacologyof Olea europaea (Olive)

Muhammad Ali Hashmi1 Afsar Khan1 Muhammad Hanif1

Umar Farooq1 and Shagufta Perveen2

1Department of Chemistry COMSATS Institute of Information Technology Abbottabad 22060 Pakistan2Department of Pharmacognosy College of Pharmacy King Saud University PO Box 2457 Riyadh 11451 Saudi Arabia

Correspondence should be addressed to Afsar Khan afsarhejgmailcom and Umar Farooq umarfciitnetpk

Received 26 November 2014 Revised 18 January 2015 Accepted 25 January 2015

Academic Editor Saeed Esmaeili-Mahani

Copyright copy 2015 Muhammad Ali Hashmi et alThis is an open access article distributed under the Creative CommonsAttributionLicense which permits unrestricted use distribution and reproduction in anymedium provided the originalwork is properly cited

Aim of the Review To grasp the fragmented information available on the botany traditional uses phytochemistry pharmacologyand toxicology of Olea europaea to explore its therapeutic potential and future research opportunities Material and MethodsAll the available information on O europaea was collected via electronic search (using Pubmed Scirus Google Scholar andWeb of Science) and a library search Results Ethnomedical uses of O europaea are recorded throughout the world where ithas been used to treat various ailments Phytochemical research had led to the isolation of flavonoids secoiridoids iridoidsflavanones biophenols triterpenes benzoic acid derivatives isochromans and other classes of secondary metabolites from Oeuropaea The plant materials and isolated components have shown a wide spectrum of in vitro and in vivo pharmacologicalactivities like antidiabetic anticonvulsant antioxidant anti-inflammatory immunomodulatory analgesic antimicrobial antiviralantihypertensive anticancer antihyperglycemic antinociceptive gastroprotective and wound healing activities Conclusions Oeuropaea emerged as a good source of traditional medicine for the treatment of various ailments The outcomes of phytochemicaland pharmacological studies reported in this review will further expand its existing therapeutic potential and provide a convincingsupport to its future clinical use in modern medicine

1 Introduction

Oleaceae family or the family of dicotyledons includes 30genera [1 2] of deciduous trees and shrubs including olivetree and its relatives numbering about 600 species [3] Thefamily is divided into several tribes that is FontanesieaeForsythieae JasmineaeMyxopyreae andOleeae [4 5]Theseare mostly native of all continents except the Antarcticincluding tropical subtropical and temperate regions of theworld [1 6] Oleaceae is best grown in Asia and Malaysiaespecially tropical and temperate regions of Asia [7]

The genus Olea got its name from the Greek ldquoelaiardquo andthe Latin ldquooleumrdquo but it is knownby nearly 80 different names(Table 1) [8]ThegenusOlea comprises 30 species [9] butOleaeuropaea L is the most popular member of the genus Olea[10] It is the only species of this genus which is used as food[11] and is found in the Mediterranean region [12]

Olive trees are normally distributed in the coastal areas ofthe easternMediterranean basin the contiguous coastal areasof southeastern Europe northern Iran at the south end of theCaspian Sea western Asia and northern Africa [13] Olivetree and its fruit are also important in context of religionOlives are narrated several times in the Bible both in theNew and Old Testaments [13] Olive has also been praised asa blessed tree and fruit in the Holy Quran (Quran Chapter24 Al-Noor Verse 35)

Olives are not used as a natural fruit because of theirextremely bitter taste but are rather consumed either as oliveoil or table olives [14] Olive oil market is very significant inthe olive industry as approximately 90of annually producedolives go for oil processing [15] Table olives and olive oilare very much important in industrial sectors of PalestineIsrael Spain and other Mediterranean areas Spain is thelargest producer of olives followed by Italy and GreeceThese

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 541591 29 pageshttpdxdoiorg1011552015541591

2 Evidence-Based Complementary and Alternative Medicine

Table 1 Common names of Olea europaea

S no Region Name

1 Spain Aceituna Olivera Olivo Oliondo OastreOliba

2 Lithuania Alyvos3 Portugal Azeitona Oliveira4 Romania Culoare masline Maslin Masliniu Oliva5 Albania Dege e ullirit Ngjyre ulliri Ulli6 Greece Elia7 Estonia Euroopa olipuu Olipuus8 Sweden Oliv Olivgront9 Slovakia Oliva europska10 Czech Republic Oliva Olivove drevo11 Latvia Olivas12 Denmark Oliven13 Germany Olivenbaum Olbaum14 Netherlands Olijf15 Israel Eylbert Masline Zayit16 India Jaitun Julipe Saidun17 Armenia Jitabdoogh Jiteni18 Bulgaria Maslina19 Croatia Maslinov20 South Africa Mohlware21 Hungary Olajbogyo Olajfa Oliva22 England Olewydden Olive23 Iceland Olifa24 Finland Oliivi Oljypuu25 Arab World Zaitoon26 France Oulivie Olive27 Switzerland Uliva28 Pakistan Zaitun29 Tanzania Zeituni30 Georgia Zetis

three countries are producing 60 of the worldrsquos total oliveproduction Outside these United States and Argentina arethe major producers of olive [16 17]

The therapeutic utilities of O europaea have been indi-cated in traditional medicine It has been known to reduceblood sugar cholesterol and uric acid It has also been usedto treat diabetes hypertension inflammation diarrhea res-piratory and urinary tract infections stomach and intestinaldiseases asthma hemorrhoids rheumatism laxative mouthcleanser and as a vasodilator Many phenolic compoundsespecially secoiridoids and iridoids [18] and their phar-macological activities have been the focus of attraction forscientists in the last decade [13 19] Oleuropein a majorconstituent of O europaea has got much attention and alot of work has been done on its pharmacological properties[20 21] Olive has widely been explored as a functional food[22 23] with various biophenols [24 25] and other bioactiveconstituents [26] Volatile constituents from olive oil and

their applications in flavor development have also been ahot area of the current research [27] A few reviews havebeen done on the phytochemistry of olive and olive oil inthe last decade [13 18 27 28] but the title plant is underimmense investigation by scientists all around the world[28 29] Continuous research is in progress to validate itstraditional medicinal uses which is described in detail in thepresent review

11 Botanical Description The olive tree (Figure 1(a)) is shortand thick generally from trees or shrubs to 10m in height Itstrunk possesses a large diameter typically bent and twisted Ithasmany reedy branches with opposite branchletsThe leavesare shortly stalked lanceolate sometimes ovate narrowoblong coriaceous leathery glabrous attenuate apex cute toacuminate margin entire pale green above with few scalesand silvery-whitish below in color petiole 5mm and 4ndash10 cmin length and 1ndash3 cm wide with 5ndash11 primary veins on eachside of the midrib and raised adaxially (Figure 1(b)) [30]The flowers are numerous bisexual or functionally unisexualsmall subsessile creamy white and feathery bulled mostlyon the wood of previous year (Figure 1(c)) Calyx is truncatewith four little teeth and corolla short with four lobes and is1-2mm long The olive fruit is small of which an outer fleshypart or skin surrounds a shell of hardened kernel The fruit isovoid blackish-violet when ripe normally 1ndash25 cm long andsmall in wild plants than in orchard cultivates (Figure 1(d))[31] The bark is pale grey in color (Figure 1(e)) [11]

O europaea is a monoecious plant [32] having bothperfect and imperfect flowers [15] so it depends on the windin which self- or cross-pollination occurs Cultivated plantsare normally pollinated by neighboring cultivars or even thewild form that is O sylvestris [33] Genetically O europaeais a diploid (2119899 = 46) species [34]

12 Cultivation The olive tree is one of the oldest cultivatedtrees on the planet earth [35] The cultivation of olive startedin ancient times and it dates back more than 7000 yearsAccording to archaeological reports olives were cultivated forcommercial purposes in Crete in 3000 BC by the Minoancivilization The use of olive oil for body health can be foundin ancient Greek literature [36] Earliest olive oil productiondates back to some 6500 years ago off the Carmel coast southof Haifa Israel [37] Olive trees spread to the West fromthe Mediterranean area into Italy Portugal Spain Greeceand France [38] Spanish Conquistadors in 1560 carried thecuttings and seeds of O europaea to Peru From there olivetrees spread to Mexico The Franciscan padres then carriedolives and other fruits from San Blas Mexico into CaliforniaOlive oil production began in San Diego in the next decade[39] It has been assumed that the cultivars around theMediterranean originated fromwildMediterranean olive andthen spread all around it [40]

Even though olive is now being cultivated in differentparts of the world the Mediterranean region is still servingas the major olive and its oil production area accounting forabout 98 of the worldrsquos olive cultivation [41] Nowadaysthere are more than 2000 cultivars in the Mediterranean

Evidence-Based Complementary and Alternative Medicine 3

(a)

(b)

(c)

(d)

(e)

Figure 1 Olea europaea (a) tree (b) leaves (c) inflorescence (d) ripe fruits (e) stem bark

basinwhich exhibit enormous diversity based onpit sizemor-phology and fruit morphology [42 43]

2 Phytochemistry

Phytochemical research carried out on O europaea had ledto the isolation of flavonoids flavone glycosides flavanonesiridoids iridane glycosides secoiridoids secoiridoid glyco-sides triterpenes biophenols [44] benzoic acid derivativesxylitol sterols isochromans sugars and a few other typesof secondary metabolites from its different parts (Figure 2)Phenolic compounds flavonoids secoiridoids and secoiri-doid glycosides [45] are present in almost all the parts ofO europaea

21 Constituents of the Bark Lignans like (minus)-olivil (54) (+)-cycloolivil (80) (+)-1-acetoxypinoresinol (45) (+)-1-hydrox-ypinoresinol (46) (+)-1-acetoxypinoresinol-410158401015840-O-methylether (47) and (+)-1-hydroxypinoresinol-410158401015840-O-methyl ether(48) have been isolated from the ether extract of the barkofO europaea [46 47]Three lignan glucosides that is (+)-l-acetoxypinoresinol-410158401015840-methyl ether-41015840-120573-D-glucopyrano-side (49) (+)-l-hydroxypinoresinol-41015840-120573-D-glucopyranoside(50) (+)-l-acetoxypinoresinol-41015840-120573-D-glucopyranoside (51)as well as esculin (76) and oleuropein (1) were isolatedfrom the bark of O europaea and O europaea ssp africana[48ndash50] The bark of O europaea contains (+)-fraxiresinol-1-120573-D-glucopyranoside (52) (+)-l-acetoxypinoresinol-41015840-120573-D-glucopyranoside (51) [51] the coumarins esculetin (77)scopoletin (78) and scopolin (79) [48 49]

22 Constituents of the Fruits and Seeds O europaea fruitscontain a considerable amount of flavonoids secoiridoidssecoiridoid glycosides [52] and phenolics such as tyrosol(83) hydroxytyrosol (84) and their derivatives [53ndash55]Some of hydroxytyrosol derivatives like hydroxytyrosol

rhamnoside (85) [56] hydroxytyrosol glucoside (86) [45 57]and methyl malate-120573-hydroxytyrosol ester (98) [58] wereisolated from olive fruit for the first time Isolation of newtyrosol derivatives tyrosol glucoside salidroside (89) and 1-oleyltyrosol (99) [59 60] along with cornoside (37) [20 52]2(34-dihydroxy-phenyl)ethanol (90) [61] halleridone (38)[52] and hydroxytyrosol-elenolate (14) [54 61ndash63] has alsobeen reported from the fruits of O europaea An importantand major phenolic compound present in natural tableolives is 34-dihydroxyphenylglycol (DHPG) (138) which isreported from natural as well as different cultivated olivesamples [64 65]

Galactolipids triacylglycerols and fatty acids were iso-lated from the fruits ofO europaea [66ndash68] Marra and Gior-dano reported the isolation of a diacylglycerol (30) from olivepulp showing an oleic as well as an elenoic acid residue [69]

Secoiridoids constitute a major portion of the leaves andfruits of O europaea Oleuropein (1) is the most abundantlyfound secoiridoid glycoside in the fruits of O europaea Alot of work has been done on isolation characterizationsynthesis and in silico studies of oleuropein [20 70ndash72]Oleuropein may also be used for chemical standardization ofthe plant and its extracts of medicinal interest [73] Aouidi etal developed a method for rapid quantitative determinationof oleuropein in O europaea leaves using mid-infrared spec-troscopy combined with chemometric analyses [74] A studyof the distribution of phenolic compounds in different partsof the olive fruit showed the presence of oleuropein (1)demethyloleuropein (3) [75] and verbascoside (100) [76] inall parts of the fruit whereas nuzhenide (25) [60 76] wasfound to be the most concentrated phenolic compound inthe seeds of olives [76 77] The seeds contain nuzhenide-oleoside (26) [60] Secoiridoids and their glycosides arefound in olive fruits and seeds 34-Dihydroxyphenylethyl-[(26-dimethoxy-3-ethylidene)tetrahydropyran-4-yl]acetate(31) has been reported from the olive fruit [78 79] Oleoside


OR

OO

H

HOHOOH

H

R

O

O

O

H

O

O

OO

O O

H

R

O

HO

O

O O

O

O

O

ORH

OO

Glucosyl

Rhamnosyl

Caffeoyl

p-Coumaroyl

H

H Hydroxytyrosol

H

H

O

O

OR1

OR1

R2

OR2

OR1

COOR3

COOR3

COCH3

COOR3

COOCH3

COOCH3

CH 3

COOCH3

COOCH3

O

OH

OH

R2

R1 R2 R3

R1 R2 R3

R1 R2 R3

Glucosyl

Glucosyl

Glucosyl

Glucosyl

OH

OHOH

OH

H

H

H

H

H

H H

H

OHOH

OH

OH

HO

HO

HO

HO

HOHO

HO

OHHOHO

H

HH H

H

H

HH

HH

H

H H

H H

H

H

H

CH3

CH3

CH3

CH3

OCH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3Oleuropein (1)

Ligstroside (2)

Demethyloleuropein (3)Oleuropein aglycone (4)

Ligstroside aglycone (5)Ligstroside aglycone

Methyl acetal (6)

Methyl ether (7)

3-O-120573-D-Gluco-pyranosyl-120573-D-glucopyranose



Oleuropein-3998400-O-120573-D-glucopyranoside (8)

Ligstroside-3998400-O-120573-D-glucopyranoside (9)

Oleuricine A (10)

Elenolic acid (11)Elenolic acid methyl ester (12)Elenolic acid glucoside (13)Hydroxytyrosil-elenolate (14)

HCH3

GlucosylHydroxytyrosol

Oleoside (15)Secologanoside (16)

6998400-120573-D-Glucopyranosyl

oleoside (17)

6998400-Rhamnopyranosyl

oleoside (18)

Caffeoyl-6998400-secologanoside (19)

Comselogoside (20)

Oleuricine B (21)

Oleuroside (22)

Secologanin (23)

Secologanoside (24)

6-O-120573-D-Gluco-pyranosyl-hydroxytyrosol

Nuzhenide (25) H

Nuzhenide oleoside (26) Oleoside

R2

R1

R1 R2

10-Hydroxy oleuropein aglycone (27)10-Hydroxy oleuropein aglyconedecarboxymethyl (28)

10-Hydroxy-10-methyl oleuropeinaglycone (29)

Oleuropein-3998400998400-

Figure 2 Continued


H H

O

O

O

OO

OHC

H

O

O

OH

OO

COOH

OO

O

O

H

H

H

O

O

O OO

R

O

O

O

OO

R O

O

O

O

H

O

H

O

O

OO

O

O

O

OO

O

O

H

O

O

OR

O

O

O

H

R

H

HO

O

O

O

O

O

O

OO

30

OHH

Ac

AcGlc

Glc

Glc

Glc

Ac

Ac

Hydroxytyrosol

H

H

H

HH

HH

CH3

OH

OH

OHOH

HO

HO

HOHO

HO

OHOH

OHOH OH

OH

OH

OHOH

OH

OHOH

OH

HO

HOHO

HOHO

HO

HOHO

HO

HOHO

HO

HO

HO

HO

HO

HOHOHO

HO

HO

HO

HO

R2R1

COOCH3

COOCH3 COOCH3

COOCH3

CH3

COOCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

CH3

H3C(H2C)7H3COOC

HOH2C

(H2 )7C

H3CO

OR2

OR1

Jaspolyoside (33)Jaspolyanoside (34)

Isojaspolyoside A (35)

Halleridone (38)

Cornoside (37)

R1 R2 R3

HHH

H

HH

H

OH

OH

OH

H

H

H

HHH

CH3

CH3

CH3

(+)-1-Acetoxypinoresinol (45)(+)-1-Hydroxypinoresinol (46)(+)-1-Acetoxypinoresinol-4998400998400-O-methyl ether (47)

(+)-1-Hydroxypinoresinol-

4998400998400-O-methyl ether (48)

(+)-1-acetoxypinoresinol-4998400-120573-D-glucopyranoside-4998400998400-O-methyl ether (49)(+)-1-Hydroxypinoresinol-4998400-120573-D-glucopyranoside (50)(+)-1-Acetoxypinoresinol-4998400-120573-D-glucopyranoside (51)(+)-Fraxiresinol-1-120573-D-glucopyranoside (52)(+)-Pinoresinol (53)

34-DHPEA-DETA (31)

6998400-O-[(2E)-26-Dimethyl-8-hydroxy-2-octenoyloxy]-secologanoside (32)

Oleacein (39)Dialdehydic elenolicacid decarboxymethyl (40)Dialdehydic elenolicester decarboxymethyl (41)

7998400998400-S-Hydroxyoleuropein (36)

R1 R2

R1 R2

OH

OHOH

OHCH3

7-Deoxyloganic acid (42)Loganic acid (43)Loganin (44)

COOCH3

(minus)-Olivil (54)Berchemol (55)3-Acetyloxy berchemol (56)

R3O

H3C

Figure 2 Continued


O

O

O

O

O

O O

H

O

O

O O O

O

H

HHHHHHHHHHHH

HHH

OO

O

HO

O

O

OH H OH H OHGlucosyl H OH H OH

H H Rutinosyl H OHH H Rutinosyl H H

Rutinosyl H OH H OHGlucosyl H H H OH

OH H Rhamnosyl H OHH H OH H HH H Glucosyl H OHH H OH H OH

Glucosyl H OH H OHH Glucosyl OH Glucosyl HH H OH H HH H Glucosyl H HH H Glucosyl H HH H H H H

HH H

H H

H

Glucosyl

Glucosyl

OH Rhamnosyl H H

HHH

H

HOH H Rhamnosyl HOH Glucosyl

Glucosyl

Glucosyl H HOH H H Rhamnosyl

Rhamnosyl

H Rhamnosyl H HOH Rhamnosyl- H H

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

HOHOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

OCH3

OCH3

COCH3

COCH3

OCH3

OCH3

OCH3

H3CO

H3CO

H3CO

H3C4998400-O-120573-D-Glucosyl-9-O-(6998400998400-deoxysaccharosyl)olivil (57)

Taxifolin (75)

OR6

OR1

OR2

Verucosin (58)

R1 R1

R1 R2

R1

R1 R2 R3 R4

R2

R1 R2

R1

R1

R1

R2

R7

R7R6

R5

R5

R4

R4

R3

R3

R2 R2

CH3

CH3

HHHHHHHHHHHHHHH

CH3

(+)-Cycloolivil (80)

OR4

OR2

OR3

Quercetin (59)Quercetin-7-O-glucoside (60)Luteolin-7-O-rutinoside (61)Apigenin-7-O-rutinoside (62)Rutin (63)Luteolin-7-O-glucoside (64)Quercetin-3-rhamnoside (65)Apigenin (66)Apigenin-7-O-glucoside (67)Luteolin (68)Quercitrin (69)Vicenin-2 (70)Chrysoeriol (71)Chrysoeriol-7-O-glucoside (72)Luteolin-74998400-O-diglucoside (73)Diosmetin (74)

CH3

CH3

Esculin (76)Esculetin (77)Scopoletin (78)Scopolin (79)

1-Phenyl-67-dihydroxy-isochroman (81)1-(3998400-Methoxy-4998400-hydroxy) phenyl-67-dihydroxy-isochroman (82)

apiofuranosyl

120573-Hydroxyacetoside (92)Suspensaside (93)Hellicoside (94)Orbanchoside (95)

Wedelosin (97)Acetoside (96)

Tyrosol (83)Hydroxytyrosol (84)

Hydroxytyrosolrhamnoside (85)Hydroxytyrosolglucoside (86)

Tyrosol acetate (87)Hydroxytyrosolacetate (88)Glucoside salidroside (89)2(34-Dihydroxy-phenyl) ethanol (90)Homovanillyl alcohol (91)

OR2

Figure 2 Continued


O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5

Methyl malate-120573-hydroxytyrosol ester (98)

1-oleyltyrosol (99)

Verbascoside (100)

120575-amyrin (109)Taraxerol (110)

Betulinic acid (111)Citrostadienol (112)

Obtusifoliol (115)

Gramisterol (116)

Cycloeucalenol (117)

120573-sitosterol (118)

OCH3

23-dihydrocaffeic acid (123)Phloretic acid (124)

4-O-methyl-D-glucuronic acid (125)

R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH

CH2OHErythrodiol (101)

Uvaol (102)

Ursolic acid (103)

Maslinic acid (104)Oleanolic acid (105)

Oleanolic aciddemethyl (106)120573-amyrin (107)

Urs-21205733120573-dihydroxy-12-en-28-oic acid (108)

Cycloartenol (113)

24-methylene cycloartenol (114)

OCH3

Caffeic acid (119)p-coumaric acid (120)Cinnamic acid (121)Ferulic acid (122)

Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3

Rosmarinic acid (126) Protocatechuic acid (127)Gallic acid (128)

Shikimic-acid (129)Vanillin (130)Vanillic acid (131)

3-[1-(hydroxymethyl)-(E)-1-propenyl]glutaric acid (132)3-[1-(formyl)-(E)-1-propenyl] glutaric acid (133)

15-anhydroxylitol (134)

Poly-unsaturated di-galactoside glycerol diester (135)

34-dihydroxyphenylglycol (138)

Hemiacetal of dialdehydicoleuropein aglycone decarboxymethyl (136)Hemiacetal of dialdehydicligstroside aglycone decarboxymethyl (137)

34-dihydroxyphenylethyl 4-formyl-3-formylmethyl-4-hexenoate (139)4-hydroxyphenylethyl 4-formyl-3-formylmethyl-4-hexenoate (140)

CH3

Figure 2 Chemical structures of the compounds isolated from O europaea

(15) was isolated from the seeds of olive fruit [60] Elenolicacid glucoside (13) was isolated from olive pulp andwas characterized on the basis of LC-MS [53 57] 61015840-120573-Glucopyranosyl oleoside (17) 61015840-rhamnopyranosyl oleo-side (18) and ligstroside (2) were identified in peel pulp andfruits of O europaea by electrospray ionization mass spec-trometry [57] Ligstroside aglycone methyl acetal (6) wasreported from the olives of Hojiblanca cultivar [58]

A large number of flavonoids such as quercetin (59) [80]quercetin-7-O-glucoside (60) luteolin-7-O-rutinoside (61)[56 80] apigenin-7-O-rutinoside (62) [80 81] rutin (63)[57 80 81] vicenin-2 (70) chrysoeriol (71) chrysoeriol-7-O-glucoside (72) [80] luteolin-7-O-glucoside (64) [57 80]quercetin-3-rhamnoside (65) apigenin (66) [57] and quer-citrin (69) [45] have been reported from the fruits and pulpof the olives

Triterpene alcohols 120575-amyrin (109) taraxerol (110)cycloartenol (113) and 24-methylene cycloartenol (114) alongwith 4-monomethylsterols obtusifoliol (115) gramisterol

(116) cycloeucalenol (117) and citrostadienol (112) wereidentified in ripening olive fruits [82] Two secoiridoids withcaffeoyl moieties that is caffeoyl-61015840-secologanoside (19) andcomselogoside (20) were isolated by ultrasound-assistedsolid liquid extraction (USLE) of the olive fruits [45] Dif-ferent acids include caffeic acid (119) [56 57] 23-dihy-drocaffeic acid (123) phloretic acid (124) [55] 4-O-methyl-D-glucuronic acid (125) and betulinic acid (111) [83] 3-[1-(Hydroxymethyl)-(E)-1-propenyl]glutaric acid (132) and 3-[1-(formyl)-(E)-1-propenyl]glutaric acid (133) were isolatedfrom the ethyl acetate extract of olives [84] Pentacyclic trit-erpenoids including erythrodiol (101) uvaol (102) [85] urso-lic acid (103) [83] and maslinic acid (104) [83 86 87] wereisolated from the fruits of different varieties of O europaea

Golubev et al analyzed the tocopherols profile of olivefruits and found that 120572- 120573- and 120574-tocopherols were presentas 393mg 122mg and 240mg per kilogram of the samplerespectively [88] Qualitative and quantitative profiling ofsugars in vegetal tissues from olive fruits leaves and stems


resulted in monosaccharides disaccharides trisaccharidessugar carboxylic acids and alcohols cyclic polyols andderived compounds [89] Olive pomace extracts were ana-lyzed by tandem LC-MS and a number of phenolic com-pounds including 7-deoxyloganic acid (42) loganic acid (43)loganin (44) secologanin (23) secologanoside (24) taxifolin(75) rosmarinic acid (126) ferulic acid (122) cinnamic acid(121) shikimic acid (129) protocatechuic acid (127) andgallic acid (128) were identified [56]

23 Constituents of the Leaves Oleuropein has been reportedfrom the methanolic extract of boron deficient leaves peelpulp seeds and wood of O europaea [20 47 75 90ndash93]Oleuropein and other secoiridoids such as secologanoside(16) oleoside (15) 61015840-E-p-coumaroyl-secologanoside (com-selogoside) (20) and 61015840-O-[(2E)-26-dimethyl-8-hydroxy-2-octenoyloxy]-secologanoside (32) have been isolated fromthe methanolic extract of boron deficient leaves [94] Oleo-side (15) has also been isolated from water extract of Oeuropaea leaves [56 94] Oleoside (15) reported from fruitsis also present in leaves [60] hydroxytyrosol-elenolate (14)elenolic acid methyl ester (12) and ligstroside (2) wereisolated from the chloroform soluble fraction of O europaealeaves [95] The ethyl acetate extract of olive leaves yieldedtwo new secoiridoid glycosides oleuricine A (10) and oleu-ricine B (21) [87] Oleuroside (22) and 34-DHPEA-EDA(oleacein) (39) were isolated from the aqueous extract of theleaves of O europaea [57 91 96]

Isolation from ethyl acetate soluble fraction of O euro-paea leaves yielded different triterpenoids like120573-amyrin (107)[87 97] 120573-sitosterol (118) [97] oleanolic acid (105) [98ndash103]erythrodiol (101) [97 101 104] and urs-21205733120573-dihydroxy-12-en-28-oic acid (108) Other triterpene acids isolated fromO europaea leaves include betulinic acid (111) uvaol (102)ursolic acid (103) and maslinic acid (104) [85]

Flavonoids also constitute some portion of O europaealeaves Apigenin-7-O-rutinoside (62) rutin (63) and lute-olin-7-O-glucoside (64) were isolated from the leaves of Oeuropaea [80 81] Analysis and quantification of leaves of Oeuropaea from different cultivators showed the presence offlavone glycosides that is luteolin-741015840-O-diglucoside (73)diosmetin (74) and apigenin-7-O-glucoside (67) [81 91]

A lignan 41015840-O-120573-D-glucosyl-9-O-(610158401015840-deoxysaccharo-syl)olivil (57) was reported from the leaves of O europaea[105] A compound never found previously in the vegetalkingdom that is 15-anhydroxylitol (134) was isolated fromO europaea leaves [106] Two new compounds 34-dihy-droxyphenylethanol-elenolic acid dialdehyde (34-DHPEA-EDA) (39) and hydroxytyrosol-elenolate (14) which are thehydrolysis products of oleuropein (1) were isolated from theleaves of O europaea [107] Besides hydrocarbons esterswaxes triglycerides tocopherols esterols lineal terpenicalcohols and terpenic dialcohols have also been reportedfrom the hexane extract of O europaea leaves [108]

24 Constituents of Olive Oil and EVOO Olive oil is a veryrich source of biophenolic compounds and possesses manyinteresting biological properties [92 109] Presence of

hydroxytyrosol (84) hydroxytyrosol acetate (88) [110 111]and 34-dihydroxyphenylethyl-[(26-dimethoxy-3-ethylide-ne)tetrahydropyran-4-yl]acetate (31) has been reported inEVOO (extra virgin olive oil) and olive oil [56 111] LC-NMRanalysis of alperujo fresh solidwaste of two-phase oliveoil extraction system showed the presence of 120573-hydrox-yacetamide (92) suspensaside (93) hellicoside (94) orban-choside (95) acetoside (96) and wedelosin (97) [112] Hy-droxytyrosol-elenolate (14) oleuropein aglycone (4) ligstro-side aglycone (5) 10-hydroxy oleuropein aglycone (27) 10-hydroxy oleuropein aglycone decarboxymethyl (28) 10-hy-droxy-10-methyl oleuropein aglycone (29) elenolic acid (11)dialdehydic elenolic acid decarboxymethyl (40) dialdehydicelenolic ester decarboxymethyl (41) vanillic acid (131) p-coumaric acid (120) and (+)-pinoresinol (53) have beenreported from olive oil and EVOO obtained from variouscultivators [56 57 95 111 113 114] Christophoridou et alidentified various phenolic compounds in olive oil by coup-ling HPLC with post column solid-phase extraction tonuclear magnetic resonance spectroscopy (LC-SPE-NMR)These include tyrosol acetate (87) vanillin (130) homovanil-lyl alcohol (91) (+)-1-acetoxypinoresinol (45) berchemol(55) 3-acetyloxy berchemol (56) hemiacetal of dialdehydicoleuropein aglycone decarboxymethyl (136) hemiacetal ofdialdehydic ligstroside aglycone decarboxymethyl (137) andverucosin (58) [110] Flavonoids such as apigenin (66) andluteolin (68) [80 81] other phenolics including 34-dihy-droxyphenylethyl-4-formyl-3-formylmethyl-4-hexenoate(139) and 4-hydroxyphenylethyl-4-formyl-3-formylmethyl-4-hexenoate (140) [75 111] and isochromans that is 1-phe-nyl-67-dihydroxy-isochroman (81) and 1-(31015840-methoxy-41015840-hydroxy)phenyl-67-dihydroxy-isochroman (82) [115] havealso been reported from olive leaves oil and EVOO Adi-galactoside of a poly-unsaturated diester of the glycerol(135) was also isolated from olive oil [67]

25 Constituents of the Wood Many important secondarymetabolites have been reported from the wood of O euro-paea Ligstroside (2) a major component of olive fruitand seeds is also present in the wood [76] Perez-Bo-nilla et al isolated oleuropein-310158401015840-methyl ether (7) 710158401015840-S-hy-droxyoleuropein (36) oleuropein-31015840-O-120573-D-glucopyrano-side (8) ligstroside-31015840-O-120573-D-glucopyranoside (9) jaspol-yoside (33) jaspolyanoside (34) and isojaspolyoside A (35)from the ethyl acetate fraction of olive wood [116] An iridoidglycoside 7-deoxyloganic acid (42) was isolated from ethylacetate extract of olive wood [47] A new compound knownas oleanolic acid demethyl (106) has been reported from thestem of O europaea [117]

3 Traditional and Contemporary Uses

O europaea has a number of traditional and contemporaryuses in medicine Some of its exemplary uses are given belowwhile the others are summarized in Table 2 O europaea isextensively used in traditional medicine for a wide rangeof ailments in various countries Its bark fruits leaveswood seeds and oil are used in different forms alone orsometimes in combination with other herbs Oil of seeds


Table 2 Traditional and contemporary uses of Olea europaea

S no Partpreparation used Ailmentuse Reference1 Leaves and fruitsinfusions and macerations Hypoglycemic hypotensive [142]2 Decoction or infusion of fruits and leaves Antidiabetic [140]3 Olive oil + lemon juice To treat gallstones [139]4 Oil of seedstaken orally Laxative [118]5 Decoctions of dried leaves and fruitoral use Diarrhea respiratory and urinary tract infections [119]6 Olive oilapplied on scalp To prevent hair loss [120]7 Boiled extract of fresh leavestaken orally To treat asthma [124]8 Boiled extract of dried leavestaken orally To treat hypertension [131 258]9 Leaves extract in hot water Diuretic [130]10 Olive oil Applied over fractured limbs [132]11 Infusion of leavesoral use Antipyretic [127]12 Olive fruit Skin cleanser [133]13 Infusion of leavesoral use Anti-inflammatory tonic [258]14 Leaf preparations To treat gout [134]15 Leaves of O europaea Antibacterial [135]16 Decoction of leaves Antidiabetic antihypertensive [138]17 Fruits and leaves Hemorrhoids rheumatism and vasodilator [136]18 Infusions of leaves Eye infections treatment [137]

is taken orally as a laxative and also applied externally asa balm for inflammation [118] Decoctions of dried leavesand fruit are used orally to treat diarrhea respiratory andurinary tract infections stomach and intestinal diseases andas mouth cleanser [119] Continuous application of olive oilis also useful to prevent hair loss [120] In Canary Islandsthe infusion prepared from olive leaves is taken orally asa hypotensive while it is administered through rectum forhemorrhoids [121 122] In East-Africa the infusion of the barkof olive tree is taken for tapeworm infestation after soakingfor whole night [123] In Greece hot water extract of oliveleaves is taken orally to treat high blood pressure [124] InItaly the extract of the essential oil of fruit is taken orally totreat renal lithiasis It is applied externally to treat burns oresand rheumatism and to promote circulation [125] Infusion offresh leaves is also taken as anti-inflammatory [126] Tinctureof olive leaves is taken in Italy as a febrifuge [127] and appliedexternally as an emolument for ingrown nails and a restorerof epithelium [128] In Japan olive leaves are taken orally forstomach and intestinal diseases and their essential oil is usedorally for constipation and liver pain [119]

Olive oil has been taken orally to treat hypertension andagitation as a laxative and vermicide in the United States[129] Boiled extract of fresh or dried leaves is taken orallyto treat asthma [124] and hypertension and to induce diuresis[130 131] The oil is applied externally over fractured limbs[132] and fruit is also known to be a skin cleanser [133]Infusion of leaves is taken orally to reduce fever [127] and asanti-inflammatory tonic [126] O europaea leaf preparationsare used as a common remedy for gout inMediterranean folkmedicine [134] Leaves of O europaea are used in Tunisianfolk medicine as a remedy for many inflammation typesand bacterial infections such as gingivitis otitis icterus andcough [135] Fruits and leaves ofO europaea are used to treat

hemorrhoids and rheumatism and as vasodilator in vasculardisorders [136] Infusions of leaves are used as ointment totreat eye infections or as mouthwash to relieve sore throat[137] Hot water extract of the fresh leaves of O europaeais taken orally to treat hypertension and to induce diuresisin Brazil [131] Decoction of leaves is used in Morocco totreat hypertension and diabetes [138] Olive oil is mixed withlemon juice and is used to treat gallstones [139] Decoctionor infusion of the fruits and leaves is used in Palestine totreat diabetes [140 141] In Algeria the fruits and leaves of Oeuropaea are used to cure diabetes and hypertension [142]

4 Pharmacology

41 Antidiabetic Activities The ethnomedical use of Oeuropaea in treatment of diabetes has been validated inseveral experimental studies (summarized in Table 3) Theplant has been used by the folk medical practitioners totreat diabetes Al-Azzawie and Alhamdani proposed thatantidiabetic patientsmay be treatedwith good antioxidants asthe relief in oxidative stress reduces the blood glucose levelsSo they treated hypoglycemic alloxan-diabetic rabbits witholeuropein a powerful antioxidant agent present abundantlyin olive leaves and fruit to reduce their oxidative stressThe diabetic rabbits were treated with oleuropein (20mgKgbody weight) for up to 16 weeks After treatment it wasobserved that the blood glucose levels along with most of theantioxidants were restored to the values near to the normalcontrol rabbits The study proved the effects of oleuropein asantihyperglycemic and antioxidative agent [143]

It was believed that the antidiabetic effects ofO europaeaare solely due to the major secoiridoid glycoside oleuropein(1) present in its different parts Sato et al isolated thenamed oleanolic acid (105) and showed that it was an agonist


Table 3 Antidiabetic activities of Olea europaea

S no Parttype ofextractcompound Diseaseassay Animal model Effective dose Reference drug Reference

1 Olive leaf biophenols(oleuropein + hydroxytyrosol)

Insulin sensitivityimprovement

Middle aged overweightmen 588mg mdash [151]

2 Aqueous extract of leaves Antidiabetic assay Streptozotocin induceddiabetic rats 200mgKg Metformin [259]

3 Oleanolic acid Diabetic neuropathyprevention Sprague Dawley rats 60mgKg Streptozotocin [149]

4 Ethanolic extract of leaves Antidiabetic activity Male adult Wistar rats 05 gKg Glibenclamide [146]

5 Oleuropein andhydroxytyrosol

Antidiabetic and antioxidantactivities Adult male Wistar rats 16mgKg Trolox [145]

6 Oleuropein Hypoglycemic andantioxidant effect

Male New Zealandrabbits 20mgKg Alloxan [143]

7 Oleanolic acid Antihyperglycemic activity In vitro mdash Oleuropein [144]

8 Oleanolic acid demethyl 120572-Amylase and lipaseinhibition In vitro mdash Oleuropein [117]

for TGR5 (the first cell surface receptor activated by bileacids) a member of G-protein coupled receptor and it sig-nificantly lowered serum glucose and insulin levels in micefed with a high fat diet and also enhanced glucose toleranceThey suggested on the basis of their findings that botholeuropein (1) and oleanolic acid (105) were responsible forthe antidiabetic effects of olive leaves [144] Later on thefindings of Al-Azzawie and Alhamdani were supported bythe studies of antidiabetic and antioxidant effects of oleu-ropein (1) and hydroxytyrosol (84) isolated from theleaves of O europaea in alloxan-induced diabetic rats Therats suffered from hyperglycemia increased lipid peroxi-dation hypercholesterolemia and depletion in the antioxi-dant enzymes activities After administration of oleuropeinand hydroxytyrosol rich extracts having approximately 8ndash16mgKg body weight of each compound for four weeks theserum cholesterol and glucose levels of the diabetic rats weresignificantly lowered and antioxidant enzymatic activitieswere restored It was suggested that the antidiabetic effect ofoleuropein and hydroxytyrosol might be due to their abilityto restrain the oxidative stress which is widely associated withpathological complications of diabetes [145]

A comparative study was conducted to check the effect ofolive leaves extract in normal and diabetic rats The diabeteswas induced in rats by injecting streptozotocin The ratswere orally administered with olive leaves extracts at differentdoses of 100 250 and 500mgKg of body weight whilethe reference drug Glibenclamide was given at a dose of600120583gKg for 14 days The antidiabetic effect of the extractwas more potent than the reference drug GlibenclamideMore interestingly the extracts besides lowering the serumglucose total cholesterol urea uric acid triglycerides andcreatinine also increased the serum insulin levels in diabeticand not in normal rats The study proposed that olive leafextract may be used as an antidiabetic agent [146] Thesestudies demonstrated the effect of olive leaves extract andoleuropein on diabetes but did not explain the cellular mech-anisms of these effects which are responsible for controllingblood glucose levels including the effects on insulin secretion

and any relation with cellular redox state Cumaoglu et alinvestigated the effects of biophenolic olive leaf extract (OLE)and oleuropein (1) on intracellular oxidative stress apoptosisnecrosis and insulin secreting function in the INS-1 cell lineThe cells were exposed toH

2O2for 45minutes which resulted

in a depressed glucose-stimulated insulin secretion increasedapoptotic and necrotic cell death inhibited glutathione per-oxidase activity (GPx) and stimulated the catalase activitythatwere associatedwith increased intracellular generation ofreactive oxygen species (ROS) These cells were then treatedwith OLE and the reference oleuropein Both improvedpartly necrotic and apoptotic cell death and inhibited theROSgeneration and improved the secretion of insulin in H

2O2-

exposed cells The results showed that oleuropein had morepronounced effect on insulin secretion thanOLE [147] It wasprobably due to the presence of other biophenols in OLEwhich suppressed the properties of oleuropein which it mightexpress alone [148]

A new compound has been reported from the stem ofO europaea which is an isomer of oleanolic acid (105) andwas known as oleanolic acid demethyl (106)This compoundexhibited excellent inhibitory activities in vitro against 120572-amylase and lipase enzymes [117] Recently the effect ofoleanolic acid on streptozotocin-induced diabetic neuropa-thy in Sprague Dawley rats has been studied [149] The ratswere divided into control group and diabetic group and weredaily treated with 20 40 and 60mgKg doses of oleanolicacid up to four weeks The results indicated that 60mgKgdose of oleanolic acid was more active which reduced theoxidative stress in the kidneys and inhibited the neuropathyinduced alterations Oleanolic acid proved to act viamultiplemechanisms that is antioxidant mechanism via inhibitionof generation of advanced glycation end products improvingthe insulin secretion Al-Qarawi et al studied the effect offreeze-dried extract of olive leaves on the pituitary-thyroidaxis in rats and showed that the thyroid hormones in turndecrease the levels of cholesterol and sugar [150]

A placebo-controlled crossover trial was conducted inNew Zealand to evaluate the effect of supplementation with


Table 4 Anticancer activities of Olea europaea

S no Parttype ofextractcompound Cell line used Activity Reference drug Reference

1 Maslinic acid HT29 human colon cancer cell line Dose dependent activity Hydroxytyrosol [161]

2 Hydroxytyrosol andhydroxytyrosyl laurate Human monocytoid cell line The best H2O2 [158]

3 Oleanolic acid Human hepatoma cell line HepG2 Good mdash [157]4 Methanolic extract of leaves Human leukemic cell line High activity 5-Bromodeoxyuridine [156]

5Erythrodiol uvaol

oleanolic acid and maslinicacid

MCF-7 human breast cancer cell lines High activity Trolox [155]

6 Water and methanolicextracts of olive leaves

Human breast adenocarcinoma (MCF-7)human urinary bladder carcinoma (T-24)and bovine brain capillary endothelial

(BBCE)

Good FGF-2 [154]

7 Aqueous extract of leavesMKN45 (stomach cancer) MFC7 (breastcancer) NCI-H460 (lung cancer) HCT116

(colon cancer)Good MTT [171]

8 Olive leaf extract MKN45 HCT116 NCI-H460 and MCF7 Good mdash [171]9 Erythrodiol HT-29 human adenocarcinoma cells Dose dependent activity Caspase-3 [153]10 Maslinic acid HT29 human colon cancer cell line Dose dependent activity Hydroxytyrosol [160]

11 Virgin olive oil phenolicsextract HT115 human colon cancer cells Dose dependent activity mdash [260]

12 Oleuropein HeLa human cervical carcinoma cells Good mdash [261]

olive leaf biophenols on insulin action and cardiovascular riskfactors in middle-aged overweight men 46 participants wereselected to receive capsules of olive leaves extract or placebofor 12 weeks The results concluded that OLE (olive leafextract) supplementation resulted in a 15 improvement ininsulin sensitivity compared to placeboThere were howeverno effects on lipid profile ambulatory blood pressure bodycomposition or liver function [151]

42 Anticancer Activities Constituents of O europaea haveshown very good anticancer activities on various types ofcancers [152] The anticancer activities of O europaea aresummarized in Table 4 Juan et al investigated the antiprolif-erative and apoptotic activities of erythrodiol (101) in humancolorectal carcinoma HT-29 cells [153] It inhibited the cellgrowth without any toxicity in a concentration range of100 120583M in colon adenocarcinoma cells Similarly studieshave been conducted on water and methanolic extracts ofolive leaves against cancer and endothelial cells These crudeextracts were found to inhibit cell proliferation of humanbreast adenocarcinoma (MCF-7) human urinary bladdercarcinoma (T-24) and bovine brain capillary endothelial(BBCE) Upon phytochemical analysis of these extractsoleuropein was found to be the most abundant compoundalong with other phenolics and flavonoids Then the isolatedpure compounds luteolin 7-O-glucoside (64) oleuropein (1)hydroxytyrosol (84) and hydroxytyrosol acetate (88) werealso subjected to cell proliferation assays It was concludedthat in pure form these compounds were active in low con-centrations [154]

Allouche et al investigated effects of erythrodiol (101)uvaol (102) oleanolic acid (105) and maslinic acid (104) on

cytotoxicity apoptosis cell proliferation cell cycle reactiveoxygen species (ROS) and oxidative DNAdamage on humanMCF-7 breast cancer cell line The results showed that ery-throdiol uvaol and oleanolic acid have a significant cytotoxiceffect and inhibit proliferation in a dose- and time-dependentmanner All these compounds protected against oxidativeDNA damage at the concentration 10 120583M Overall resultsshowed that the stated triterpenes have significant naturaldefense against human breast cancer [155] The ethanolicextract of the leaves of a Lebanese olive plant were testedon human leukemic cell line Cytotoxicity of the variousconcentrations of this extract was also determined WST-1proliferation kit and [3H]-thymidine incorporation methodwas used for antiproliferation assay The extract showeda concentration-dependent activity by inducing apoptosisAntioxidant activity of the extract was also determinedby DPPH scavenging method [156] Antitumor effects ofoleanolic acid (105) have been investigated recently bothin vitro and in vivo HepG2 cells were injected subcuta-neously to mice to establish transplanted tumors Oleanolicacid exhibited inhibitory effect on hepatocellular carcinomathrough induction of apoptosis and cell cycle arrest bothin transplanted tumors and in HepG2 cells The resultsdemonstrated that oleanolic acid has significant antitumoractivities in hepatocellular carcinoma both in vitro and invivo models [157] Recently Burattini et al investigated theeffects of hydroxytyrosol and its ester hydroxytyrosol lauratein U937 cells a human monocytoid cell line and in C2C12myoblasts (a murine proliferating muscle cell model) afterapoptotic death induction H

2O2at known concentrations

was used to induce apoptosis The results revealed thathydroxytyrosol laurate has a greater protective antioxidant


effect against H2O2treatment than hydroxytyrosol [158]The

effect of olive leaf biophenols like oleuropein (OLP) andhydroxytyrosol (HT) was studied on tumor growth in breastcancer It was observed that the treatment with 150 and225mgKgday of OLE significantly reduced the tumor vol-ume and weight [159]

Maslinic acid (104) a triterpenoid reported from oliveleaves and fruit is an antitumor agent which showed potentantiproliferative properties against the HT29 colon cancercells [160] It affects the levels of structural proteins necessaryto themaintenance of cell structure and function and inhibitsthe cell growth by G1 cell cycle arrest indicating its therapeu-tic potential in colon cancer therapy [161 162]

Oleuropein (1) the most prominent phenolic compoundpresent in the olive tree has been evaluated for its activity onhuman colon adenocarcinoma (HT-29) cells in comparisonwith its hydrolysis product hydroxytyrosol (84) to elucidatethe underlying mechanisms of action The sulforhodamineB (SRB) assay was used to detect cell proliferation whileflow cytometry and Western blot procedures were used inorder to assess apoptosis and changes in regulation of HIF-1120572and p53 respectively Cell growth inhibition results showedhydroxytyrosol more active than oleuropein but in case ofapoptotic population and oleuropein showed a significantincrease The results demonstrated that oleuropein limits thegrowth and induces apoptosis in HT-29 cells via p53 pathwayactivation adapting the HIF-1120572 response to hypoxia [163]Oleuropein (1) and OLE were studied for their effects onunstimulated lymphocytes It was noticed that it did notproduce any cytotoxic effects but had a stimulatory effect andinduced high proliferation in lymphocytes in a concentrationdependent manner [164]

43 Antimicrobial Activities O europaea has been used as afolk remedy for the cure of numerous infectious disordersof bacterial fungal and viral origin Several studies havebeen carried out in the past validating the antimicrobial andantiviral potential of O europaea (summarized in Table 5)[165] Kubo et al characterized a series of long-chain 120572120573-unsaturated aldehydes from O europaea fruit and its oilflavor for their antimicrobial activities and found them activeagainst a broad spectrum of microbes [166] Pereira et altested the extracts of various table olives from differentcultivators of Portugal for their antimicrobial potential andfound that besides having good antioxidant potential olivephenolics possess good antimicrobial activity suggesting thatthese table olives may be good candidates against bacteriaresponsible for human gastrointestinal and respiratory tractinfections [167]

It was observed that olive brines have antimicrobialactivity against lactic acid fermentationA studywas designedto investigate their antimicrobial activity The samples ofthese olive brines were analyzed by HPLC electrospray ion-ization mass spectrometry and NMR spectroscopic studiesAmong the identified compounds the dialdehydic form ofdecarboxymethyl elenolic acid linked to hydroxytyrosol (39)showed the strongest antilactic acid bacteria activity and itspresence in olive brines also explained the growth inhibi-tion of these bacteria during fermentation of olives [168]

Ethanolic extract of the fresh leaves ofO europaeawas testedagainst Artemia salina and was found to be active Its lethaldose was 164 pgmL [169] Sudjana et al investigated thecommercial olive leaf extract against awide range ofmicrobes(119899 = 122) using agar dilution and broth microdilutiontechniquesThe results showed that olive leaf extract was onlyactive against Campylobacter jejuni Helicobacter pylori andStaphylococcus aureus showing that it is not a broad spectrumantimicrobial agent [170] Olive leavesrsquo phenolic compoundswere also evaluated against several microorganisms that arecausative agents of human intestinal and respiratory tractinfections including Gram positive bacteria (Bacillus cereusB subtilis and Staphylococcus aureus) Gram negative bacte-ria (Pseudomonas aeruginosa Escherichia coli and Klebsiellapneumoniae) and fungi including Candida albicans andCryptococcus neoformans The extracts showed an unusualcombined antibacterial and antifungal activity at low con-centrations against the stated species which suggest theirpotential as nutraceuticals [167]The olive leaf extracts exhib-ited relatively high antimicrobial activity against Salmonellatyphimurium Escherichia coli Staphylococcus aureus Bacilluscereus Listeria monocytogenes and Pseudomonas aeruginosausing disc diffusion method [171] The in vitro antimicrobialactivity of aqueous acetone diethyl ether and ethyl alcoholextracts of olive leaves was investigated against a numberof microorganisms The aqueous extract of olive leaves hadno antibacterial effect against the test microorganisms whileacetone extract inhibited several microorganisms includingSalmonella enteritidis Klebsiella pneumoniae Bacillus cereusEscherichia coli Streptococcus thermophiles Enterococcus fae-calis and Lactobacillus bulgaricus [172] O-H Lee and B-YLee studied the combined effect of olive leaf phenolics andthe isolated compounds against several microbial strainsTheresults indicated the active components as oleuropein (1) andcaffeic acid (119) and it was concluded that the combined olivephenolics have a significantly higher antimicrobial effect thanthe isolated phenolics [173] Other studies have been con-ducted to observe the antimicrobial activities of olive leavesrsquoextracts Oleuropein was found the most effective compoundwhile syringic acid was found inactive Aqueous extract wasinactive against Bacillus cereus while acetone extract wasfound active [172 174] Volatile fractions from fresh anddried leaves of three Tunisian olive cultivators were subjectedto GC-MS analysis and their antibacterial and antifungalactivities were evaluated All the fractions showed significantantibacterial and antifungal activities although there weredifferences in the responses of different cultivators to themicroorganisms because of variability of the composition[175] Another study was designed to investigate the effectsof alcoholic extract of olives on the bacterial communicationsystem expressed as quorum sensing activityThe extract wastested for the stated activity by Chromobacterium violaceumassay using the agar cup diffusion method The extract ofolives was not found active for antiquorum sensing activity[176]

The bactericidal and fungicidal activities of salt-freetable olive solutions were evaluated against several phy-topathogenic microorganisms [177] The results demon-strated that the storage solutions of black ripe olives showed


Table 5 Antioxidant and antimicrobial activities of Olea europaea

S no Parttype ofextractcompound Assay Activity Methodreference drug Reference

1 Leaves extract Antioxidant High Oxidation of soybeanunder microwaves [213]

2 Olive leaves infusion Antioxidant GoodHydroxyl and 22-diphenyl-1-picrylhydrazyl (DPPH)

radicals[196]

3 Ethanolic extract of leaves Antioxidant High DPPH radicals [197]4 Olive fruit Antioxidant Good DPPH radicals [199]

5 Volatile fractions of leaves Antibacterial andantifungal Moderate to high Microwell dilution

assayDMSO [175]

6 Aqueous extract of leaves Antimicrobial Remarkable Paper disc diffusionmethoderythromycin [174]

7 Acetone extract of leaves Antibacterial Good Paper disc diffusionmethodoleuropein [172]

8 Fruit and leaves Antioxidant Good DPPH radicals [136]9 Olive pulp Antioxidant Excellent Vitamin C [211]10 Alperujo (olive waste) Antimicrobial Good Syringic acid [177]

11 Volatiles of olive fruits Antibacterial andantifungal Moderate Amphotericin levofloxacin [181]

12 Aqueous extract of leaves Antioxidant Good Trolox [208]13 Leaf extract Antioxidant Good DPPH radicals [200]

14 Aqueous solutions from tableolives

Antibacterial andantifungal Good Streptomycin

oxytetracycline [178]

15 Leaves extract Antioxidative stress Moderate MTT assayoleuropein [147]

16 Maslinic acid Antiparasitic Dose dependent Phenylmethanesulfonylfluoride [182]

17 Dry extract of table olives Antioxidant Very good Trolox [204]

18 Acetone extract of olive leaves+ oleuropein Antibacterial Very good Oleuropein [172]

19 Leaf extract Antioxidant andantimicrobial Excellent Oleuropein [173]

20Oleuropein aglycones34-DHPEA-EA and34-DHPEA-EDA

Anti-oxidative damage toerythrocytes Good Hydroxytyrosol [207]

21 High strength leaf extract Antimicrobial Excellent mdash [170]22 Dhokar cultivar olives Antioxidant Good DPPH radicals [201]

23 Aqueous leaf extract Antioxidant andantimicrobial Good DPPH

radicalsstreptomycin [171]

24 Leaf extract Antioxidant andantimicrobial Dose dependent Ascorbic acid [171]

25Phenolics released by

hydrothermal treatment ofolive tree pruning

Antioxidant Good Trolox [205]

26 Leaf extract Antioxidant Good Trolox [262]27 Aqueous extract of leaves Antifungal The best Oleuropein [179]28 Aqueous extract of leaves Antimicrobial Good mdash [167]

29 Dialdehydic form ofdecarboxymethyl elenolic acid Antimicrobial More potent than

oleuropein Hydroxytyrosol [168]

30 Leaves sprayed with copperformulations Antioxidant

Low activity due todecrease in

phenolic content

120572-Tocopherol and gallicacid [206]

31 Aqueous ethanolic extract Antioxidant activity Good 120572-Tocopherol and gallicacid [198]


Table 5 Continued


32 Aliphatic aldehydes from olivefruit Antifungal and antielastase Active except

Candida spp Miconazole [180]

33 Table olives from Portugal Antioxidant andantimicrobial

Active exceptCandida spp

120572-Tocopherol TBHQampicillin andcycloheximide

[263]

34 Extracts of leaves fruits andseeds Antioxidant High Trolox [202]

35 Oleuropein hydroxytyrosoland tyrosol Antioxidant High Vitamin E BHT [185]

36 Long chain 120572 120573-unsaturatedaldehydes from olive fruit Antimicrobial Broad spectrum

activity mdash [166]

37 Phenolics from olive oil millwaste water Antioxidant Good

23-Tert-butyl-4-hydroxyanisole L-ascorbic

acid[192]

38 Maslinic acid Antioxidant Good Silymarin [193]39 EVOO Antioxidant Good Methyl linoleate [191]40 Phenolics Antioxidant Good Ascorbic acid [195]

evident antibacterial activity against species of ErwiniaClavibacterAgrobacterium and Pseudomonaswhile washingwaters from Spanish-style green olives were not so effect-ive These solutions also showed fungicidal activity againstspecies of Phytophthora Colletotrichum Alternaria Botrytisand Pestalotiopsis These activities were related to the glu-taraldehyde like compounds such as the dialdehydic formof decarboxymethyl elenolic acid in these solutions Thesefindings suggested that olive waste waters may be used inagriculture for pests management [178] Antifungal activitiesof aqueous acetone ethyl acetate and methanolic extracts ofolive leaves were investigated on 30 different fungal strainsusing disc diffusion method The aqueous extract showedthe highest activity and was active against 10 fungal strainsWhen sensitivity was compared Alternaria parasiticus wasthe most resistant strain while Alternaria wentii was themost sensitive one [179] A study was conducted to evaluatethe antifungal activity of some aliphatic aldehydes [hexanalnonanal (E)-2-hexenal (E)-2-heptenal (E)-2-octenal (E)-2-nonenal] from olive fruit against various strains ofTrichophy-ton mentagrophytes Microsporum canis and Candida sppThese compounds were also tested for their ability to inhibitelastase a virulence factor essential for the dermatophytesrsquocolonization The aldehydes showed a broad spectrum activ-ity and inhibited all the tested strains exceptCandida spp (E)-2-octenal and (E)-2-nonenal inhibited the elastase activity ina concentration dependent fashion [180] A similar type ofstudy has shown that volatiles from Tunisian olive cultivars(Chemlali and Neb Jmel) were found active against a numberof bacteria and fungi [181] Maslinic acid (104) a pentacyclictriterpenoid obtained from the pressed fruits of olives hasbeen studied against tachyzoites of Toxoplasma gondii Theparasite when treated with maslinic acid showed inhibitionof some of the proteases in a dose-dependent manner Thisprotease activity is required by the parasite for cell invasion

Hence maslinic acid can be a good agent to inhibit thisparasite [182] Micol et al described the antiviral activity of acommercial olive leaf extract (LExt) and its main constituentoleuropein against the viral hemorrhagic septicemia virus(VHSV) Both of these showed good activity against VHSVbefore infection as well as in postinfection treatment Boththe extracts were safe on health and environment so thesemay be used as promising natural antiviral agents [183]

44 Antioxidant Activities Reactive oxygen and nitrogenspecies are essential for energy supply chemical signalingdetoxification and immune function and are continuouslyproduced in the human body and their amount is carefullycontrolled under the action of endogenous enzymes such assuperoxide dismutase glutathione peroxidase and catalaseWith an overproduction of these reactive species an expo-sure to external oxidant substances or a failure in the defensemechanisms damage to valuable biomolecules (DNA lipidsproteins) may occur [26] This damage has been associatedwith an increased risk of cardiovascular disease cancer andother chronic diseases Hence antioxidants are requiredto prevent from oxidative damage and chronic diseases[184] Antioxidant activities of O europaea have been sum-marized in Table 5 Le Tutour and Guedon investigated theantioxidant activity of oleuropein hydroxytyrosol and tyro-sol from the leaves ofO europaea in comparisonwith vitaminE and BHT Oleuropein and hydroxytyrosol showed highantioxidant activity while tyrosol showed neither antioxidantnor prooxidant activity [185] Oleuropein was also evaluatedfor its antioxidant activity in vitro using chemiluminescenceassay and was found to have remarkable antioxidant activity[186] Later on Fogliano et al evaluated the antioxidant activi-ties of two virgin olive oils obtained from same olive batch butprocessed with different hammer crushing conditions andfound that the efficacy of the olive oil which was processedunder higher hammer crushing ratewas higher than the other


[187] In another study antioxidant activity of different phe-nolic compounds isolated from the leaves of O europaea wasdetermined These compounds included oleuropein verbas-coside luteolin-7-glucoside apigenin-7-glucoside diosme-tin-7-glucoside luteolin diosmetin rutin catechin tyrosolhydroxytyrosol vanillin vanillic acid and caffeic acidAmong these the flavonoids rutin luteolin and catechinshowed the highest activity against ABTS radicals [188]

Briante et al proposed a fast method for the biotrans-formation of the leaves extract of O europaea by a ther-mophilic 120573-glycosidase enzyme immobilized on chitosan toget extracts with high amounts of hydroxytyrosol To confirmthe transformation the resulting extracts were evaluated fortheir antioxidant activities in comparison with the originalolive leaves extract The resulting eluates showed a higherantioxidant activity than their extract of origin due to thepresence of a higher concentration of simple biophenols[189] A similar kind of comparative study was performedbetween extra virgin olive oils (EVOOs) of different degreesof degradation It was concluded that the EVOO with alow degradation level of 3101584041015840-DHPEA-EDA and a lowercontent of 3101584041015840-DHPEA than the oils with intermediate andadvanced degradation levels were 3ndash5 times more efficientas DPPH scavengers and 2 times more efficient as inhibitorsof the XOD-catalyzed reaction than oils with intermediateand advanced degradation levels [190] Similar studies havealso been carried out on EVOO showing that the compoundresponsible for the antioxidant properties of the EVOO was34-DHPEA-EDA [191] Ranalli et al elucidated the antiox-idizing potency of phenolics present in olive oil mill wastewaters using reference standards of natural and syntheticorigin commonly used as food preservatives The resultsshowed that many phenolics present in olive oil mill wastewater have good antioxidizing capacities and could replacesome less safe synthetic antioxidants used to preserve fooditems industrially [192] The effect of maslinic acid (104)obtained from olive pomace on the vulnerability of plasmamembrane to lipid peroxidation has been investigated bothin vitro and in vivo in rats It was concluded that maslinicacid may offer some resistance to oxidative stress in animals[193] LC-MS screening of freeze-dried olives from Italiancultivatorswas performed alongwith their antioxidant profileshowing differences in antioxidant behavior of olives ofdifferent cultivators [194] In a similar study the phenoliccomponents of O europaea were identified by HPLC andantioxidant activities of different isolates were measured insunflower oil by measuring peroxide values [195]

Antioxidant activities of different parts of O europaeahave been evaluated in different studies using hydroxyl and22-diphenyl-1-picrylhydrazyl (DPPH) radicals as referenceThese include olive leaves infusion [196] ethanolic extractof olive leaves [197 198] olive fruit and leaves [136 199]aqueous olive leaf extract [171 200] and olives from Dhokarolive cultivators [201] All the extracts exhibited very goodantioxidant activities The phenolic compounds composi-tion and antioxidant activities of table olives from differ-ent cultivators of Portugal namely Tras-os-Montes e AltoDouro Galega Negrinha de Freixo Azeitona de ConservaNegrinha de Freixo olives and Azeitona de Conserva de

Elvas e Campo Maior olives were examined using troloxas a reference All the extracts showed very good radicalscavenging activities which proved them to be a healthy dietsupplement [167 202] In a different study extra virgin oliveoils of different varieties including arbequina hojiblancaand picual were taken and their n-hexaneethanol (20 80)extracts were assessed for their radical scavenging activitiesusing DPPH (22-diphenyl-1-picrylhydrazyl) ABTS (221015840-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid)) hydroxylradical hydrogen peroxide and superoxide anion inhibitoryactivities The results indicated that EVOOs possess greaterantioxidant potential than pure olive oils [203] Tunisianolives were subjected to antioxidant assays using troloxequivalent antioxidant capacity (TEAC) protocol and werefound to have antioxidant capacity between 212 and 462120583MTEACg of dry weight [204]

Conde et al subjected O europaea pruning to liquid hotwater treatment (LHW) and steam explosion (SE) andnoticed that hot water treatment enhanced the release ofphenolic compounds in the aqueous phase Syringol and syr-ingaldehyde were among the most abundant volatile com-pounds and oleuropein hydroxytyrosol syringaldehyde andtyrosol were the most abundant phenolics identified byHPLC The extracts showed a promising antioxidant activitywhichwas hardly affected by the temperature of the treatment[205] Olive trees in Portugal were sprayed with differentcopper formulations in order to protect the trees fromdifferent fungal diseases Later on the leaves of those treeswere analyzed for their copper content by atomic absorptionspectrometry It was observed that the samples with morecopper content have a decreased level of phenolic compoundsand in turn less radical scavenging capacity [206]

Four major phenolic compounds present in olive oilnamely hydroxytyrosol (84) oleuropein (1) hydroxytyrosol-elenolate (14) and 34-dihydroxyphenylethanol-elenolic aciddialdehyde (39) were studied for their protective effect onRBCs against oxidative damage All four compounds signif-icantly showed the protective effect for RBCs from oxidativedamage in a dose-dependent manner [207] Abaza et al con-ducted a study to test the effect of extraction solvent onantioxidant activity Antioxidant activities were evaluatedusing DPPH and ABTS methods Results revealed thatmethanol is recommended for the extracts with high levelof flavonoids and antioxidant activities [208] The protectiveeffects of olive leaf extract on genotoxicity and oxidativedamage in cultured human blood cells are also studied Theolive leaf extract at all doses did not induce any significantchanges in genotoxicity however it increased total antiox-idant capacity in plasma in vitro The ethanol extract at100mgL dose induced genoprotective activity via increasein antioxidant activity scavenging of free radicals and inhi-bition of oxidative stress [209] The effect of ripening onthe antioxidant activities of the olive pericarp was examinedin eleven different olive cultivars grown in southern ItalyThe geranylgeranyl reductase transcript levels along withthe biophenols and tocopherols were studied and it wasobserved that an inverse relation exists between them Atripening stages of pericarp the tocopherol levels increasedgradually while biophenolic levels decreased significantly


confirming the significant properties of antioxidants in theripe olive drupes hence establishing their nutritional value[210] Antioxidant properties of phenolic compounds ofolive fruits pulp from chamlal variety were evaluated incomparison with vitamin C Hydrogen peroxide (H

2O2)

scavenging and iron reduction tests were performed todetermine the antioxidant activities All the tested substancesexhibited a strong reducing power The protective effect ofthe extracts against lipids and proteins peroxidation wasalso studied The olive pulp showed a significant activityfor the protection of lipids peroxidation [211] Petridis etal evaluated the antioxidant activities of fruits and leavesof eleven different olive cultivars and found that significantdifferences existed between the activities of different cultivarsand the oleuropein content and antioxidant activities of leaveswere higher than the fruits [212] The infusions of leaves ofO europaea from Mediterranean region were evaluated fortheir radical scavenging abilities usingDPPH radicals inmiceand were found good in reducing the oxidants in the body[196] The extracts of olive leaves have also been found to begood antioxidants against the oxidation of soybean oil undermicrowave heating Microwave heating causes severe nutri-tional and quality losses and increased the peroxide valuesOlive leaves extracts made availability of vitamin E in the testsamples ensuring protection against formation of peroxides[213] Machado et al studied the effect of irrigation andrain water on the growth total phenolic content antioxidantactivities and L-phenylalanine ammonia-lyase (PAL) activityof Portuguese olive tree cultivar CobrancosaThey found thatthe rain-fed olive trees during the maturation of their fruitsyielded in higher biophenolic content and PAL activity thanthe irrigated olive trees [214] An experiment was designedto study the effect of dietary olive leaves on lipid and proteinoxidation of refrigerated stored n-3 fatty acids-enriched porkIt was observed that the supplementation of meat witholive leaves decreased lipid oxidation but exerted no effecton protein oxidation in both raw and cooked meat [215]The hydroxyl-isochromans (81 and 82) were investigated fortheir antioxidant power and antiplatelet activity The resultssuggested them as very good antioxidants and inhibitors ofplatelet aggregation and thromboxane release so the use ofolive oil can reduce the risk of vascular diseases [216]

45 Enzyme Inhibition Activities The use of olive in folkmedicine to treat the inhibition of enzymes involved invarious ailments is old In Mediterranean folk medicinethe preparation of olive leaf has been used as a commontonic for gout [134] Flemmig et al investigated the possibleinhibitory effects of 80 ethanolic dry olive leaf extracts andnine isolated compounds from it against xanthine oxidase(XO) an enzyme which is a cause of gout Allopurinol wasused as a reference drug in this study Olive leaf extractas well as several of its phenolics showed xanthine oxidaseinhibitory activity The flavone apigenin (66) showed thestrongest XO inhibitory activity while oleuropein (1) caffeicacid (119) luteolin-7-O-120573-D-glucoside (64) and luteolin (68)also showed significant contribution in XO inhibition [134]Water extract of the fresh terminal branches of O europaeassp africana inhibited peptidase and glycosidase enzyme

activities which are produced by the periodontopathic bac-teria Porphyromonas gingivalis Bacteroides intermedius andTreponema denticola [217]The aqueous extract of olive leaveswas tested for Angiotensin Converting Enzyme (ACE) inhi-bition activity in vitro Due to significant activity a bioguidedisolation was performed to isolate the main componentresponsible for the ACE inhibition which was oleacein (39)while the other isolates did not show ACE inhibitory activity[96] A series of 120572120573-unsaturated aldehydes characterizedfrom olive oil flavor were found to inhibit the enzymetyrosinase which catalyzes the oxidation of L-34-dihydroxyphenylalanine (L-DOPA) These aldehydes were proved tobe noncompetitive inhibitors of tyrosinase and showed lowtoxicity on brine shrimp test [218]

46 Antihypertensive and Cardioprotective Activities Hyper-tension is the cause of heart diseases and it may causestroke of the arteries peripheral arterial diseases and chronickidney diseases if not treated Many natural products havebeen found effective against hypertension The cardiotoniceffects of three triterpenoids namely uvaol (102) ursolic acid(103) and oleanolic acid (105) isolated from the leaves of Oeuropaea were examined Oleanolic acid and uvaol showeda significant dose-response vasodepressor effect thereforeolive oil was suggested as a natural and cheap source ofcontrolling hypertension [219] A random parallel clinicaltrial was conducted on the patients of stage-1 hypertensionto evaluate the antihypertensive effects of olive leaf extractin comparison with the reference drug Captopril Olive leafextract was administered at a dose of 500mg twice a daywhile the control group was treated with 25mg Captopriltwice a day until 8 weeks All the patients showed a significantdecrease in their systolic as well as diastolic blood pressureafter treatment and the patients treated with olive leaf extractshowed better results than Captopril [220] Ethanolic extractof olive leaf upon injection intragastrically to mice at adose of 250mgKg body weight was found active against 11-deoxycorticosterone acetate induced hypertension [221] Inanother study the ethanolic or chloroform extract of oliveleaves showed a slow decrease in blood pressure in moderatehypertension after prolonged use [222] It was observedthat infusion of the dried olive leaves upon intravenousadministration to mice remained ineffective against normalblood pressure but had a decreasing effect in rennin and nore-pinephrine induced hypertension [223] The triterpenoidsisolated from the leaves ofO europaea from African Greeceand Cape Town cultivars were tested against insulin-resistantrats for hypertension at a dose of 60mgKg for six weeksTheresults showed that main active constituents were oleanolicacid and ursolic acid which prevented the hypertension andatherosclerosis and also improved the insulin resistance of thetest rats [224]

A clinical trial of aqueous extract of olive leaves wascarried out on hypertensive patients Patients were treatedwith 16120583gday olive leaves extract up to three months after15 days treatment based on placebo A significant decreasein their blood pressure was noticed after treatment withoutany side effects [225] In another study rats were treated for


Table 6 Antihypertensive activities of Olea europaea

S no Parttype of extractcompound Assay Activity Reference1 Uvaol ursolic acid and oleanolic acid Cardiotonic Good for uvaol and oleanolic acid [219]2 Leaf extract Antihypertensive Very good [220]3 Leaf extract In vivo studies Dose dependent [221]4 Leaves infusion In vivo studies Active on prolonged use [223]5 Oleanolic and ursolic acid In vivo studies in insulin resistant rats Active on 60mgKg dose [224]6 Leaf extract (EFLA 943) In vivo studies in rats Active on 100mgKg dose [264]

7 Leaf extract (EFLA 943) Studies in borderline hypertensivemonozygotic twins Good activity [227]

6 weeks with nitro-L-arginine methyl ester to create hyper-tension in them Then upon treatment of specially preparedolive leaves extract with a dose of 100mgKg up to further 6weeks a normalization in blood pressure was observed [226]An open study was conducted in Switzerland which included40 borderline hypertensive monozygotic twins One personfrom each pair was administered with 500mgday of oliveleaf extract (EFLA 943) while the other was given a dose of1000mgday The treatment was carried out for 8 weeks Asa result it was noticed that blood pressure was reduced inall persons with more significant decrease in those treatedwith high dose It was also noticed that cholesterol levels alsodecreased in all the treatments in a dose-dependent manner[227] A commercial olive leaf extract (OLE) was investigatedfor its Ca2+ channel antagonistic effects on isolated rabbithearts and cultured cardiomyocytes OLE caused a decreasein systolic left ventricular pressure and heart rate as wellas an increase in relative coronary flow in a concentrationdependent fashion In conclusion OLE suppressed the L-type calcium channel directly and reversibly [228] It wasfound that olive oil can significantly reduce the risk of strokeheart attacks stomach cancer and other heart diseases [11]Antihypertensive activities of O europaea have also beensummarized in Table 6

47 Anti-Inflammatory and Antinociceptive Activities Extravirgin olive oil has shown remarkable anti-inflammatoryactivity due to oleocanthal (140) a compound present inEVOO which has a strikingly similar profile to ibuprofena synthetic anti-inflammatory drug [229] Studies on anti-inflammatory and antinociceptive effects of OLE on maleWistar rats showed that OLE doses of 50ndash200mgKg producedose-dependent analgesic effects and intraperitoneal admin-istration of 200mgKg OLE caused significant decrease inpain responses in formalin test [230] The ethanolic and n-hexane extracts of olive fruits were investigated for theirin vivo anti-inflammatory and antinociceptive activities Foranti-inflammatory activity the carrageenan-induced hindpaw edema model was used and for the antinociceptiveactivity the hot plate test in mice was used The resultsrevealed that n-hexane extract showed activity at 400mgKgdosewhile ethanolic extract did not show a significant activity[136] A study was conducted to evaluate the traditionalmedicinal uses of olive leaves in Tunisia Intraperitonealadministration of essential oil of O europaea at doses of

100 200 and 300mgKg caused a significant reduction inacetic acid-induced abdominal constrictions and paw edemain mice [135] Eidi et al studied the anti-inflammatory andantinociceptive activities of olive oil to scientifically provethe use of olive oil as pain relieving in folk medicineThe antinociceptive activity was studied using hot plateformalin and writhing tests while acute anti-inflammatoryeffects of olive oil in mice were studied using xylene earedema test [231] Similar set of studies was also conductedto show the effects of maslinic acid (104) in acetic acid-induced writhing inflammatory phase of formalin-inducedpain and capsaicin-induced mechanical allodynia in mice[232] The results indicated that the olive oil only decreasedthe second phase of formalin-induced pain while it exhibitedantinociceptive activity against writhing-induced pain inmice by acetic acid In the xylene ear edema test olive oilshowed significant anti-inflammatory activity in the micewhile maslinic acid also showed antiallodynic effects [231232] Ursolic acid a triterpenoid from olive leaves has beenreviewed for its anti- and proinflammatory activities [233]Sahranavard et al studied both the anti-inflammatory andantinociceptive activities of aqueous and methanolic extractsof defatted olive fruit The results showed that both extractsdid not exhibit good analgesic activity in the first phase offormalin test whereas the methanolic and aqueous extractsinhibited the induced pain in the second phase of formalintest at doses of 600mgKg and 450mgKg respectively[234] Anti-inflammatory and antinociceptive activities ofOeuropaea have also been summarized in Table 7

48 Gastroprotective Activities A study was carried out tocheck the effect of olive leaf extract on the gastric defensesystem against experimentally induced gastric lesions byabsolute ethanol inmiceTheOLEwas administered at a doseof 40 80 and 120mgKg while the reference drug ranitidinewas given to the positive control at a dose of 50mgKgintragastrically The protective effect of both the OLE andranitidine was similar and in conclusion OLE possessedsignificant gastroprotective activity It was suggested that theactivity may be due to the antioxidants present in OLE [235]Arsic et al described the gastroprotective effect of olive oilextract in respect to its quercetin content The quercetincontent of the samplewas confirmedbyHPLCCold-restraintstress (CRS) induced rat gastric mucosa lesions test wasapplied to observe the gastroprotective effect of the sample


Table 7 Anti-inflammatory and antinociceptive activities of Olea europaea


1 Oleanolic acid Antinociceptive Female CD-1 mice(Barcelona Spain) mdash Ibuprofen pregabalin

baclofen [232]

2 Olive oil Antinociceptive andanti-inflammatory Male BalbC mice 10mgKg Dexamethasone [231]

3 n-Hexane extract offruits

Anti-inflammatory andantinociceptive

Male Swiss albinomice 400mgKg Indomethacin

acetylsalicylic acid [136]

4 Olive oil Analgesic and anti-inflammatory Male Wistar rats 100ndash300mgKg Acetyl salicylate of lysine [135]

5 n-Hexane extract offruit




6 Ethanolic extract ofdry leaves Antinociceptive antihyperalgesic Male Wistar rats 200mgKg Morphine [230]

7 EVOO Oleocanthal Ibuprofen like activity In vitro mdash Ibuprofen [229]

Olive oil extract showed gastroprotective activity close toquercetin one of the most studied flavonoid with antiulcerproperties [236] Aqueous extract of the dried olive leaveswas tested for its antiulcer effect in mice Upon intragastricadministration it was found effective antiulcer agent againstaspirin-induced gastric ulcers [237] Olive fruit pulp (OFP)is a rich source of antioxidants and possesses very good hep-atoprotective activity against CCl

4-induced hepatic damage

in mice [238]

49 Neuroprotective Activities It has been reported thatMediterranean diet has a healthy effect on its people andthey have a reduced risk of neurodegenerative [239] andcancer risks including breast and colon cancer [240 241]Guan et al investigated the effect of maslinic acid (104) atriterpenoid isolated from olive leaves on neuroprotectionin type 2 diabetic rats Streptozotocin was injected to induceneuronal death in mice Maslinic acid showed a signifi-cant neuroprotective activity in a dose-dependent manner[242] In another similar study the effect of maslinic acidwas observed on cultures of neurons from cerebral cortexThe results revealed that maslinic acid promoted a dose-dependent neuron survival during glutamate toxicity andmay be a lead for natural neuroprotective drugs [243] Qianet al studied the effect of maslinic acid and its mechanism ofaction on cortical neurons using oxygen-glucose deprivationand then reoxygenation of 24 hours Flow cytometry assaywas used to monitor neuronal apoptosis and the resultsshowed that maslinic acid alleviated the neuron injury in adose-dependent manner [244]

The olive leaf extract was investigated for diabetic neu-ropathic pain on in vitro and in vivo models Nerve growthfactor (NGF) treated PC-12 cells were used for in vitro studiesand streptozotocin-induced rat models were used for in vivostudies Immunoblotting assay was used for the evaluation ofneural apoptosis The results showed that olive leaf extractdecreased cell damage at a dose of 400120583gmL in NGF treatedcells OLE also showed potent DPPH radical scavengingactivity [245] Four groups of Wistar rats were studied forcerebral ischemia-reperfusion injury One group was treated

with distilled water and the other three groups were treatedorally with OLE at doses of 50 75 and 100mgKgdayAccording to the obtained results OLE reduced infarctvolume blood-brain barrier permeability brain edema andimproved neurologic deficit scores after transient middlecerebral artery occlusion (MCAO) [246] In Alzheimerrsquosdisease Tau aggregation into fibrillary tangles gives rise tointraneuronal lesions Daccache et al studied the ability ofhydroxytyrosol (84) oleuropein (1) and oleuropein aglycone(4) isolated from olives to prevent in vitro tau fibrillizationOleuropein was found to be even more active than thereference drug methylene blue on both wild-type and P301LTau proteins at low micromolar concentrations [247] OLEwas studied for its effect on brain lipidomics in rat strokemodel OLE was administered to male Wistar rats at doses of50 75 and 100mgKgday It increased the brain cholesterolester cholesterol cerebroside and phosphatidylcholine levelsand reduced the brain ceramide levels on all doses while itincreased the brain triglyceride levels only at doses of 75 and100mgKgday [248]

Parkinson disease is the most common neurodegenera-tive syndrome resulting in slow death of midbrain dopamin-ergic neurons Pasban-Aliabadi et al designed a study toobserve the effects of olive leaf extract and its main com-ponent oleuropein on 6-hydroxydopamine- (6-OHDA-)induced toxicity in rat adrenal pheochromocytoma (PC12)cells as an in vitro model of Parkinsonrsquos disease Incubationof these cells with olive leaf extract (400 and 600 120583gmL)and oleuropein (20 and 25 120583gmL) decreased cell damage andreduced biochemical markers of cell death Thus the resultssuggested the use of olive leaf extract and oleuropein in thetreatment of Parkinsonrsquos disease as well [249] Oleuropeinaglycone (4) prevented the formation of toxic amyloid aggre-gates in brain a characteristic feature of Alzheimerrsquos disease[250]

410 Miscellaneous Activities Diuretic activity of OLE hasbeen studied through determination of natriuretic salureticand carbonic anhydrase inhibition in lithium clearance


experiments According to the results the aqueous methano-lic and petroleum ether extracts of O europaea possessefficient diuretic activity [251] Wound healing activity ofn-hexane and aqueous extract of dried olive leaves wasobserved using in vivo wound models in comparison withthe reference drugMadecassolThe aqueous extract exhibitedgreater wound healing as well as antioxidant potential [252]To study the antileech effects of olive methanolic extract100 leeches (Limnatis nilotica) were treated with methanolicextract of olives in comparison with the reference drugsTinidazole and Levamisole Tinidazole showed no effect onkilling of leeches but Levamisole and olive extract killedleeches with a mean death time of 10 and 210 minutesrespectively [253] Sato et al studied antiallergic substances inolivewastematerials of three Japanese varieties ofO europaeanamed asMission Lucca andManzanilloThe results showedthat the antiallergic activity of 34-DHPEA-EA was greaterthan that of hydroxytyrosol and elenolic acid with an IC

50

value of 335 plusmn 06 120583gmL [254] A recent study suggestedthat virgin olive oil (VOO) reduced hypoxia-reoxygenationinjury in rat brain In that study 60maleWistar rats were usedand the effect of VOO on brain lipidomics during stroke wasstudied The results revealed that VOO pretreatment for 30days decreased the brain ceramide levels in doses of 05 and075mLKgday [255]

5 Toxicology

The effects of OLE on the hematology biochemistry kidneyand liver of Wistar male albino rats were determined toevaluate its toxicity profile Total 30 rats were included in thestudy and fed on the OLE for 6 weeks They were dividedinto five groups with group 1 being the control group (regulardiet without OLE) and the other four groups fed on 0204 07 and 09 respectively The factors that werestudied were lactate dehydrogenase (LDH) concentrations ofalkaline phosphatase (ALP) in serum cholesterol bilirubintriglycerides and glucose levels Groups 3 4 and 5 showeda significant increase in the total bilirubin and serum ALPlevels while cholesterol glucose and serum triglyceride levelswere decreased in these groups as compared to the controlgroup Group 5 was affected the most as its liver and kidneysshowed alterations in their tissues including necrosis ofhepatocytes and a slight hemorrhage So it was concluded thatOLE should be used with care especially when being usedat higher doses for longer periods of times as it may haveundesirable effects on liver and kidneys [256] Safety profile ofmaslinic acid (67) a compound isolated from the cuticle ofOeuropaea was assessed by oral administration of high dosesto mice It was observed that a single oral administration of1000mgKg to mice did not produce any adverse effects andupon administration of a daily dose of 50mgKg for 28 daysdid not produce any symptoms of toxicity [257]

6 Conclusion

The extensive literature survey revealed O europaea tobe a sacred and important medicinal plant used for the

treatment of stomach problems diabetes hypertension diar-rhea respiratory and urinary tract infections skin diseasesbacterial and fungal infections hemorrhoids rheumatismasthma and hair loss Pharmacological studies carried outon the fresh plant materials crude extracts and isolatedcomponents of O europaea provide a reasonable support forits various traditional uses Recent studies have been carriedout focusing on evaluation of the antidiabetic anticancerantimicrobial antifungal antiviral antioxidant antihyper-tensive gastroprotective anti-inflammatory antinociceptiveneuroprotective and cardioprotective activities Most of thementioned pharmacological studies were aimed at confirm-ing its traditional uses It has been found that some ofits traditional uses like antioxidant antidiabetic anticancerand so forth have extensively been explored by severalresearchers Most of the pharmacological studies carried outon O europaea have been conducted on crude extracts ofdifferent parts of the plant and very few pharmacologicalreports are present for pure compounds isolated from thetitle plant of which oleuropein maslinic acid oleanolic acidand so forth are the most abundant and notable Thus itis somehow difficult to reproduce the results of all thestudies and pinpoint the exact bioactive metabolites Hencethere is a further need of studying the pure isolates fortheir pharmacological properties Phytochemical researchcarried out on O europaea has led to the isolation of manyclasses of compounds like iridoids secoiridoids lignansbiophenols flavonoids flavone glycosides isochromans andterpenoids from less polar fractions but the polar fractionsthat is n-butanol and water soluble fractions still possess avast scope for further phytochemical studies The outcomeof already reported phytochemical studies should furtherexpand its therapeutic potential for further pharmacologicalstudies especially in vivo studies Hence some of the depictedinteresting biological activities of O europaea can be furtherproceeded to make use of them as a future therapy Theoutcome of the future research in the above-mentioned areaswill provide a convincing support for the future clinical useof O europaea in modern medicine

Conflict of Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgment

Muhammad Ali Hashmi acknowledges the funding fromHigher Education Commission of Pakistan for his PhDstudies

References

[1] F Grohmann ldquoOleaceaerdquo Flora of Pakistan vol 59 p 9 1981[2] A CronquistAn Integrated System of Classification of Flowering

Plants Columbia University Press 1981[3] A Bianco Studies in Natural Products Chemistry vol 32 Elsev-

ier Science Amsterdam The Netherlands 1990


[4] USDA ldquoNational Genetic Resources Programrdquo GermplasmResources Information Networkmdash(GRIN) 2003

[5] G Bartolini and R Petruccelli Classification Origin Diffusionand History of the Olive Food and Agriculture Organization ofthe United Nations Rome Italy 2002

[6] E Wallander and V A Albert ldquoPhylogeny and classification ofOleaceae based on rps16 and trnL-F sequence datardquo AmericanJournal of Botany vol 87 no 12 pp 1827ndash1841 2000

[7] J A Perez J M Hernandez J M Trujillo and H LopezldquoIridoids and secoiridoids from Oleaceaerdquo Studies in NaturalProducts Chemistry vol 32 pp 303ndash363 2005

[8] F Medail P Quezel G Besnard and B Khadari ldquoSystematicsecology and phylogeographic significance of Olea europaea Lssp maroccana (Greuter amp Burdet) P Vargas et al a relictualolive tree in South-west Moroccordquo Botanical Journal of theLinnean Society vol 137 no 3 pp 249ndash266 2001

[9] T Bracci M Busconi C Fogher and L Sebastiani ldquoMolecularstudies in olive (Olea europaea L) overview on DNA markersapplications and recent advances in genome analysisrdquo Plant CellReports vol 30 no 4 pp 449ndash462 2011

[10] D Kaniewski E van Campo T Boiy J-F Terral B Khadariand G Besnard ldquoPrimary domestication and early uses of theemblematic olive tree palaeobotanical historical andmolecularevidence from the Middle Eastrdquo Biological Reviews vol 87 no4 pp 885ndash899 2012

[11] M Sarwar ldquoThe theatrical usefulness of olive Olea europaeaL(Oleaceae family) nutrition in human health a reviewrdquo SkyJournal of Medicinal Plant Research vol 2 no 1 pp 1ndash4 2013

[12] D Zohary M Hopf and E Weiss Domestication of Plants inthe Old World The Origin and Spread of Domesticated Plants inSouthwest Asia Europe and the Mediterranean Basin OxfordUniversity Press Oxford UK 2012

[13] D Ryan and K Robards ldquoPhenolic compounds in olivesrdquoAnalyst vol 123 no 5 pp 31Rndash44R 1998

[14] P Kanakis A Termentzi T Michel E Gikas M Halabalakiand A-L Skaltsounis ldquoFrom olive drupes to olive Oil AnHPLC-orbitrap-based qualitative and quantitative explorationof olive keymetabolitesrdquoPlantaMedica vol 79 no 16 pp 1576ndash1587 2013

[15] G S Sibbett L Ferguson and M Lindstrand Olive ProductionManual University of California Department of Agricultureand Natural Resources 2005

[16] M Parras Rosa ldquoLa domanda di olii drsquoolivardquo Olivaelig vol 63 pp24ndash33 1996

[17] M Bonazzi ldquoEuro-Mediterranean policies and olive oil com-petition or job sharingrdquo Olivae vol 65 pp 16ndash20 1997

[18] A Bendini L Cerretani A Carrasco-Pancorbo et al ldquoPhenolicmolecules in virgin olive oils A survey of their sensory prop-erties health effects antioxidant activity and analytical meth-ods An overview of the last decaderdquo Molecules vol 12 no 8pp 1679ndash1719 2007

[19] E L Ghisalberti ldquoBiological and pharmacological activity ofnaturally occurring iridoids and secoiridoidsrdquo Phytomedicinevol 5 no 2 pp 147ndash163 1998

[20] C Soler-Rivas J C Espin and H J Wichers ldquoOleuropeinand related compoundsrdquo Journal of the Science of Food andAgriculture vol 80 no 7 pp 1013ndash1023 2000

[21] S H Omar ldquoOleuropein in olive and its pharmacologicaleffectsrdquo Scientia Pharmaceutica vol 78 no 2 pp 133ndash154 2010

[22] Z Erbay and F Icier ldquoThe importance and potential uses of oliveleavesrdquo Food Reviews International vol 26 no 4 pp 319ndash3342010

[23] C M Galanakis ldquoOlive fruit dietary fiber components recov-ery and applicationsrdquo Trends in Food Science amp Technology vol22 no 4 pp 175ndash184 2011

[24] H K Obied M S Allen D R Bedgood P D Prenzler KRobards and R Stockmann ldquoBioactivity and analysis of bio-phenols recovered from olivemill wasterdquo Journal of Agriculturaland Food Chemistry vol 53 no 4 pp 823ndash837 2005

[25] A Saija and N Uccella ldquoOlive biophenols functional effects onhuman wellbeingrdquo Trends in Food Science and Technology vol11 no 9-10 pp 357ndash363 2000

[26] S N El and S Karakaya ldquoOlive tree (Olea europaea) leavespotential beneficial effects on human healthrdquoNutrition Reviewsvol 67 no 11 pp 632ndash638 2009

[27] C M Kalua M S Allen D R Bedgood Jr A G Bishop P DPrenzler andK Robards ldquoOlive oil volatile compounds flavourdevelopment and quality a critical reviewrdquo Food Chemistry vol100 no 1 pp 273ndash286 2007

[28] Y Khan S Panchal N Vyas A Butani and V Kumar ldquoOleaeuropaea a phyto-pharmacological reviewrdquo PharmacognosyReviews vol 1 no 1 pp 114ndash118 2007

[29] S Cicerale X A Conlan A J Sinclair and R S J KeastldquoChemistry and health of olive oil phenolicsrdquo Critical Reviewsin Food Science and Nutrition vol 49 no 3 pp 218ndash236 2009

[30] S I Ali and Agricultural Research Council Flora of PakistanPakistan Agricultural Research Council 1982

[31] M X L Shu ldquoOleardquo Flora of China vol 15 pp 295ndash298 1996[32] R Ayerza and W Coates ldquoSupplemental pollinationmdashincreas-

ing olive (Olea europaea) yields in hot arid environmentsrdquoExperimental Agriculture vol 40 no 4 pp 481ndash491 2004

[33] G Besnard B Khadari P Villemur and A Berville ldquoCytoplas-mic male sterility in the olive (Olea europaea L)rdquo Theoreticaland Applied Genetics vol 100 no 7 pp 1018ndash1024 2000

[34] S Kumar T Kahlon and S Chaudhary ldquoA rapid screening foradulterants in olive oil using DNA barcodesrdquo Food Chemistryvol 127 no 3 pp 1335ndash1341 2011

[35] N Liphschitz R Gophna M Hartman and G Biger ldquoThebeginning of olive (Olea europaea) cultivation in the old worlda reassessmentrdquo Journal of Archaeological Science vol 18 no 4pp 441ndash453 1991

[36] E Gooch Ten Plus One Things You May Not Know about OliveEpikouria Magazine Triaina Publishers 2005

[37] E Galili D J Stanley J Sharvit andMWeinstein-Evron ldquoEvi-dence for earliest olive-oil production in submerged settlementsoff the Carmel Coast Israelrdquo Journal of Archaeological Sciencevol 24 no 12 pp 1141ndash1150 1997

[38] A Chiappetta and I Muzzalupo ldquoBotanical descriptionrdquo inOlive GermplasmmdashThe Olive Cultivation Table Olive and OliveOil Industry in Italy InTech 2012

[39] W E Wise Fray Junıpero Serra and the California ConquestScribner New York NY USA 1967

[40] G Besnard P Baradat and A Berville ldquoGenetic relationshipsin the olive (Olea europaea L) reflect multilocal selection ofcultivarsrdquoTheoretical and Applied Genetics vol 102 no 2-3 pp251ndash258 2001

[41] R Ghanbari F Anwar K M Alkharfy A-H Gilani and NSaari ldquoValuable nutrients and functional bioactives in differentparts of olive (Olea europaea L)mdasha reviewrdquo InternationalJournal of Molecular Sciences vol 13 no 3 pp 3291ndash3340 2012

[42] G Bartolini G Prevost C Messeri and G Carignani OliveGermplasm Cultivars and World-Wide Collections 1998


[43] T Ganino G Bartolini and A Fabbri ldquoThe classification ofolive germplasmmdasha reviewrdquo Journal ofHorticultural Science andBiotechnology vol 81 no 3 pp 319ndash334 2006

[44] H K Obied ldquoBiography of biophenols past present andfuturerdquo Functional Foods in Health and Disease vol 3 no 6 pp230ndash241 2013

[45] T Jerman P Trebse and BM Vodopivec ldquoUltrasound-assistedsolid liquid extraction (USLE) of olive fruit (Olea europaea)phenolic compoundsrdquo Food Chemistry vol 123 no 1 pp 175ndash182 2010

[46] H Tsukamoto S Hisada and S Nishibe ldquoLignans from bark ofthe Olea plants Irdquo Chemical and Pharmaceutical Bulletin vol32 no 7 pp 2730ndash2735 1984

[47] M Perez-Bonilla S Salido T A van Beek et al ldquoIsolation andidentification of radical scavengers in olive tree (Olea europaea)woodrdquo Journal of Chromatography A vol 1112 no 1-2 pp 311ndash318 2006

[48] H Tsukamoto S Hisada and S Nishibe ldquoCoumarin and sec-oiridoid glucosides from bark of Olea africana and Oleacapensisrdquo Chemical amp Pharmaceutical Bulletin vol 33 no 1 pp396ndash399 1985

[49] H Tsukamoto S Hisada S Nishibe and D G Roux ldquoPhenolicglucosides from Olea europaea subs africanardquo Phytochemistryvol 23 no 12 pp 2839ndash2841 1984

[50] H Tsukamoto S Hisada S Nishibe D G Roux and J PRourke ldquoCoumarins from Olea africana and Olea capensisrdquoPhytochemistry vol 23 no 3 pp 699ndash700 1984

[51] M Chiba K Okabe S Hisada K Shima T Takemoto and SNishibe ldquoElucidation of the structure of a new lignan glucosidefrom olea europaea by carbon-13 nuclear magnetic resonancespectroscopyrdquo Chemical amp Pharmaceutical Bulletin vol 27 no11 pp 2868ndash2873 1979

[52] A Bianco R L Scalzo and M L Scarpati ldquoIsolation of cor-noside from Olea europaea and its transformation into halleri-donerdquo Phytochemistry vol 32 no 2 pp 455ndash457 1993

[53] M Esti L Cinquanta and E La Notte ldquoPhenolic compoundsin different olive varietiesrdquo Journal of Agricultural and FoodChemistry vol 46 no 1 pp 32ndash35 1998

[54] A Bianco and N Uccella ldquoBiophenolic components of olivesrdquoFood Research International vol 33 no 6 pp 475ndash485 2000

[55] R W Owen R Haubner W Mier et al ldquoIsolation structureelucidation and antioxidant potential of the major phenolicand flavonoid compounds in brined olive drupesrdquo Food andChemical Toxicology vol 41 no 5 pp 703ndash717 2003

[56] A Peralbo-Molina F Priego-Capote and M D L de Cas-tro ldquoTentative identification of phenolic compounds in olivepomace extracts using liquid chromatography-tandem massspectrometry with a quadrupole-quadrupole-time-of-flightmass detectorrdquo Journal of Agricultural and Food Chemistry vol60 no 46 pp 11542ndash11550 2012

[57] M Savarese E de Marco and R Sacchi ldquoCharacterization ofphenolic extracts from olives (Olea europaea cv Pisciottana)by electrospray ionization mass spectrometryrdquo Food Chemistryvol 105 no 2 pp 761ndash770 2007

[58] A Bianco M A Chiacchio G Grassi D Iannazzo A PipernoandR Romeo ldquoPhenolic components ofOlea europea Isolationof new tyrosol and hydroxytyrosol derivativesrdquo Food Chemistryvol 95 no 4 pp 562ndash565 2006

[59] A Bianco C Melchioni A Ramunno G Romeo and NUccella ldquoPhenolic components of Olea europaeamdashisolation oftyrosol derivativesrdquo Natural Product Research vol 18 no 1 pp29ndash32 2004

[60] R Maestroduran R Leoncabello V Ruizgutierrez P Fiestasand A Vazquezroncero ldquoBitter phenolic glucosides from seedsof olive (Olea europaea)rdquoGrasas y Aceites vol 45 no 5 pp 332ndash335 1994

[61] L Bastoni A Bianco F Piccioni and N Uccella ldquoBiophenolicprofile in olives by nuclear magnetic resonancerdquo Food Chem-istry vol 73 no 2 pp 145ndash151 2001

[62] A Bianco F Buiarelli G P Cartoni F Coccioli R Jasionowskaand P Margherita ldquoAnalysis by liquid chromatography-tandemmass spectrometry of biophenolic compounds in olives andvegetation waters Part Irdquo Journal of Separation Science vol 26no 5 pp 409ndash416 2003

[63] A Bianco F Buiarelli G P Cartoni F Coccioli R Jasionowskaand P Margherita ldquoAnalysis by liquid chromatography-tandemmass spectrometry of biophenolic compounds in virgin oliveoil Part IIrdquo Journal of Separation Science vol 26 no 5 pp 417ndash424 2003

[64] G Bianchi and N Pozzi ldquo34-Dihydroxyphenylglycol a majorC6-C2phenolic inOlea europaea fruitsrdquo Phytochemistry vol 35

no 5 pp 1335ndash1337 1994[65] G Rodrıguez A Lama S Jaramillo et al ldquo34-Dihydroxy-

phenylglycol (DHPG) an important phenolic compoundpresent in natural table olivesrdquo Journal of Agricultural and FoodChemistry vol 57 no 14 pp 6298ndash6304 2009

[66] GVlahov C Schiavone andN Simone ldquoTriacylglycerols of theolive fruit (Olea europaea L) characterization of mesocarp andseed triacylglycerols in different cultivars by liquid chromatog-raphy and13C NMR spectroscopyrdquo Fett-Lipid vol 101 no 4 pp146ndash150 1999

[67] A Bianco RAMazzei CMelchioniM L Scarpati G Romeoand N Uccella ldquoMicrocomponents of olive oil Part II Digalac-tosyldiacylglycerols from Olea europaeardquo Food Chemistry vol62 no 3 pp 343ndash346 1998

[68] F Sakouhi C Absalon H Kallel and S Boukhchina ldquoCom-parative analysis of triacylglycerols fromOlea europaea L fruitsusing HPLC and MALDI-TOFMSrdquo European Journal of LipidScience and Technology vol 112 no 5 pp 574ndash579 2010

[69] C Marra andM E Giordano ldquoA new diacylglycerol from fresholive pulprdquo Natural Product Research vol 19 no 1 pp 81ndash852005

[70] A Procopio S Alcaro M Nardi et al ldquoSynthesis biologicalevaluation and molecular modeling of oleuropein and its sem-isynthetic derivatives as cyclooxygenase inhibitorsrdquo Journal ofAgricultural and Food Chemistry vol 57 no 23 pp 11161ndash111672009

[71] N Nenadis and M Z Tsimidou ldquoOleuropein and relatedsecoiridoids Antioxidant activity and sources other than Oleaeuropaea L (olive tree)rdquo in Recent Progress in Medicinal PlantsChemistry and Medicinal Value pp 53ndash74 Studium Press LLCHouston Tex USA 2009

[72] E Haloui B Marzouk Z Marzouk A Bouraoui and NFenina ldquoHydroxytyrosol and oleuropein from olive leavespotent anti-inflammatory and analgesic activitiesrdquo Journal ofFood Agriculture amp Environment vol 9 no 3-4 pp 128ndash1332011

[73] S M Cardoso S I Falcao A M Peres and M R MDomingues ldquoOleuropeinligstroside isomers and their deriva-tives in Portuguese olive mill wastewatersrdquo Food Chemistry vol129 no 2 pp 291ndash296 2011

[74] F Aouidi N Dupuy J Artaud et al ldquoRapid quantitativedetermination of oleuropein in olive leaves (Olea europaea)


using mid-infrared spectroscopy combined with chemometricanalysesrdquo Industrial Crops and Products vol 37 no 1 pp 292ndash297 2012

[75] R lo Scalzo and M L Scarpati ldquoA new secoiridoid from olivewastewatersrdquo Journal of Natural Products vol 56 no 4 pp 621ndash623 1993

[76] M Servili M Baldioli R Selvaggini A Macchioni and GMontedoro ldquoPhenolic compounds of olive fruit one- and two-dimensional nuclear magnetic resonance characterization ofnuzhenide and its distribution in the constitutive parts of fruitrdquoJournal of Agricultural and Food Chemistry vol 47 no 1 pp 12ndash18 1999

[77] L Gentile and N A Uccella ldquoSelected bioactives from calluscultures of olives (Olea europaea L Var Coratina) by LC-MSrdquoFood Research International vol 55 pp 128ndash136 2014

[78] F Paiva-Martins and M Pinto ldquoIsolation and characterizationof a new hydroxytyrosol derivative from olive (Olea europaea)leavesrdquo Journal of Agricultural and Food Chemistry vol 56 no14 pp 5582ndash5588 2008

[79] F Paiva-Martins V Rodrigues R Calheiros and M P MMarques ldquoCharacterization of antioxidant olive oil biophenolsby spectroscopic methodsrdquo Journal of the Science of Food andAgriculture vol 91 no 2 pp 309ndash314 2011

[80] M Bouaziz R J Grayer M S J Simmonds M Damak and SSayadi ldquoIdentification and antioxidant potential of flavonoidsand low molecular weight phenols in olive cultivar Chemlaligrowing in Tunisiardquo Journal of Agricultural and Food Chemistryvol 53 no 2 pp 236ndash241 2005

[81] J Meirinhos B M Silva P Valentao et al ldquoAnalysis andquantification of flavonoidic compounds from Portuguese olive(Olea europaea L) leaf cultivarsrdquoNatural Product Research vol19 no 2 pp 189ndash195 2005

[82] F Sakouhi C Absalon K Sebei E Fouquet S Boukhchinaand H Kallel ldquoGas chromatographic-mass spectrometric char-acterisation of triterpene alcohols and monomethylsterols indevelopingOlea europaea L fruitsrdquo Food Chemistry vol 116 no1 pp 345ndash350 2009

[83] A Guinda M Rada T Delgado P Gutierrez-Adanez and J MCastellano ldquoPentacyclic triterpenoids from olive fruit and leafrdquoJournal of Agricultural and Food Chemistry vol 58 no 17 pp9685ndash9691 2010

[84] M Gil A Haıdour and J L Ramos ldquoTwo glutaric acid deriv-atives from olivesrdquo Phytochemistry vol 49 no 5 pp 1311ndash13151998

[85] G Bianchi CMurelli andGVlahov ldquoSurface waxes fromolivefruitsrdquo Phytochemistry vol 31 no 10 pp 3503ndash3506 1992

[86] G Vlahov G Rinaldi P del Re andA A Giuliani ldquo 13Cnuclearmagnetic resonance spectroscopy for determining the differentcomponents of epicuticular waxes of olive fruit (Olea europaea)Dritta cultivarrdquoAnalytica Chimica Acta vol 624 no 2 pp 184ndash194 2008

[87] X-F Wang C Li Y-P Shi and D-L Di ldquoTwo new secoiridoidglycosides from the leaves of Olea europaea Lrdquo Journal of AsianNatural Products Research vol 11 no 11 pp 940ndash944 2009

[88] V N Golubev Z D Gusar and E S Mamedov ldquoTocopherols ofOlea europaeardquo Chemistry of Natural Compounds vol 23 no 1pp 119ndash120 1987

[89] S Gomez-Gonzalez J Ruiz-Jimenez F Priego-Capote and MD L de Castro ldquoQualitative and quantitative sugar profilingin olive fruits leaves and stems by gas chromatography-tan-demmass spectrometry (GC-MSMS) after ultrasound-assisted

leachingrdquo Journal of Agricultural and Food Chemistry vol 58no 23 pp 12292ndash12299 2010

[90] D Ryan K Robards P Prenzler D Jardine T Herlt and MAntolovich ldquoLiquid chromatography with electrospray ionisa-tionmass spectrometric detection of phenolic compounds fromOlea europaeardquo Journal of Chromatography A vol 855 no 2 pp529ndash537 1999

[91] C Savournin B Baghdikian R Elias F Dargouth-KesraouiK Boukef and G Balansard ldquoRapid high-performance liquidchromatography analysis for the quantitative determination ofoleuropein in Olea europaea leavesrdquo Journal of Agricultural andFood Chemistry vol 49 no 2 pp 618ndash621 2001

[92] S Charoenprasert and A Mitchell ldquoFactors influencing phe-nolic compounds in table olives (Olea europaea)rdquo Journal ofAgricultural and Food Chemistry vol 60 no 29 pp 7081ndash70952012

[93] H Kuwajima T Uemura K Takaishi K Inoue andH InouyetldquoA secoiridoid glucoside from Olea europaeardquo Phytochemistryvol 27 no 6 pp 1757ndash1759 1988

[94] A Karioti A Chatzopoulou A R Bilia G Liakopoulos SStavrianakou and H Skaltsa ldquoNovel secoiridoid glucosides inOlea europaea leaves suffering from boron deficiencyrdquo Bio-science Biotechnology and Biochemistry vol 70 no 8 pp 1898ndash1903 2006

[95] P Gariboldi G Jommi and L Verotta ldquoSecoiridoids fromOleaeuropaeardquo Phytochemistry vol 25 no 4 pp 865ndash869 1986

[96] K Hansen A Adsersen S B Christensen S R Jensen UNyman andUW Smitt ldquoIsolation of an angiotensin convertingenzyme (ACE) inhibitor from Olea europaea and Olea lanceardquoPhytomedicine vol 2 no 4 pp 319ndash325 1996

[97] P Mussini F Orsini and F Pelizzoni ldquoTriterpenes in leaves ofOlea europaeardquo Phytochemistry vol 14 no 4 p 1135 1975

[98] I S Movsumov and A M Aliev ldquoOleanolic and maslinic acidsof the fruit ofOlea europaeardquoChemistry of Natural Compoundsvol 21 no 1 pp 125ndash126 1985

[99] N Sultana and A Ata ldquoOleanolic acid and related derivatives asmedicinally important compoundsrdquo Journal of Enzyme Inhibi-tion and Medicinal Chemistry vol 23 no 6 pp 739ndash756 2008

[100] E Komaki S Yamaguchi I Maru et al ldquoIdentification of anti-120572-amylase components from olive leaf extractsrdquo Food Scienceand Technology Research vol 9 no 1 pp 35ndash39 2003

[101] E Duquesnoy V Castola and J Casanova ldquoTriterpenes in thehexane extract of leaves ofOlea europaea L analysis using 13C-NMR spectroscopyrdquo Phytochemical Analysis vol 18 no 4 pp347ndash353 2007

[102] C Romero A Garcıa E Medina M V Ruız-Mendez A deCastro and M Brenes ldquoTriterpenic acids in table olivesrdquo FoodChemistry vol 118 no 3 pp 670ndash674 2010

[103] I S Movsumov ldquoComponents of the leaves of Olea verrucosardquoChemistry of Natural Compounds vol 30 no 5 p 626 1994

[104] G Bianchi N Pozzi and G Vlahov ldquoPentacyclic triterpeneacids in olivesrdquo Phytochemistry vol 37 no 1 pp 205ndash207 1994

[105] B Schumacher S Scholle J Holzl N Khudeir S Hess and CE Muller ldquoLignans isolated from Valerian identification andcharacterization of a new olivil derivative with partial agonisticactivity at A1 adenosine receptorsrdquo Journal of Natural Productsvol 65 no 10 pp 1479ndash1485 2002

[106] E Campeol G Flamini P L Cioni I Morelli F DrsquoAndreaand R Cremonini ldquo15-Anhydroxylitol from leaves of Oleaeuropaeardquo Carbohydrate Research vol 339 no 16 pp 2731ndash2732 2004


[107] F Paiva-Martins and M H Gordon ldquoIsolation and charac-terization of the antioxidant component 34-dihydroxyphen-ylethyl 4-formyl-3-formylmethyl-4-hexenoate from olive (Oleaeuropaea) leavesrdquo Journal of Agricultural and Food Chemistryvol 49 no 9 pp 4214ndash4219 2001

[108] A Guinda A Lanzon J J Rios and T Albi ldquoThe isolationand quantification of the components from olive leaf hexaneextractrdquo Grasas y Aceites vol 53 no 4 pp 419ndash422 2002

[109] S Cicerale L Lucas and R Keast ldquoBiological activities ofphenolic compounds present in virgin olive oilrdquo InternationalJournal of Molecular Sciences vol 11 no 2 pp 458ndash479 2010

[110] S Christophoridou P Dais L I-H Tseng and M SpraulldquoSeparation and identification of phenolic compounds in oliveoil by coupling high-performance liquid chromatography withpostcolumn solid-phase extraction to nuclear magnetic reso-nance spectroscopy (LC-SPE-NMR)rdquo Journal of Agriculturaland Food Chemistry vol 53 no 12 pp 4667ndash4679 2005

[111] M Perez-Trujillo AMGomez-Caravaca A Segura-CarreteroA Fernandez-Gutierrez and T Parella ldquoSeparation and iden-tification of phenolic compounds of extra virgin olive oil fromOlea Europaea L byHPLC-DAD-SPE-NMRMS Identificationof a new diastereoisomer of the aldehydic form of oleuropeinaglyconerdquo Journal of Agricultural and Food Chemistry vol 58no 16 pp 9129ndash9136 2010

[112] G Rodrıguez A Lama M Trujillo J L Espartero and JFernandez-Bolanos ldquoIsolation of a powerful antioxidant fromOlea europaea fruit-mill waste 34-DihydroxyphenylglycolrdquoLWTmdashFood Science and Technology vol 42 no 2 pp 483ndash4902009

[113] G Montedoro M Servili M Baldioli R Selvaggini E Miniatiand A Macchioni ldquoSimple and hydrolyzable compounds invirgin olive oil 3 Spectroscopic characterizations of the secoiri-doid derivativesrdquo Journal of Agricultural and Food Chemistryvol 41 no 11 pp 2228ndash2234 1993

[114] M Brenes F J Hidalgo A Garcıa et al ldquoPinoresinol and 1-acetoxypinoresinol two new phenolic compounds identified inolive oilrdquo Journal of the American Oil Chemistsrsquo Society vol 77no 7 pp 715ndash720 2000

[115] A Bianco F Coccioli M Guiso andCMarra ldquoThe occurrencein olive oil of a new class of phenolic compounds hydroxy-isochromansrdquo Food Chemistry vol 77 no 4 pp 405ndash411 2002

[116] M Perez-Bonilla S Salido T A van Beek et al ldquoIsolation ofantioxidative secoiridoids from olive wood (Olea europaea L)guided by on-line HPLC-DAD-radical scavenging detectionrdquoFood Chemistry vol 124 no 1 pp 36ndash41 2011

[117] I Khlif K Hamden M Damak and N Allouche ldquoA newtriterpene from Olea europea stem with antidiabetic activityrdquoChemistry of Natural Compounds vol 48 no 5 pp 799ndash8022012

[118] S Al-Khalil ldquoA survey of plants used in Jordanian traditionalmedicinerdquo Pharmaceutical Biology vol 33 no 4 pp 317ndash3231995

[119] J Bellakhdar R Claisse J Fleurentin and C Younos ldquoReper-tory of standard herbal drugs in the Moroccan pharmacopoeardquoJournal of Ethnopharmacology vol 35 no 2 pp 123ndash143 1991

[120] A Zargari ldquoIranian medicinal plantsrdquo Tehran University Publi-cations vol 3 p 392 1997

[121] V Darias S Abdala D Martin and F Ramos ldquoHypoglycaemicplants from the Canary Islandsrdquo Phytotherapy Research vol 10no 1 pp S3ndashS5 1996

[122] V Darias L Bravo E Barquin D M Herrera and C FraileldquoContribution to the ethnopharmacological study of theCanary

Islandsrdquo Journal of Ethnopharmacology vol 15 no 2 pp 169ndash193 1986

[123] J O Kokwaro Medicinal Plants of East Africa University ofNairobi Press 2009

[124] G Lawrendiadis ldquoContribution to the knowledge of the medic-inal plants of Greecerdquo Planta Medica vol 9 no 2 pp 164ndash1691961

[125] V De Feo R Aquino A Menghini E Ramundo and F Sen-atore ldquoTraditional phytotherapy in the Peninsula SorrentinaCampania southern Italyrdquo Journal of Ethnopharmacology vol36 no 2 pp 113ndash125 1992

[126] A PieroniDHeimler L Pieters B vanPoel andA J VlietinckldquoIn vitro anti-complementary activity of flavonoids from olive(Olea europaea L) leavesrdquo Pharmazie vol 51 no 10 pp 765ndash768 1996

[127] P Gastaldo ldquoOfficial compendium of the Italian flora XVIrdquoFitoterapia vol 45 pp 199ndash217 1974

[128] V de Feo and F Senatore ldquoMedicinal plants and phytotherapyin the Amalfitan Coast Salerno Province Campania SouthernItalyrdquo Journal of Ethnopharmacology vol 39 no 1 pp 39ndash511993

[129] J Giordano and P Levine ldquoBotanical preparations used inItalian folk medicine possible pharmacological and chemicalbasis of effectrdquo Social Pharmacology vol 3 no 1-2 pp 83ndash1101989

[130] S A Vardanian ldquoPhytotherapy of bronchial asthma inmedievalArmenian medicinerdquo Terapevticheskiı Arkhiv vol 50 no 4 pp133ndash136 1978

[131] R A Ribeiro de F de Barros M Margarida et al ldquoAcutediuretic effects in conscious rats produced by some medicinalplants used in the state of Sao Paulo Brasilrdquo Journal of Eth-nopharmacology vol 24 no 1 pp 19ndash29 1988

[132] S A Ghazanfar and A M Al-Al-Sabahi ldquoMedicinal plants ofNorthern and Central Oman (Arabia)rdquo Economic Botany vol47 no 1 pp 89ndash98 1993

[133] T Fujita E Sezik M Tabata et al ldquoTraditional medicinein Turkey VII Folk medicine in middle and west Black Searegionsrdquo Economic Botany vol 49 no 4 pp 406ndash422 1995

[134] J Flemmig K Kuchta J Arnhold and H W Rauwald ldquoOleaeuropaea leaf (PhEur) extract as well as several of its isolatedphenolics inhibit the gout-related enzyme xanthine oxidaserdquoPhytomedicine vol 18 no 7 pp 561ndash566 2011

[135] E Haloui Z Marzouk B Marzouk I Bouftira A Bouraouiand N Fenina ldquoPharmacological activities and chemical com-position of theOlea europaea L leaf essential oils from TunisiardquoJournal of Food Agriculture and Environment vol 8 no 2 pp204ndash208 2010

[136] I P Suntar E K Akkol and T Baykal ldquoAssessment of anti-inflammatory and antinociceptive activities of Olea europaeaLrdquo Journal of Medicinal Food vol 13 no 2 pp 352ndash356 2010

[137] J Guerin andH Reveillere ldquoAntifungal activity of plant extractsused in therapy 2 Study of 40 plant extracts against 9 fungispeciesrdquo in Annales Pharmaceutiques Francaises pp 77ndash81Masson Editeur Paris France 1985

[138] A Tahraoui J El-Hilaly Z H Israili and B Lyoussi ldquoEthno-pharmacological survey of plants used in the traditional treat-ment of hypertension and diabetes in south-eastern Morocco(Errachidia province)rdquo Journal of Ethnopharmacology vol 110no 1 pp 105ndash117 2007

[139] A Sheth K Mitaliya and S JoshiTheHerbs of Ayurveda Shet2005


[140] M S Ali-Shtayeh R M Jamous and R M Jamous ldquoCom-plementary and alternative medicine use amongst Palestiniandiabetic patientsrdquoComplementaryTherapies in Clinical Practicevol 18 no 1 pp 16ndash21 2012

[141] F J Alarcon-Aguilara R Roman-Ramos S Perez-GutierrezA Aguilar-Contreras C C Contreras-Weber and J L Flores-Saenz ldquoStudy of the anti-hyperglycemic effect of plants used asantidiabeticsrdquo Journal of Ethnopharmacology vol 61 no 2 pp101ndash110 1998

[142] B Amel ldquoTraditional treatment of high blood pressure anddiabetes in Souk Ahras districtrdquo Journal of Pharmacognosy andPhytotherapy vol 5 no 1 pp 12ndash20 2013

[143] H F Al-Azzawie and M-S S Alhamdani ldquoHypoglycemic andantioxidant effect of oleuropein in alloxan-diabetic rabbitsrdquo LifeSciences vol 78 no 12 pp 1371ndash1377 2006

[144] H Sato C Genet A Strehle et al ldquoAnti-hyperglycemic activityof a TGR5 agonist isolated from Olea europaeardquo Biochemicaland Biophysical Research Communications vol 362 no 4 pp793ndash798 2007

[145] H Jemai A E L Feki and S Sayadi ldquoAntidiabetic and anti-oxidant effects of hydroxytyrosol and oleuropein from oliveleaves in alloxan-diabetic ratsrdquo Journal of Agricultural and FoodChemistry vol 57 no 19 pp 8798ndash8804 2009

[146] A Eidi M Eidi and R Darzi ldquoAntidiabetic effect of Oleaeuropaea L in normal and diabetic ratsrdquo Phytotherapy Researchvol 23 no 3 pp 347ndash350 2009

[147] A Cumaoglu L Rackova M Stefek M Kartal P Maechlerand C Karasu ldquoEffects of olive leaf polyphenols against H

2O2

toxicity in insulin secreting 120573-cellsrdquo Acta Biochimica Polonicavol 58 no 1 pp 45ndash50 2011

[148] B Barbaro G Toietta R Maggio et al ldquoEffects of the olive-derived polyphenol oleuropein on human healthrdquo InternationalJournal of Molecular Sciences vol 15 no 10 pp 18508ndash185242014

[149] V K Dubey C R Patil S M Kamble et al ldquoOleanolic acidprevents progression of streptozotocin induced diabetic neph-ropathy and protects renal microstructures in Sprague Dawleyratsrdquo Journal of Pharmacology amp Pharmacotherapeutics vol 4no 1 pp 47ndash52 2013

[150] A A Al-Qarawi M A Al-Damegh and S A ElMougy ldquoEffectof freeze dried extract ofOlea europaea on the pituitary-thyroidaxis in ratsrdquo Phytotherapy Research vol 16 no 3 pp 286ndash2872002

[151] M de Bock J G B Derraik C M Brennan et al ldquoOlive(Olea europaea L) leaf polyphenols improve insulin sensitiv-ity in middle-aged overweight men a randomized placebo-controlled crossover trialrdquo PLoS ONE vol 8 no 3 Article IDe57622 2013

[152] I Casaburi F Puoci A Chimento et al ldquoPotential of oliveoil phenols as chemopreventive and therapeutic agents againstcancer a review of in vitro studiesrdquoMolecular Nutrition amp FoodResearch vol 57 no 1 pp 71ndash83 2013

[153] M E Juan UWenzel H Daniel and JM Planas ldquoErythrodiola natural triterpenoid from olives has antiproliferative andapoptotic activity in HT-29 human adenocarcinoma cellsrdquoMolecular Nutrition and Food Research vol 52 no 5 pp 595ndash599 2008

[154] V Goulas V Exarchou A N Troganis et al ldquoPhytochemicalsin olive-leaf extracts and their antiproliferative activity againstcancer and endothelial cellsrdquo Molecular Nutrition and FoodResearch vol 53 no 5 pp 600ndash608 2009

[155] Y Allouche F Warleta M Campos et al ldquoAntioxidant anti-proliferative and pro-apoptotic capacities of pentacyclic triter-penes found in the skin of olives onMCF-7 humanbreast cancercells and their effects on DNA damagerdquo Journal of Agriculturaland Food Chemistry vol 59 no 1 pp 121ndash130 2011

[156] R Fares S Bazzi S E Baydoun and R M Abdel-Massih ldquoTheantioxidant and anti-proliferative activity of the Lebanese Oleaeuropaea extractrdquo Plant Foods for Human Nutrition vol 66 no1 pp 58ndash63 2011

[157] X Wang H Bai X Zhang et al ldquoInhibitory effect of oleanolicacid on hepatocellular carcinoma via ERK-p53-mediated cellcycle arrest and mitochondrial-dependent apoptosisrdquo Carcino-genesis vol 34 no 6 pp 1323ndash1330 2013

[158] S Burattini S Salucci V Baldassarri et al ldquoAnti-apoptoticactivity of hydroxytyrosol and hydroxytyrosyl lauraterdquo Foodand Chemical Toxicology vol 55 pp 248ndash256 2013

[159] SMilanizadehM R Bigdeli B Rasoulian andD Amani ldquoTheeffects of olive leaf extract on antioxidant enzymes activity andtumor growth in breast cancerrdquo Thrita vol 3 no 1 Article IDe12914 2014

[160] F J Reyes-Zurita E E Rufino-Palomares J A Lupianez andM Cascante ldquoMaslinic acid a natural triterpene from Oleaeuropaea L induces apoptosis in HT29 human colon-cancercells via the mitochondrial apoptotic pathwayrdquo Cancer Lettersvol 273 no 1 pp 44ndash54 2009

[161] E E Rufino-Palomares F J Reyes-Zurita L Garcıa-Salguero etal ldquoMaslinic acid a triterpenic anti-tumoural agent interfereswith cytoskeleton protein expression in HT29 human colon-cancer cellsrdquo Journal of Proteomics vol 83 pp 15ndash25 2013

[162] F J Reyes J J Centelles J A Lupianez and M Cascanteldquo(21205723120573)-23-Dihydroxyolean-12-en-28-oic acid a new naturaltriterpene fromOlea europea induces caspase dependent apop-tosis selectively in colon adenocarcinoma cellsrdquo FEBS Lettersvol 580 no 27 pp 6302ndash6310 2006

[163] A Cardeno M Sanchez-Hidalgo M A Rosillo and C Ade la Lastra ldquoOleuropein a secoiridoid derived from olivetree inhibits the proliferation of human colorectal cancer cellthrough downregulation of HIF-1120572rdquo Nutrition and Cancer vol65 no 1 pp 147ndash156 2013

[164] A M Randon and E Attard ldquoThe in vitro immunomodula-tory activity of oleuropein a secoiridoid glycoside from Oleaeuropaea LrdquoNatural Product Communications vol 2 no 5 pp515ndash519 2007

[165] M Adnan R Bibi S Mussarat A Tariq and Z K Shin-wari ldquoEthnomedicinal and phytochemical review of Pakistanimedicinal plants used as antibacterial agents against Escherichiacolirdquo Annals of Clinical Microbiology and Antimicrobials vol 13no 1 article 40 2014

[166] A Kubo C S Lunde and I Kubo ldquoAntimicrobial activity ofthe olive oil flavor compoundsrdquo Journal of Agricultural and FoodChemistry vol 43 no 6 pp 1629ndash1633 1995

[167] A P Pereira I C F R Ferreira F Marcelino et al ldquoPhenoliccompounds and antimicrobial activity of olive (Olea europaeaL Cv Cobrancosa) leavesrdquo Molecules vol 12 no 5 pp 1153ndash1162 2007

[168] E Medina M Brenes C Romero A Garcıa and A de CastroldquoMain antimicrobial compounds in table olivesrdquo Journal ofAgricultural and Food Chemistry vol 55 no 24 pp 9817ndash98232007

[169] A Alkofahi R Batshoun W Owais and N Najib ldquoBiologicalactivity of some Jordanian medicinal plant extracts Part IIrdquoFitoterapia vol 68 no 2 pp 163ndash168 1997


[170] A N Sudjana C DrsquoOrazio V Ryan et al ldquoAntimicrobial activ-ity of commercial Olea europaea (olive) leaf extractrdquo Interna-tional Journal of Antimicrobial Agents vol 33 no 5 pp 461ndash4632009

[171] K-W Ko H J Kang and B Y Lee ldquoAntioxidant antimicrobialand antiproliferative activities of olive (Olea europaea L) LeafExtractsrdquo Food Science and Biotechnology vol 18 no 3 pp 818ndash821 2009

[172] M Korukluoglu Y Sahan A Yigit E T Ozer and S GucerldquoAntibacterial activity and chemical constitutions of Oleaeuropaea L leaf extractsrdquo Journal of Food Processing and Pres-ervation vol 34 no 3 pp 383ndash396 2010

[173] O-H Lee and B-Y Lee ldquoAntioxidant and antimicrobial activi-ties of individual and combined phenolics inOlea europaea leafextractrdquo Bioresource Technology vol 101 no 10 pp 3751ndash37542010

[174] D Keskin N Ceyhan A Ugur andADDbeys ldquoAntimicrobialactivity and chemical constitutions of West Anatolian olive(Olea europaea L) leavesrdquo Journal of Food Agriculture ampEnvironment vol 10 no 2 pp 99ndash102 2012

[175] F Brahmi G Flamini M Issaoui et al ldquoChemical compositionand biological activities of volatile fractions from three Tunisiancultivars of olive leavesrdquo Medicinal Chemistry Research vol 21no 10 pp 2863ndash2872 2012

[176] A A Zaki M I Shaaban N E Hashish M A Amer andM-F Lahloub ldquoAssessment of anti-quorum sensing activity forsome ornamental andmedicinal plants native to Egyptrdquo ScientiaPharmaceutica vol 81 no 1 pp 251ndash258 2013

[177] E Medina C Romero B de Los Santos et al ldquoAntimicrobialactivity of olive solutions from stored alpeorujo against plantpathogenic microorganismsrdquo Journal of Agricultural and FoodChemistry vol 59 no 13 pp 6927ndash6932 2011

[178] M Brenes A Garcıa B de los Santos et al ldquoOlive glutar-aldehyde-like compounds against plant pathogenic bacteria andfungirdquo Food Chemistry vol 125 no 4 pp 1262ndash1266 2011

[179] M Korukluoglu Y Sahan and A Yigit ldquoAntifungal propertiesof olive leaf extracts and their phenolic compoundsrdquo Journal ofFood Safety vol 28 no 1 pp 76ndash87 2008

[180] L Battinelli C Daniele M Cristiani G Bisignano A Saijaand G Mazzanti ldquoIn vitro antifungal and anti-elastase activityof some aliphatic aldehydes from Olea europaea L fruitrdquoPhytomedicine vol 13 no 8 pp 558ndash563 2006

[181] F Brahmi S Dabbou G Flamini H Edziri M Mastouri andM Hammami ldquoFatty acid composition and biological activitiesof volatiles from fruits of two Tunisian olive cultivarsrdquo Interna-tional Journal of Food Science amp Technology vol 46 no 6 pp1316ndash1322 2011

[182] L M de Pablos G Gonzalez R Rodrigues A G GranadosA Parra and A Osuna ldquoAction of a pentacyclic triterpenoidmaslinic acid against Toxoplasma gondiirdquo Journal of NaturalProducts vol 73 no 5 pp 831ndash834 2010

[183] V Micol N Caturla L Perez-Fons V Mas L Perez andA Estepa ldquoThe olive leaf extract exhibits antiviral activityagainst viral haemorrhagic septicaemia rhabdovirus (VHSV)rdquoAntiviral Research vol 66 no 2-3 pp 129ndash136 2005

[184] C Nasopoulou H C Karantonis M Detopoulou C ADemopoulos and I Zabetakis ldquoExploiting the anti-inflam-matory properties of olive (Olea europaea) in the sustainableproduction of functional food and neutraceuticalsrdquo Phytochem-istry Reviews vol 13 pp 445ndash458 2014

[185] B Le Tutour and D Guedon ldquoAntioxidative activities of Oleaeuropaea leaves and related phenolic compoundsrdquo Phytochem-istry vol 31 no 4 pp 1173ndash1178 1992

[186] E Speroni M C Guerra A Minghetti et al ldquoOleuropeinevaluated in vitro and in vivo as an antioxidantrdquo PhytotherapyResearch vol 12 pp S98ndashS100 1998

[187] V Fogliano A Ritieni S M Monti et al ldquoAntioxidant activityof virgin olive oil phenolic compounds in a micellar systemrdquoJournal of the Science of Food and Agriculture vol 79 no 13 pp1803ndash1808 1999

[188] O Benavente-Garcıa J Castillo J Lorente A Ortuno and J ADel Rio ldquoAntioxidant activity of phenolics extracted from Oleaeuropaea L leavesrdquo Food Chemistry vol 68 no 4 pp 457ndash4622000

[189] R Briante M Patumi S Terenziani E Bismuto F Febbraioand R Nucci ldquoOlea europaea L leaf extract and derivativesantioxidant propertiesrdquo Journal of Agricultural and Food Chem-istry vol 50 no 17 pp 4934ndash4940 2002

[190] V Lavelli ldquoComparison of the antioxidant activities of extravirgin olive oilsrdquo Journal of Agricultural and Food Chemistryvol 50 no 26 pp 7704ndash7708 2002

[191] J-R Morello S Vuorela M-P Romero M-J Motilva andM Heinonen ldquoAntioxidant activity of olive pulp and oliveoil phenolic compounds of the arbequina cultivarrdquo Journal ofAgricultural and Food Chemistry vol 53 no 6 pp 2002ndash20082005

[192] A Ranalli L Lucera and S Contento ldquoAntioxidizing potencyof phenol compounds in olive oil mill wastewaterrdquo Journal ofAgricultural and Food Chemistry vol 51 no 26 pp 7636ndash76412003

[193] M P Montilla A Agil M C Navarro et al ldquoAntioxidantactivity of maslinic acid a triterpene derivative obtained fromOlea europaeardquo PlantaMedica vol 69 no 5 pp 472ndash474 2003

[194] G Sivakumar C Briccoli Bati and N Uccella ldquoHPLC-MSscreening of the antioxidant profile of Italian olive cultivarsrdquoChemistry of Natural Compounds vol 41 no 5 pp 588ndash5912005

[195] M Skerget P Kotnik M Hadolin A R Hras M Simonic andZ Knez ldquoPhenols proanthocyanidins flavones and flavonolsin some plant materials and their antioxidant activitiesrdquo FoodChemistry vol 89 no 2 pp 191ndash198 2005

[196] S Goncalves D Gomes P Costa and A Romano ldquoThephenolic content and antioxidant activity of infusions fromMediterraneanmedicinal plantsrdquo Industrial Crops and Productsvol 43 no 1 pp 465ndash471 2013

[197] T-I Lafka A Lazou V Sinanoglou and E Lazos ldquoPhenolicextracts from wild olive leaves and their potential as edible oilsantioxidantsrdquo Foods vol 2 no 1 pp 18ndash31 2013

[198] RGMarwahMO Fatope R AMahrooqi G BVarmaHAAbadi and S K S Al-Burtamani ldquoAntioxidant capacity of someedible andwound healing plants inOmanrdquo FoodChemistry vol101 no 2 pp 465ndash470 2007

[199] L-Q Jiang and H Takamura ldquoRadical-scavenging compoundsin olive fruits and their changes during table olive preparationrdquoAppliedMechanics andMaterials vol 295-298 pp 118ndash122 2013

[200] J E Hayes P Allen N Brunton M N OrsquoGrady and J P KerryldquoPhenolic composition and in vitro antioxidant capacity of fourcommercial phytochemical products olive leaf extract (Oleaeuropaea L) lutein sesamol and ellagic acidrdquo Food Chemistryvol 126 no 3 pp 948ndash955 2011


[201] H Jemai M Bouaziz and S Sayadi ldquoPhenolic compositionsugar contents and antioxidant activity of tunisian sweet olivecuitivar with regard to fruit ripeningrdquo Journal of Agriculturaland Food Chemistry vol 57 no 7 pp 2961ndash2968 2009

[202] S Silva L Gomes F Leitao A V Coelho and L V BoasldquoPhenolic compounds and antioxidant activity ofOlea europaeaL fruits and leavesrdquo Food Science and Technology Internationalvol 12 no 5 pp 385ndash395 2006

[203] O-H Lee B-Y Lee Y-C Kim K Shetty and Y-C KimldquoRadical scavenging-linked antioxidant activity of ethanolicextracts of diverse types of extra virgin olive oilsrdquo Journal ofFood Science vol 73 no 7 pp C519ndashC525 2008

[204] N Ben Othman D Roblain P Thonart and M HamdildquoTunisian table olive phenolic compounds and their antioxidantcapacityrdquo Journal of Food Science vol 73 no 4 pp C235ndashC2402008

[205] E Conde C Cara A Moure E Ruiz E Castro and HDomınguez ldquoAntioxidant activity of the phenolic compoundsreleased by hydrothermal treatments of olive tree pruningrdquoFood Chemistry vol 114 no 3 pp 806ndash812 2009

[206] I C F R Ferreira L Barros M E Soares M L Bastos and JA Pereira ldquoAntioxidant activity and phenolic contents of Oleaeuropaea L leaves sprayed with different copper formulationsrdquoFood Chemistry vol 103 no 1 pp 188ndash195 2007

[207] F Paiva-Martins J Fernandes S Rocha et al ldquoEffects of oliveoil polyphenols on erythrocyte oxidative damagerdquo MolecularNutrition amp Food Research vol 53 no 5 pp 609ndash616 2009

[208] L Abaza N ben Youssef H Manai F M Haddada KMethenni and M Zarrouk ldquoChetoui olive leaf extracts influ-ence of the solvent type on phenolics and antioxidant activitiesrdquoGrasas y Aceites vol 62 no 1 pp 96ndash104 2011

[209] H Turkez and B Togar ldquoOlive (Olea europaea L) leaf extractcounteracts genotoxicity and oxidative stress of permethrin inhuman lymphocytesrdquo Journal of Toxicological Sciences vol 36no 5 pp 531ndash537 2011

[210] I Muzzalupo F Stefanizzi E Perri and A A ChiappettaldquoTranscript levels of CHL 119901 gene antioxidants and chlorophyllscontents in olive (Olea europaea l) pericarps a comparativestudy on eleven olive cultivars harvested in two ripening stagesrdquoPlant Foods for Human Nutrition vol 66 no 1 pp 1ndash10 2011

[211] M Nadour P Michaud and F Moulti-Mati ldquoAntioxidantactivities of polyphenols extracted fromolive (Olea europaea) ofChamlal varietyrdquo Applied Biochemistry and Biotechnology vol167 no 6 pp 1802ndash1810 2012

[212] A Petridis I Therios and G Samouris ldquoGenotypic variationof total phenol and Oleuropein concentration and antioxi-dant activity of 11 Greek olive cultivars (Olea europaea L)rdquoHortScience vol 47 no 3 pp 339ndash342 2012

[213] R Malheiro N Rodrigues G Manzke A Bento J A Pereiraand S Casal ldquoThe use of olive leaves and tea extracts as effect-ive antioxidants against the oxidation of soybean oil undermicrowave heatingrdquo Industrial Crops and Products vol 44 pp37ndash43 2013

[214] M Machado C Felizardo A A Fernandes-Silva F M Nunesand A Barros ldquoPolyphenolic compounds antioxidant activityand l-phenylalanine ammonia-lyase activity during ripening ofolive cv lsquoCobrancosarsquo under different irrigation regimesrdquo FoodResearch International vol 51 no 1 pp 412ndash421 2013

[215] E Botsoglou A Govaris A Pexara I Ambrosiadis and DFletouris ldquoEffect of dietary olive leaves (Olea europaea L) onlipid and protein oxidation of refrigerated stored n-3-enriched

porkrdquo International Journal of Food Science amp Technology vol49 no 1 pp 42ndash50 2014

[216] G I Togna A R Togna M Franconi C Marra and MGuiso ldquoOlive oil isochromans inhibit human platelet reactivityrdquoJournal of Nutrition vol 133 no 8 pp 2532ndash2536 2003

[217] K AHomer FManji andD Beighton ldquoInhibition of peptidaseand glycosidase activities of Porphyromonas gingivalis Bac-teroides intermedius and Treponema denticola by plant extractsrdquoJournal of Clinical Periodontology vol 19 no 5 pp 305ndash3101992

[218] I Kubo and I Kinst-Hori ldquoTyrosinase inhibitory activity of theolive oil flavor compoundsrdquo Journal of Agricultural and FoodChemistry vol 47 no 11 pp 4574ndash4578 1999

[219] L I Somova F O Shode and M Mipando ldquoCardiotonic andantidysrhythmic effects of oleanolic and ursolic acids methylmaslinate and uvaolrdquo Phytomedicine vol 11 no 2-3 pp 121ndash1292004

[220] E Susalit N Agus I Effendi et al ldquoOlive (Olea europaea) leafextract effective in patients with stage-1 hypertension compar-ison with Captoprilrdquo Phytomedicine vol 18 no 4 pp 251ndash2582011

[221] C Circosta F Occhiuto A Gregorio S Toigo and A dePasquale ldquoThe cardiovascular activity of the shoots and leavesof Olea europaea L and oleuropeinrdquo Plantes Medicinales etPhytotherapie vol 24 no 4 pp 264ndash277 1990

[222] E Luibl ldquoLeaves of the olive tree in hypertensionrdquoMedizinischeMonatsschrift fur Pharmazeuten vol 12 pp 181ndash182 1958

[223] R Kosak and P Stern ldquoExamination of the hypotensive activityof folium olivaerdquo Acta Pharmaceutica Jugoslavia vol 6 pp 121ndash132 1956

[224] L I Somova F O Shode P Ramnanan and A Nadar ldquoAnti-hypertensive antiatherosclerotic and antioxidant activity oftriterpenoids isolated from Olea europaea subspecies africanaleavesrdquo Journal of Ethnopharmacology vol 84 no 2-3 pp 299ndash305 2003

[225] S Cherif N RahalMHaouala et al ldquoA clinical trial of a titratedOlea extract in the treatment of essential arterial hypertensionrdquoJournal de Pharmacie de Belgique vol 51 no 2 pp 69ndash71 1996

[226] M T Khayyal M A El-Ghazaly D M Abdallah N N NassarS N Okpanyi and M-H Kreuter ldquoBlood pressure loweringeffect of an olive leaf extract (Olea europaea) in L-NAMEinduced hypertension in ratsrdquo Arzneimittel-Forschung vol 52no 11 pp 797ndash802 2002

[227] T Perrinjaquet-Moccetti A Busjahn C Schmidlin ASchmidt B Bradl and C Aydogan ldquoFood supplementationwith an olive (Olea europaea L) leaf extract reduces blood pres-sure in borderline hypertensive monozygotic twinsrdquo Phyto-therapy Research vol 22 no 9 pp 1239ndash1242 2008

[228] A Scheffler H W Rauwald B Kampa U Mann F W Mohrand S Dhein ldquoOlea europaea leaf extract exerts L-type Ca2+channel antagonistic effectsrdquo Journal of Ethnopharmacologyvol 120 no 2 pp 233ndash240 2008

[229] G K Beauchamp R S J Keast D Morel et al ldquoIbuprofen-likeactivity in extra-virgin olive oilrdquo Nature vol 437 no 7055 pp45ndash46 2005

[230] S Esmaeili-Mahani M Rezaeezadeh-Roukerd K Esmaeilpouret al ldquoOlive (Olea europaea L) leaf extract elicits antinoci-ceptive activity potentiates morphine analgesia and suppressesmorphine hyperalgesia in ratsrdquo Journal of Ethnopharmacologyvol 132 no 1 pp 200ndash205 2010


[231] A Eidi S Moghadam-Kia J Z Moghadam M Eidi and SRezazadeh ldquoAntinociceptive and anti-inflammatory effects ofolive oil (Olea europeaeL) inmicerdquoPharmaceutical Biology vol50 no 3 pp 332ndash337 2012

[232] F R Nieto E J Cobos J M Entrena A Parra A Garcıa-Granados and J M Baeyens ldquoAntiallodynic and analgesiceffects of maslinic acid a pentacyclic triterpenoid from Oleaeuropaeardquo Journal of Natural Products vol 76 no 4 pp 737ndash740 2013

[233] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[234] S Sahranavard M Kamalinejad and M Faizi ldquoEvaluation ofanti-inflammatory and anti-nociceptive effects of defatted fruitextract of Olea europaeardquo Iranian Journal of PharmaceuticalResearch vol 13 supplement pp 119ndash123 2014

[235] D Dekanski S Janicijevic-Hudomal V Tadic G Markovic IArsic and D M Mitrovic ldquoPhytochemical analysis and gas-troprotective activity of an olive leaf extractrdquo Journal of theSerbian Chemical Society vol 74 no 4 pp 367ndash377 2009

[236] I Arsic A Zugic D R Antic et al ldquoHypericum perfora-tum L HypericaceaeGuttiferae sunflower olive and palm oilextracts attenuate cold restraint stressmdashinduced gastric lesionsrdquoMolecules vol 15 no 10 pp 6688ndash6698 2010

[237] B Fehri J-M Aiache S Mrad S Korbi and J-L LamaisonldquoOlea europaea L stimulant anti-ulcer and anti-inflammatoryeffectsrdquo Bollettino Chimico Farmaceutico vol 135 no 1 pp 42ndash49 1996

[238] H Kang and S Koppula ldquoOlea europaea linn Fruit pulp extractprotects against carbon tetrachloride-induced hepatic damagein micerdquo Indian Journal of Pharmaceutical Sciences vol 76 no4 pp 274ndash280 2014

[239] M Iriti S Vitalini G Fico and F Faoro ldquoNeuroprotectiveherbs and foods from different traditional medicines and dietsrdquoMolecules vol 15 no 5 pp 3517ndash3555 2010

[240] A Trichopoulou P Lagiou H Kuper and D TrichopoulosldquoCancer and Mediterranean dietary traditionsrdquo Cancer Epi-demiology Biomarkers and Prevention vol 9 no 9 pp 869ndash8732000

[241] C Vecchia and C Bosetti ldquoDiet and cancer risk in Mediter-ranean countriesrdquo Hungarian Medical Journal vol 1 no 1 pp13ndash23 2007

[242] T Guan Y-S Qian M-H Huang et al ldquoNeuroprotection ofmaslinic acid a novel glycogen phosphorylase inhibitor in type2 diabetic ratsrdquo Chinese Journal of Natural Medicines vol 8 no4 pp 293ndash297 2010

[243] Y Qian T Guan X Tang et al ldquoAstrocytic glutamate trans-porter-dependent neuroprotection against glutamate toxicityan in vitro study of maslinic acidrdquo European Journal of Phar-macology vol 651 no 1ndash3 pp 59ndash65 2011

[244] Y Qian T Guan X Tang et al ldquoMaslinic acid a naturaltriterpenoid compound from Olea europaea protects corticalneurons against oxygen-glucose deprivation-induced injuryrdquoEuropean Journal of Pharmacology vol 670 no 1 pp 148ndash1532011

[245] A Kaeidi S Esmaeili-Mahani V Sheibani et al ldquoOlive (Oleaeuropaea L) leaf extract attenuates early diabetic neuropathicpain through prevention of high glucose-induced apoptosis invitro and in vivo studiesrdquo Journal of Ethnopharmacology vol136 no 1 pp 188ndash196 2011

[246] F Mohagheghi M R Bigdeli B Rasoulian P Hashemi andM R Pour ldquoThe neuroprotective effect of olive leaf extract

is related to improved blood-brain barrier permeability andbrain edema in rat with experimental focal cerebral ischemiardquoPhytomedicine vol 18 no 2-3 pp 170ndash175 2011

[247] A Daccache C Lion N Sibille et al ldquoOleuropein and deriva-tives from olives as Tau aggregation inhibitorsrdquoNeurochemistryInternational vol 58 no 6 pp 700ndash707 2011

[248] Z Rabiei M R Bigdeli B Rasoulian A Ghassempour andF Mirzajani ldquoThe neuroprotection effect of pretreatment witholive leaf extract on brain lipidomics in rat stroke modelrdquoPhytomedicine vol 19 no 10 pp 940ndash946 2012

[249] H Pasban-Aliabadi S Esmaeili-Mahani V Sheibani MAbbasnejad A Mehdizadeh and M M Yaghoobi ldquoInhibitionof 6-hydroxydopamine-induced PC12 cell apoptosis by olive(Olea europaea L) leaf extract is performed by its main com-ponent oleuropeinrdquo Rejuvenation Research vol 16 no 2 pp134ndash142 2013

[250] L Diomede S Rigacci M Romeo M Stefani andM SalmonaldquoOleuropein aglycone protects transgenic C elegans strainsexpressing A12057342 by reducing plaque load and motor deficitrdquoPLoS ONE vol 8 no 3 Article ID e58893 2013

[251] S Y Al Okbi Z Hassan MM El Mazar N Ammar L T AbouElkassem and H F El Bakry ldquoDiuretic activity of olive (Oleaeuropaea L)rdquo Planta Medica vol 77 no 12 p 1415 2011

[252] U Koca I Suntar E K Akkol D Yilmazer and M AlperldquoWound repair potential of Olea europaea L leaf extractsrevealed by in vivo experimental models and comparative eval-uation of the extractsrsquo antioxidant activityrdquo Journal of MedicinalFood vol 14 no 1-2 pp 140ndash146 2011

[253] M Gholami-Ahangaran M Bahmani and N Zia-JahromildquoComparative and evaluation of anti-leech (Limnatis Nilotica)effect of Olive (Olea Europaea L) with Levamisol and Tiaben-dazolerdquoAsian Pacific Journal of Tropical Disease vol 2 no 1 ppS101ndashS103 2012

[254] A Sato N Shinozaki and H Tamura ldquoSecoiridoid type ofantiallergic substances in olive wastematerials of three Japanesevarieties of Olea europaeardquo Journal of Agricultural and FoodChemistry vol 62 no 31 pp 7787ndash7795 2014

[255] Z Rabiei M R Bigdeli and B Rasoulian ldquoNeuroprotectionof dietary virgin olive oil on brain lipidomics during strokerdquoCurrent Neurovascular Research vol 10 no 3 pp 231ndash237 2013

[256] S A OmerM A ElobeidM H Elamin et al ldquoToxicity of oliveleaves (Olea europaea L) in Wistar albino ratsrdquo Asian Journalof Animal and Veterinary Advances vol 7 no 11 pp 1175ndash11822012

[257] M Sanchez-Gonzalez G Lozano-Mena M E Juan A Garcıa-Granados and JM Planas ldquoAssessment of the safety ofmaslinicacid a bioactive compound from Olea europaea Lrdquo MolecularNutrition and Food Research vol 57 no 2 pp 339ndash346 2013

[258] R D A Ribeiro M M R F de Melo F de Barros C Gomesand G Trolin ldquoAcute antihypertensive effect in conscious ratsproduced by some medicinal plants used in the state of SaoPaulordquo Journal of Ethnopharmacology vol 15 no 3 pp 261ndash2691986

[259] M El Amin P VirkMAbdel-Rahman and et al ldquoAnti-diabeticeffect ofMurraya koenigii (L) andOlea europaea (L) leaf extractson streptozotocin induced diabetic ratsrdquo Pakistan Journal ofPharmaceutical Sciences vol 26 no 2 pp 359ndash365 2013

[260] Y Z H-Y Hashim J Worthington P Allsopp et al ldquoVirginolive oil phenolics extract inhibit invasion of HT115 humancolon cancer cells in vitro and in vivordquo Food amp Function vol5 no 7 pp 1513ndash1519 2014


[261] J Yao J Wu X Yang J Yang Y Zhang and L Du ldquoOleuropeininduced apoptosis in HeLa cells via a mitochondrial apoptoticcascade associated with activation of the c-Jun NH

2-terminal

kinaserdquo Journal of Pharmacological Sciences vol 125 no 3 pp300ndash311 2014

[262] D Dekanski M Dacevic and S Ristic ldquoOlive (Olea europaeaL) leaf extract inhibits lipid peroxidation in experimentallyinduced gastric mucosal injuryrdquo Basic amp Clinical Pharmacologyamp Toxicology vol 105 p 143 2009

[263] J A Pereira A P G Pereira I C F R Ferreira et al ldquoTableolives from Portugal phenolic compounds antioxidant poten-tial and antimicrobial activityrdquo Journal of Agricultural and FoodChemistry vol 54 no 22 pp 8425ndash8431 2006

[264] B Fehri S Mrad J-M Aiache and J-L Lamaison ldquoEffects ofOlea europaea L extract on the rat isolated ileum and tracheardquoPhytotherapy Research vol 9 no 6 pp 435ndash439 1995


Table 1 Common names of Olea europaea

S no Region Name

1 Spain Aceituna Olivera Olivo Oliondo OastreOliba

2 Lithuania Alyvos3 Portugal Azeitona Oliveira4 Romania Culoare masline Maslin Masliniu Oliva5 Albania Dege e ullirit Ngjyre ulliri Ulli6 Greece Elia7 Estonia Euroopa olipuu Olipuus8 Sweden Oliv Olivgront9 Slovakia Oliva europska10 Czech Republic Oliva Olivove drevo11 Latvia Olivas12 Denmark Oliven13 Germany Olivenbaum Olbaum14 Netherlands Olijf15 Israel Eylbert Masline Zayit16 India Jaitun Julipe Saidun17 Armenia Jitabdoogh Jiteni18 Bulgaria Maslina19 Croatia Maslinov20 South Africa Mohlware21 Hungary Olajbogyo Olajfa Oliva22 England Olewydden Olive23 Iceland Olifa24 Finland Oliivi Oljypuu25 Arab World Zaitoon26 France Oulivie Olive27 Switzerland Uliva28 Pakistan Zaitun29 Tanzania Zeituni30 Georgia Zetis

three countries are producing 60 of the worldrsquos total oliveproduction Outside these United States and Argentina arethe major producers of olive [16 17]

The therapeutic utilities of O europaea have been indi-cated in traditional medicine It has been known to reduceblood sugar cholesterol and uric acid It has also been usedto treat diabetes hypertension inflammation diarrhea res-piratory and urinary tract infections stomach and intestinaldiseases asthma hemorrhoids rheumatism laxative mouthcleanser and as a vasodilator Many phenolic compoundsespecially secoiridoids and iridoids [18] and their phar-macological activities have been the focus of attraction forscientists in the last decade [13 19] Oleuropein a majorconstituent of O europaea has got much attention and alot of work has been done on its pharmacological properties[20 21] Olive has widely been explored as a functional food[22 23] with various biophenols [24 25] and other bioactiveconstituents [26] Volatile constituents from olive oil and

their applications in flavor development have also been ahot area of the current research [27] A few reviews havebeen done on the phytochemistry of olive and olive oil inthe last decade [13 18 27 28] but the title plant is underimmense investigation by scientists all around the world[28 29] Continuous research is in progress to validate itstraditional medicinal uses which is described in detail in thepresent review

11 Botanical Description The olive tree (Figure 1(a)) is shortand thick generally from trees or shrubs to 10m in height Itstrunk possesses a large diameter typically bent and twisted Ithasmany reedy branches with opposite branchletsThe leavesare shortly stalked lanceolate sometimes ovate narrowoblong coriaceous leathery glabrous attenuate apex cute toacuminate margin entire pale green above with few scalesand silvery-whitish below in color petiole 5mm and 4ndash10 cmin length and 1ndash3 cm wide with 5ndash11 primary veins on eachside of the midrib and raised adaxially (Figure 1(b)) [30]The flowers are numerous bisexual or functionally unisexualsmall subsessile creamy white and feathery bulled mostlyon the wood of previous year (Figure 1(c)) Calyx is truncatewith four little teeth and corolla short with four lobes and is1-2mm long The olive fruit is small of which an outer fleshypart or skin surrounds a shell of hardened kernel The fruit isovoid blackish-violet when ripe normally 1ndash25 cm long andsmall in wild plants than in orchard cultivates (Figure 1(d))[31] The bark is pale grey in color (Figure 1(e)) [11]

O europaea is a monoecious plant [32] having bothperfect and imperfect flowers [15] so it depends on the windin which self- or cross-pollination occurs Cultivated plantsare normally pollinated by neighboring cultivars or even thewild form that is O sylvestris [33] Genetically O europaeais a diploid (2119899 = 46) species [34]

12 Cultivation The olive tree is one of the oldest cultivatedtrees on the planet earth [35] The cultivation of olive startedin ancient times and it dates back more than 7000 yearsAccording to archaeological reports olives were cultivated forcommercial purposes in Crete in 3000 BC by the Minoancivilization The use of olive oil for body health can be foundin ancient Greek literature [36] Earliest olive oil productiondates back to some 6500 years ago off the Carmel coast southof Haifa Israel [37] Olive trees spread to the West fromthe Mediterranean area into Italy Portugal Spain Greeceand France [38] Spanish Conquistadors in 1560 carried thecuttings and seeds of O europaea to Peru From there olivetrees spread to Mexico The Franciscan padres then carriedolives and other fruits from San Blas Mexico into CaliforniaOlive oil production began in San Diego in the next decade[39] It has been assumed that the cultivars around theMediterranean originated fromwildMediterranean olive andthen spread all around it [40]

Even though olive is now being cultivated in differentparts of the world the Mediterranean region is still servingas the major olive and its oil production area accounting forabout 98 of the worldrsquos olive cultivation [41] Nowadaysthere are more than 2000 cultivars in the Mediterranean


(a)

(b)

(c)

(d)

(e)



2 Phytochemistry








OR

OO

H

HOHOOH

H

R

O

O

O

H

O

O

OO

O O

H

R

O

HO

O

O O

O

O

O

ORH

OO

Glucosyl

Rhamnosyl

Caffeoyl

p-Coumaroyl

H

H Hydroxytyrosol

H

H

O

O

OR1

OR1

R2

OR2

OR1

COOR3

COOR3

COCH3

COOR3

COOCH3

COOCH3

CH 3

COOCH3

COOCH3

O

OH

OH

R2

R1 R2 R3

R1 R2 R3

R1 R2 R3

Glucosyl

Glucosyl

Glucosyl

Glucosyl

OH

OHOH

OH

H

H

H

H

H

H H

H

OHOH

OH

OH

HO

HO

HO

HO

HOHO

HO

OHHOHO

H

HH H

H

H

HH

HH

H

H H

H H

H

H

H

CH3

CH3

CH3

CH3

OCH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3Oleuropein (1)

Ligstroside (2)



Methyl acetal (6)

Methyl ether (7)






Oleuricine A (10)


HCH3




oleoside (17)


oleoside (18)


Comselogoside (20)

Oleuricine B (21)

Oleuroside (22)

Secologanin (23)

Secologanoside (24)


Nuzhenide (25) H


R2

R1

R1 R2




Figure 2 Continued


H H

O

O

O

OO

OHC

H

O

O

OH

OO

COOH

OO

O

O

H

H

H

O

O

O OO

R

O

O

O

OO

R O

O

O

O

H

O

H

O

O

OO

O

O

O

OO

O

O

H

O

O

OR

O

O

O

H

R

H

HO

O

O

O

O

O

O

OO

30

OHH

Ac

AcGlc

Glc

Glc

Glc

Ac

Ac

Hydroxytyrosol

H

H

H

HH

HH

CH3

OH

OH

OHOH

HO

HO

HOHO

HO

OHOH

OHOH OH

OH

OH

OHOH

OH

OHOH

OH

HO

HOHO

HOHO

HO

HOHO

HO

HOHO

HO

HO

HO

HO

HO

HOHOHO

HO

HO

HO

HO

R2R1

COOCH3

COOCH3 COOCH3

COOCH3

CH3

COOCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

CH3

H3C(H2C)7H3COOC

HOH2C

(H2 )7C

H3CO

OR2

OR1



Halleridone (38)

Cornoside (37)

R1 R2 R3

HHH

H

HH

H

OH

OH

OH

H

H

H

HHH

CH3

CH3

CH3



4998400998400-O-methyl ether (48)


34-DHPEA-DETA (31)




R1 R2

R1 R2

OH

OHOH

OHCH3


COOCH3


R3O

H3C

Figure 2 Continued


O

O

O

O

O

O O

H

O

O

O O O

O

H

HHHHHHHHHHHH

HHH

OO

O

HO

O

O






HH H

H H

H

Glucosyl

Glucosyl

OH Rhamnosyl H H

HHH

H


Glucosyl


Rhamnosyl


HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

HOHOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

OCH3

OCH3

COCH3

COCH3

OCH3

OCH3

OCH3

H3CO

H3CO

H3CO


Taxifolin (75)

OR6

OR1

OR2

Verucosin (58)

R1 R1

R1 R2

R1

R1 R2 R3 R4

R2

R1 R2

R1

R1

R1

R2

R7

R7R6

R5

R5

R4

R4

R3

R3

R2 R2

CH3

CH3

HHHHHHHHHHHHHHH

CH3


OR4

OR2

OR3


CH3

CH3



apiofuranosyl






OR2

Figure 2 Continued


O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5


1-oleyltyrosol (99)

Verbascoside (100)



Obtusifoliol (115)

Gramisterol (116)



OCH3



R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH


Uvaol (102)

Ursolic acid (103)




Cycloartenol (113)


OCH3


Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






(a)

(b)

(c)

(d)

(e)



2 Phytochemistry








OR

OO

H

HOHOOH

H

R

O

O

O

H

O

O

OO

O O

H

R

O

HO

O

O O

O

O

O

ORH

OO

Glucosyl

Rhamnosyl

Caffeoyl

p-Coumaroyl

H

H Hydroxytyrosol

H

H

O

O

OR1

OR1

R2

OR2

OR1

COOR3

COOR3

COCH3

COOR3

COOCH3

COOCH3

CH 3

COOCH3

COOCH3

O

OH

OH

R2

R1 R2 R3

R1 R2 R3

R1 R2 R3

Glucosyl

Glucosyl

Glucosyl

Glucosyl

OH

OHOH

OH

H

H

H

H

H

H H

H

OHOH

OH

OH

HO

HO

HO

HO

HOHO

HO

OHHOHO

H

HH H

H

H

HH

HH

H

H H

H H

H

H

H

CH3

CH3

CH3

CH3

OCH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3Oleuropein (1)

Ligstroside (2)



Methyl acetal (6)

Methyl ether (7)






Oleuricine A (10)


HCH3




oleoside (17)


oleoside (18)


Comselogoside (20)

Oleuricine B (21)

Oleuroside (22)

Secologanin (23)

Secologanoside (24)


Nuzhenide (25) H


R2

R1

R1 R2




Figure 2 Continued


H H

O

O

O

OO

OHC

H

O

O

OH

OO

COOH

OO

O

O

H

H

H

O

O

O OO

R

O

O

O

OO

R O

O

O

O

H

O

H

O

O

OO

O

O

O

OO

O

O

H

O

O

OR

O

O

O

H

R

H

HO

O

O

O

O

O

O

OO

30

OHH

Ac

AcGlc

Glc

Glc

Glc

Ac

Ac

Hydroxytyrosol

H

H

H

HH

HH

CH3

OH

OH

OHOH

HO

HO

HOHO

HO

OHOH

OHOH OH

OH

OH

OHOH

OH

OHOH

OH

HO

HOHO

HOHO

HO

HOHO

HO

HOHO

HO

HO

HO

HO

HO

HOHOHO

HO

HO

HO

HO

R2R1

COOCH3

COOCH3 COOCH3

COOCH3

CH3

COOCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

CH3

H3C(H2C)7H3COOC

HOH2C

(H2 )7C

H3CO

OR2

OR1



Halleridone (38)

Cornoside (37)

R1 R2 R3

HHH

H

HH

H

OH

OH

OH

H

H

H

HHH

CH3

CH3

CH3



4998400998400-O-methyl ether (48)


34-DHPEA-DETA (31)




R1 R2

R1 R2

OH

OHOH

OHCH3


COOCH3


R3O

H3C

Figure 2 Continued


O

O

O

O

O

O O

H

O

O

O O O

O

H

HHHHHHHHHHHH

HHH

OO

O

HO

O

O






HH H

H H

H

Glucosyl

Glucosyl

OH Rhamnosyl H H

HHH

H


Glucosyl


Rhamnosyl


HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

HOHOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

OCH3

OCH3

COCH3

COCH3

OCH3

OCH3

OCH3

H3CO

H3CO

H3CO


Taxifolin (75)

OR6

OR1

OR2

Verucosin (58)

R1 R1

R1 R2

R1

R1 R2 R3 R4

R2

R1 R2

R1

R1

R1

R2

R7

R7R6

R5

R5

R4

R4

R3

R3

R2 R2

CH3

CH3

HHHHHHHHHHHHHHH

CH3


OR4

OR2

OR3


CH3

CH3



apiofuranosyl






OR2

Figure 2 Continued


O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5


1-oleyltyrosol (99)

Verbascoside (100)



Obtusifoliol (115)

Gramisterol (116)



OCH3



R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH


Uvaol (102)

Ursolic acid (103)




Cycloartenol (113)


OCH3


Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






OR

OO

H

HOHOOH

H

R

O

O

O

H

O

O

OO

O O

H

R

O

HO

O

O O

O

O

O

ORH

OO

Glucosyl

Rhamnosyl

Caffeoyl

p-Coumaroyl

H

H Hydroxytyrosol

H

H

O

O

OR1

OR1

R2

OR2

OR1

COOR3

COOR3

COCH3

COOR3

COOCH3

COOCH3

CH 3

COOCH3

COOCH3

O

OH

OH

R2

R1 R2 R3

R1 R2 R3

R1 R2 R3

Glucosyl

Glucosyl

Glucosyl

Glucosyl

OH

OHOH

OH

H

H

H

H

H

H H

H

OHOH

OH

OH

HO

HO

HO

HO

HOHO

HO

OHHOHO

H

HH H

H

H

HH

HH

H

H H

H H

H

H

H

CH3

CH3

CH3

CH3

OCH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3Oleuropein (1)

Ligstroside (2)



Methyl acetal (6)

Methyl ether (7)






Oleuricine A (10)


HCH3




oleoside (17)


oleoside (18)


Comselogoside (20)

Oleuricine B (21)

Oleuroside (22)

Secologanin (23)

Secologanoside (24)


Nuzhenide (25) H


R2

R1

R1 R2




Figure 2 Continued


H H

O

O

O

OO

OHC

H

O

O

OH

OO

COOH

OO

O

O

H

H

H

O

O

O OO

R

O

O

O

OO

R O

O

O

O

H

O

H

O

O

OO

O

O

O

OO

O

O

H

O

O

OR

O

O

O

H

R

H

HO

O

O

O

O

O

O

OO

30

OHH

Ac

AcGlc

Glc

Glc

Glc

Ac

Ac

Hydroxytyrosol

H

H

H

HH

HH

CH3

OH

OH

OHOH

HO

HO

HOHO

HO

OHOH

OHOH OH

OH

OH

OHOH

OH

OHOH

OH

HO

HOHO

HOHO

HO

HOHO

HO

HOHO

HO

HO

HO

HO

HO

HOHOHO

HO

HO

HO

HO

R2R1

COOCH3

COOCH3 COOCH3

COOCH3

CH3

COOCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

CH3

H3C(H2C)7H3COOC

HOH2C

(H2 )7C

H3CO

OR2

OR1



Halleridone (38)

Cornoside (37)

R1 R2 R3

HHH

H

HH

H

OH

OH

OH

H

H

H

HHH

CH3

CH3

CH3



4998400998400-O-methyl ether (48)


34-DHPEA-DETA (31)




R1 R2

R1 R2

OH

OHOH

OHCH3


COOCH3


R3O

H3C

Figure 2 Continued


O

O

O

O

O

O O

H

O

O

O O O

O

H

HHHHHHHHHHHH

HHH

OO

O

HO

O

O






HH H

H H

H

Glucosyl

Glucosyl

OH Rhamnosyl H H

HHH

H


Glucosyl


Rhamnosyl


HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

HOHOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

OCH3

OCH3

COCH3

COCH3

OCH3

OCH3

OCH3

H3CO

H3CO

H3CO


Taxifolin (75)

OR6

OR1

OR2

Verucosin (58)

R1 R1

R1 R2

R1

R1 R2 R3 R4

R2

R1 R2

R1

R1

R1

R2

R7

R7R6

R5

R5

R4

R4

R3

R3

R2 R2

CH3

CH3

HHHHHHHHHHHHHHH

CH3


OR4

OR2

OR3


CH3

CH3



apiofuranosyl






OR2

Figure 2 Continued


O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5


1-oleyltyrosol (99)

Verbascoside (100)



Obtusifoliol (115)

Gramisterol (116)



OCH3



R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH


Uvaol (102)

Ursolic acid (103)




Cycloartenol (113)


OCH3


Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






H H

O

O

O

OO

OHC

H

O

O

OH

OO

COOH

OO

O

O

H

H

H

O

O

O OO

R

O

O

O

OO

R O

O

O

O

H

O

H

O

O

OO

O

O

O

OO

O

O

H

O

O

OR

O

O

O

H

R

H

HO

O

O

O

O

O

O

OO

30

OHH

Ac

AcGlc

Glc

Glc

Glc

Ac

Ac

Hydroxytyrosol

H

H

H

HH

HH

CH3

OH

OH

OHOH

HO

HO

HOHO

HO

OHOH

OHOH OH

OH

OH

OHOH

OH

OHOH

OH

HO

HOHO

HOHO

HO

HOHO

HO

HOHO

HO

HO

HO

HO

HO

HOHOHO

HO

HO

HO

HO

R2R1

COOCH3

COOCH3 COOCH3

COOCH3

CH3

COOCH3

OCH3

OCH3

OCH3

OCH3

OCH3

OCH3

CH3

H3C(H2C)7H3COOC

HOH2C

(H2 )7C

H3CO

OR2

OR1



Halleridone (38)

Cornoside (37)

R1 R2 R3

HHH

H

HH

H

OH

OH

OH

H

H

H

HHH

CH3

CH3

CH3



4998400998400-O-methyl ether (48)


34-DHPEA-DETA (31)




R1 R2

R1 R2

OH

OHOH

OHCH3


COOCH3


R3O

H3C

Figure 2 Continued


O

O

O

O

O

O O

H

O

O

O O O

O

H

HHHHHHHHHHHH

HHH

OO

O

HO

O

O






HH H

H H

H

Glucosyl

Glucosyl

OH Rhamnosyl H H

HHH

H


Glucosyl


Rhamnosyl


HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

HOHOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

OCH3

OCH3

COCH3

COCH3

OCH3

OCH3

OCH3

H3CO

H3CO

H3CO


Taxifolin (75)

OR6

OR1

OR2

Verucosin (58)

R1 R1

R1 R2

R1

R1 R2 R3 R4

R2

R1 R2

R1

R1

R1

R2

R7

R7R6

R5

R5

R4

R4

R3

R3

R2 R2

CH3

CH3

HHHHHHHHHHHHHHH

CH3


OR4

OR2

OR3


CH3

CH3



apiofuranosyl






OR2

Figure 2 Continued


O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5


1-oleyltyrosol (99)

Verbascoside (100)



Obtusifoliol (115)

Gramisterol (116)



OCH3



R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH


Uvaol (102)

Ursolic acid (103)




Cycloartenol (113)


OCH3


Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






O

O

O

O

O

O O

H

O

O

O O O

O

H

HHHHHHHHHHHH

HHH

OO

O

HO

O

O






HH H

H H

H

Glucosyl

Glucosyl

OH Rhamnosyl H H

HHH

H


Glucosyl


Rhamnosyl


HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

HOHOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

OCH3

OCH3

COCH3

COCH3

OCH3

OCH3

OCH3

H3CO

H3CO

H3CO


Taxifolin (75)

OR6

OR1

OR2

Verucosin (58)

R1 R1

R1 R2

R1

R1 R2 R3 R4

R2

R1 R2

R1

R1

R1

R2

R7

R7R6

R5

R5

R4

R4

R3

R3

R2 R2

CH3

CH3

HHHHHHHHHHHHHHH

CH3


OR4

OR2

OR3


CH3

CH3



apiofuranosyl






OR2

Figure 2 Continued


O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5


1-oleyltyrosol (99)

Verbascoside (100)



Obtusifoliol (115)

Gramisterol (116)



OCH3



R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH


Uvaol (102)

Ursolic acid (103)




Cycloartenol (113)


OCH3


Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






O

O

O

O

O

OO

O O

O

O

H

H

H

H

H

H

COOH

H

H

H

H

H

COOHR

COOHR

R O

HH

HH

HH

H

H

H

H

H

COOH H

COOH OH

COOH H

COOH H

H

COOH OH

OH OHH OHH H

HOHH

OH

OH

OH

OH

OH

OH

OH

HO HO

HOHO

HO

HO

HO

HO

OH

OH

HO

HO

HO

HO

HO

HO

HO

HO

HO

HOHO

HO

OCH3

CH3

R4

R3R2

R1

R5

(CH2)5(CH2)5


1-oleyltyrosol (99)

Verbascoside (100)



Obtusifoliol (115)

Gramisterol (116)



OCH3



R1 R5R4R3R2

R1 R2

CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH2OH


Uvaol (102)

Ursolic acid (103)




Cycloartenol (113)


OCH3


Figure 2 Continued


O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






O

C

HC

C

OO

COOH

R

R

COOH

H

R

R

R

R

O

OO

OO

O

O

O

O

O

R

O

O

HH

R

O

O

R

O

O

H

R

HOH

CHO

CHOCOOH

OH

HOH

H

HOHO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

HO

HOHO

HO HO

HO

HOHO

HO

HOHO

H3CO

OCH3

CH2CO2CH3

CH2OH

CH2CO2CH3









CH3
























4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






















4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal











4 Pharmacology























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal

























2O2-










5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal











5Erythrodiol uvaol





(BBCE)

Good FGF-2 [154]


























radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal



















radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal










radicals[196]



assayDMSO [175]




























phenolic content




Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






Table 5 Continued







[263]







acid[192]














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal














2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal







2O2)


















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal

















baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal









baclofen [232]















in mice [238]








50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal







50


5 Toxicology


6 Conclusion





Acknowledgment


References





























































































































































2O2


























































































































2-terminal






























































































































































2O2


























































































































2-terminal






















































































































2O2


























































































































2-terminal




















































































2O2


























































































































2-terminal

















































2O2


























































































































2-terminal














2O2


























































































































2-terminal







































































































2-terminal







































































2-terminal







































2-terminal







2-terminal





Documents

Traditional Uses, Phytochemistry, and Pharmacology of Olea europaea (Olive)