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Author's personal copy

Journal of Ethnopharmacology 131 (2010) 229–241

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Journal of Ethnopharmacology

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Review

Dittany of Crete: A botanical and ethnopharmacological review

Christos C. Lioliosa,b, Konstantia Graikoua, Eleni Skaltsaa, Ioanna Chinoua,∗

a School of Pharmacy, Department of Pharmacognosy-Chemistry of Natural Products, University of Athens, 157 71, Greeceb Department of Pharmacy, Laboratory of Pharmacokinetics, University of Patras, Rio 26504, Greece

a r t i c l e i n f o

Article history:Received 30 October 2009Received in revised form 7 June 2010Accepted 8 June 2010Available online 13 July 2010

Keywords:Origanum dictamnusHistory and traditional usesChemical componentPharmacological activity

a b s t r a c t

Origanum dictamnus (Lamiaceae family), an endemic plant of the Greek island of Crete, is widely usedas a traditional medicine since antiquity, all over Europe. The aim of the present review is to presentcomprehensive information of the plant’s botanical taxonomy and morphology, as well as of the chem-ical constituents, biological and pharmacological research on O. dictamnus, which will be presented andcritically evaluated. The paper also highlights particularly interesting aspects and common medicinaluses not previously described in the specific ethnobotanical literature. An increasing number of chemicaland pharmacological studies have been reported recently, some of which strongly support its traditionalmedicinal uses against various illnesses such as sore throat, cough and gastric ulcer. A variety of com-pounds, including flavonoids, lipids and terpenoids (mainly carvacrol and thymol) have been identifiedfrom the plant. Current studies have showed that the extracts, the essential oil, as well as their active prin-ciples possess several pharmacological properties, like antimicrobial, antioxidant and anti-ulcer ones. Therecent scientific data and the rich historical evidence of its medicinal uses could support further researchas well as its use as a safe herbal medicinal product.

© 2010 Elsevier Ireland Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2302. Distribution and taxonomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2303. Morphology and anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2304. Mythology and history . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2315. Ancient and common names and their origin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2326. Ethnobotany, collection and cultivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2337. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234

7.1. Chemical analysis of plant extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2347.2. Chemical analysis of essential oil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234

8. Biological activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2358.1. Biological activities of O. dictamnus extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

8.1.1. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2358.1.2. Antioxidative activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2358.1.3. Cytotoxic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237

8.2. Biological activities of O. dictamnus essential oil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2388.2.1. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2388.2.2. Insecticidal effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238

8.3. Therapeutical uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2388.3.1. Known traditional uses (not supported by in vivo experimental data) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2388.3.2. Safety and pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2398.3.3. Mutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239

9. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240

Abbreviations: AP, aerial parts; B, bracts; L, leaves; F, flowers; NS, not specified; HS, headspace analysis; Ex, CH2Cl2 extract; C, cultivated; W, wild; HC, hydroponic cultivated;P, platyphylus; S, stenophylus; MIC, minimal inhibition concentration; ID, inhibition dose; T/C, relative increase of animal survival against a control group; ca., circa.

∗ Corresponding author. Tel.: +30 210 7274595; fax: +30 210 7274115.E-mail address: [email protected] (I. Chinou).

0378-8741/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.jep.2010.06.005


230 C.C. Liolios et al. / Journal of Ethnopharmacology 131 (2010) 229–241

1. Introduction

Origanum dictamnus L. (Fig. 1) is a Greek endemic species ofthe island of Crete, where it grows wild, from sea level up tothe high mountains (Fernandes and Heywood, 1972; Ietswaart,1980). “dittany of Crete”, “dictamnos” or “dictamnon”, is a plantwell known since antiquity for its medicinal applications (woundtreatment, “panacea”), which were related to the ancient GreekGods and mythology (Berendes, 1902; Skrubis, 1979; Thanos, 1994;Baumann, 1996). Nowadays, dittany is still widely used, as aherbal tea plant, as a condiment and in distilleries abroad, holdinggreat commercial value for the local Greek economy (Skoula andKamenopoulos, 1997; Hanlidou et al., 2004). Because of its wideapplication as a traditional herbal medicinal product, it receivesgrowing attention from modern pharmacology. There are vari-ous examples in recent literature where plant decoctions and theessential oils of O. dictamnus are tested for pharmacological effects(Pellecuer et al., 1980; Gergis et al., 1990; Economou et al., 1991;Panizzi et al., 1993; Lagouri and Boskou, 1996; Sivropoulou et al.,1996; Lionis et al., 1998; Moller et al., 1999; Economakis et al.,1999; Daferera et al., 2000; Karanika et al., 2001; Economakis et al.,2002; Goun et al., 2002; Couladis et al., 2003; Daferera et al., 2003;Stamatis et al., 2003; Chinou et al., 2007; Kouri et al., 2007; Liolioset al., 2009). Additionally, since it is characterized by the U.S.A. CFR(2009) as a safe spice for consumption, it can be easily applied asa natural additive in food industry, with flavouring, antioxidant orpreservative role (Liolios et al., 2009).

The present paper is a brief review of all the historical, eth-nobotanical, phytochemical and preclinical works published ondittany, until today. It has also been attempted to evaluate particu-larly interesting applications of the plant, which to our knowledge

Fig. 1. Photo of wild dittany (Crete) (J. Silignakis).

have not been reported in any scientific review before, in order toprovide an original view of its ethnopharmacological importancein Greece and elsewhere.

2. Distribution and taxonomy

O. dictamnus L. (syn. = O. pseudodictamnus Sieber, Amaracus dic-tamnus (L.) Bentham) is a chasmophyte endemic of Crete. It is ashort green white lanate shrub, which stems up to 35 cm. Its stemsare ascending and rooting at the bases, yellow or purplish brown,lanate (hairs ca. 2 cm long, branched). Branches of the first orderabsent or present, in the upper half of the stems, up to 5 pair perstem, 1.5 cm long, not ramified. Leaves up to 15 pairs per stem,lower ones petiolate (petioles up to 15 cm long), roundish to oval orovate, tops obtuse or acute, 15 mm long, 15 mm wide, thin, whitish(green), both sides are lanate (hairs 2 mm long, branched), sessileglands inconspicuous, up to 600 per cm2; margins revolute; veinsraised at the underside. Spikes subglobose to cylindrical, 16 cmlong, 7 cm wide, nodding. Bracts 8 pairs per spike, roundish toovate, tops obtuse or acute 9 mm long, 7 mm wide, more or lesspurple, glabrous or sparcely ciliate. Flowers two per verticillaster,subsessile. Calyses 1-lipped for c.3/5, 5 mm long, throats sparcelypilose or not, for the rest glabrous; upper lips (sub)entire; lower lipsabsent or consisting of 2 very small (0.5 mm long) lobes. Corollastwo lipped 11 mm long, pink, more or less saccate, outside sparselypilosellous; upper lips divided into 2. 0.3 mm long lobes; lower lipsdivided into subequal, 1.5 mm long lobes. Staminal filaments up to12 and 14 mm long. Styles between the filaments protruding underthe upper lips, up to 18 mm long. Roots up to 1 cm in diameter(Ietswaart, 1980). It grows wild inside fissures of calcareous cliffs;usually it prefers shadowy places (Ietswaart, 1980; Turland, 1995)from 300 up to 1500 m above sea level (Ietswaart, 1980). It flowersfrom June to October (Ietswaart, 1980).

Dittany is widely distributed along Crete with more dense popu-lations on the Western part, while it is doubtfully reported presentin Southwest Asiatic Turkey (Ietswaart, 1980; Med-Checklist, 1986;Turland, 1995). Dittany looks a lot like the plant O. calcaratum Juss(syn. O. tournefortii Aiton, A. tournefortii Bentham), from which itdiffers in its lannate and thinner leaves, its less compact inflo-rescences and usually subglobose spikes (Ietswaart, 1980). Earlierbotanists, classified Amaracus (Gleditsch) Bentham as a differentgenus from Origanum and Majorana (Rechinger, 1943; Diapoulis,1949; Kavadas, 1956), while contemporary studies consider thatdittany belongs in the genus Origanum, sect. Amaracus (Gled-itsch) Bentham of Lamiaceae family (Fernandes and Heywood,1972; Ietswaart, 1980). According to recent studies by Ietswaart(1980), who monographed genus Origanum eight sections canbe recognised, which can be arranged in three informal groups.O dictamnus belongs in the third group, which contains plantswith unequally lobed calyces, and also have large membranousbracts (Paton, 1994). Section Amaracus (Gleditsch) Bentham, isconsidered to include ancient forms of genus Origanum, most ofwhich were created during Pliocene (Ietswaart, 1980, 1982). Allthe known hybrids of dittany are: Origanum hybridinum Miller(O. dictamnus × O. sipyleum), O. amanum × O. dictamnus, O. cal-caratum × O. dictamnus (Ietswaart, 1980; Skoula and Harborne,2002).

3. Morphology and anatomy

The leaf of O. dictamnus is nearly rounded, densely covered withbranched non-glandular hairs, which lend to it a velvety appear-ance. They are more numerous on the lower brighter leaf side. Theyconsist of many cells and they seem to have a protective role. Thebranching of non-glandular hairs, while it is frequent for O. dictam-


C.C. Liolios et al. / Journal of Ethnopharmacology 131 (2010) 229–241 231

nus, it rarely occurs in the other species of the genus such as O.vulgare, O. onites (Bosabalidis, 2002).

The leaf also bears glandular hairs, in lesser numbers than thenon-glandular hairs. Glandular hairs are divided in two categories:capitate and peltate glandular hairs. Capitate hairs consist of onehead, one basal cell and one to five stalk cells between them. Peltatehairs are bigger than capitates ones, short and voluminous. They arecomposed of a large basal cell, a flattened stalk cell and a multicel-lular head (the number of cells differ depending on the memberof the family, and is 8 cells for O. dictamnus. Both categories havesecretory role. Their head cell stores the precious essential oil ofthe plant (Bosabalidis and Tsekos, 1982). The transversal sectionof the leaf is typical for Lamiaceae family plants, different onlyat the length and width of the palisade parenchyma cells and thedensity of chloroplasts. The density of the glandular hairs of O. dic-tamnus is less than in the other plants of the Lamiaceae family.This is in agreement with the great density of non-glandular hairsand closely connected with the harsh environmental conditionsin the natural growing environment of the plant (Bosabalidis andTsekos, 1982; Bosabalidis and Papadopoulos, 1983; Bosabalidis,2002, 1990, 1987a,b; Vrachnakis, 2003).

4. Mythology and history

According to ancient mythology the plant was dedicated to theancient Cretan goddess Diktynna and thus was named dittany.The goddess or nymph Diktynna was in later times matched withArtemis (Diana) and became Artemis-Diktynna, famous as the god-dess of the forest, the hunt, the mountains, the springs and therivers. Greek Mythology tells us that Minos, the famous Cretan kingof the Minoan civilization, fell in love with her, chased her, and inorder to avoid him she fell into the sea, near the cape of Psakos(known today as Spatha), but she was saved by the fish-nets oflocal fishermen, so they gave her the name Diktynna from the Greekword “Dikti” (=net).

Moreover, both Artemis and dittany were believed to magi-cally cure arrow wounds. This relationship explains why Artemisis often represented with an O. dictamnus crown on her head(Skoula and Kamenopoulos, 1997). Excavations in Knossos palace(near Heraklion city, Crete), Zacros (east coast of Crete, south ofPalaikastro), and the Royal palace of Mycenae as well as in thepalace of Pylos (North East and South Peloponnese respectively),revealed seeds of different kinds of aromatic plants, like O. dic-tamnus, Artemisia absinthium (common wormwood), Salvia trilobaand others. This proves the existence of ancient laboratories, whichproduced essences and cosmetics using aromatic plants as rowmaterials. Especially between 1700 and 1450 BC, the so-called “nat-uralistic period”, the Minoan civilization for the first time in thehistory of mankind used plants for decorating pottery and murals.Some of the pictures are so realistic that the species of the plant canbe identified. Among the plants depicted we can recognise dittany(Diapoulis, 1980).

Besides, the plant relates to Roman goddess of hunting Artemis-Diana, so it was named “Artemidio”. For both cases the link betweengoddess Artemis and dittany was probably due to the fact that boththe plant and the goddess assisted childbirth. Before Zeus (Jupiter)arrived in the Aegean Sea, Cretan goddess “Ilithia” or “Elethia” wasdedicated to childbirth, but she was later on also connected toArtemis. Euripides (ca. 480–406 BC), one of the three great trage-dians in classical Athens, in his tragedy “Hippolytus” states thatgoddess Ilithia (Artemis-Diana) wears a crown made of a plant,which according to later scholars (Schwartz, 1891) could have beendittany (Scholia in Euripidem, Argumentum Hippolyti, 73.46).

Since ancient times, dittany was considered as “panacea”, whichmeans a drug against every illness. So it was thoroughly used

Fig. 2. The famous engraving of Dapper showing a wounded Kri-Kri (Cretangoat) eating O. dictamnus for healing (Amsterdam 1703). http://dittany-of-crete.com/history.aspx.

for stomach disorders, gastric ulcers, for the digestive system ingeneral, spleen problems, against rheumatism, to facilitate child-birth and against gynaecological disorders. The marvellous powerof this plant has been extolled by at least twenty-four writersfrom antiquity up to the fourth century. Homer (9th century BC)(Iliad, 11.843-847) reported that a bitter root was used as a cureagainst gastric ulcers and bleeding (Homer, 1920, 1924), which inlater times has been identified as dittany (Berendes, 1889, 1902).Hippocrates (5th–4th century BC) (De natura muliebri, 32.1; demulierium affectibus i–iii, 46.6; de exsectiones foetus, 4.11) thefather of medicine, used it on Cos island, against gall bladder ail-ments, tuberculosis and in poultices for wounds; it has also beenstated that it could induce abortion (Hippocrates, Med., et CorpusHippocraticum, 1853). The most interesting reference to the medic-inal power of O. dictamnus came from Aristotle (4th century BC)(Historia Animalium 9.7.1), who stated that when wild goats ofMount Ida (Crete) were struck by poisoned arrows, they ate aerialparts of O. dictamnus, which had the effect of causing the arrowsto leave their bodies and of healing their wounds (Aristotle, 1994,2000). Theophrastus (4th–3rd century BC) (Historia plantarum,9.16.1) repeated his master’s (Aristotle) previous statement butwith scepticism (Theophrastus, 2007). This story was retold evenuntil the seventeenth century, when it inspired the making of aquite famous engraving (Fig. 2). The engraving is found in the workof the Flemish travel-writer O. Dapper “Description exacte dei ilesde l’Archipelago” (Amsterdam, 1703), who repeated the previouslymentioned story (Baumann, 1996; Thanos, 1994; Skrubis, 1979;Berendes, 1902).

Latin writers Cicero (2nd–1st century BC) in his work “De NaturaDeorum” (2.126) (Cicero Tullius, 1917) and Virgil (1st centuryBC) in “Aeneid” (12.412) attributed many virtues to O. dictamnus(Virgilius, 1903). Specifically in the work of the famous poet Vir-gil, it can be seen Aphrodite, the ancient goddess of love, showingher lavish care for the Trojan hero Aeneas using the Cretan O. dic-tamnus to heal his wounds (Fig. 3) (Hunt, 2005). Dittany was also



Fig. 3. Pompeiian wall-painting quoting the Aeneid. The old physician Iapyx attend-ing the wounded Aeneas (vulnus XII.389), while Venus herself arrives, bringingwith her the healing Cretan herb dittany (Venus..dictamnum..carpit ab Ida..detulitXII.411–417. Museo Nazionale in Naples. From the Casa de Sirico, first century BCE(Hunt, 2005).

mentioned by the Latin writers Pliny (Gajus Plinius secundus, 1stcentury AD) in “Naturalis Historia” (8.44) (Plinius Secundus, 1685;Plinius Secundus, 1906) and Celsus (Aulus Cornelius Celsus, 1st cen-tury BC) in “De Medicina” (5.25.13), who suggested that we needfour sips of NH3 or water solution of the plant in order to havethe desired effects (Celsus, 1971). Later on, the Greeks Plutarch(1st–2nd century AD) (Plutarch, 1954) and Dioscorides (1st centuryAD) in his work “De Materia Medica” (Codex Vindobonenis) (Fig. 4)attributed to dittany similar properties with Aristotle (Wellmann,1958; Gunther, 1959; Dioscurides, 1970, 2010). Finally, Galen, thefamous Greek physician, who is considered to be the “father ofPharmacy” Galen (2nd century AD) in his works: “De compositionemedicamentorum” and “De antidotis”, attributed to dittany heal-ing, as well as anti-rheumatism and abortion properties (Galeni,1827).

During the middle ages, dittany was recorded in the code ofCarlomagnus (8th–9th century AD) about 795 AD “. . .diptamnum,sinape, satureiam, sisimbrium, mentam, mentastrum..” (chapter LXX.)(Fig. 5). Linnaeus (18th century AD) fully identified O. dictamnusbotanically much later in “Species Plantarum” (1753 AD) (Fig. 6)(Linnean Herbarium, 2003). Dittany was also widely used in monas-teries since the Middle Age, in the famous liqueurs Benedictine andTrappistine by the Benedictines and Trappistines monks, respec-tively. Even in our days, dittany is used in distilleries. Vermouth(Cinzano) for example is flavoured with this very aromatic plant(Baumann, 1996; Plimakis, 1997).

Ditanny has been referred very often in Greek literature andpoetry as a plant symbol of Crete and Greece (Nobel prize ownerElytis, 1972).

5. Ancient and common names and their origin

Various names have been attributed to dittany in the ancientworld (Table 1), among them the name dictamnos, which survives

Fig. 4. Dioscorides, “De Materia Medica” Codex Vindobonensis.

Fig. 5. The Code of Carlomagnus. Capitulare de villis vel curtis imperii de Charle-magne (Charlemagne, 795).



Table 1Botanical synonyms, vernacular and ancient names of dittany.

Scientific names Synonyms Ancient names

Origanum dictamnus Linnaeus Majorana dictamnus (Linnaeus) Kosteletzky Greeks: artemidio, baetion, dorkadion (dorcidium),ekvolion (elbunium), okytokos velotoko, veloulkos,velonoxo, (Wellmann, 1958, Gunther, 1959)

Family: Lamiaceae [Labiatae] Amaracus dictamnus (Linnaeus) Bentham, Romans: ustilago rustica (Gunther, 1959)Dictamnus creticus J. HillOriganum saxatile SalisburyAmaracus tomentosus Moench, Origanum pseudodictamnusSieberMajorana tomentosa StokesOriganum pseudodictamnus SieberOriganum dictamnifolium Saint-Lager

Selected vernacular names: Greece: diktamos, adichtamos, atitamos, diktami, erontas, levanochorto, malliarochorto, stathоri, stamatochorto, stomachohorto, stomatochorto,titamos, attitamos, simpsychi, gerontas, diapsychos, wild origanum, kefalochorto (Liolios et al., 2009; Argyropoulou et al., 2009; Henelt, 2001; Daferera et al., 2000; Skoulaand Kamenopoulos, 1997; Harvala et al., 1987; Skaltsa and Harvala, 1986; Skaltsa and Harvala, 1987; Skrubis, 1979; Schaden and Hesse, 1976).England: dittany of Crete or Candia, dictamnus, dictamna hops, winter sweet, dittany (Henelt, 2001; Paton, 1994).Germany: kretische diptam, diptamdosten, kretadiptam, dictamno, kreta-majoran, majoran, kreta (Fenaroli and Burdock, 2004; Henelt, 2001; Schaden and Hesse, 1976).Italy: origano de Creta, dittamo di Candia, dittamo Cretico (De Vincenzi et al., 2004; Henelt, 2001; Skrubis, 1979; Fenaroli and Burdock, 2004).France: dictame de Crete, dictame vrai, origan dictame (Fenaroli and Burdock, 2004; Henelt, 2001; Polunin, 1969; Fournier, 1947).Spain: dictamo cretico (Pharmacopoea Hispanica, 1826).

till our days, probably derived from “Dicti” + “thamnos” (Skrubis,1979). “Dicti” comes from the name of Cretan mountain “KnossiaDicti”, where Zeus (Jupiter) was raised up by the goat Amalthia,and it was dedicated to him and “thamnos” means shrub in Greek.Today, this mountain is called Yiucta and O. dictamnus is known togrow wild in great quantities. Another view on dittany’s name ori-gin states, that it derives from the ancient Cretan goddess or nymph“Dictynna” as it has been mentioned referred in Mythology and his-tory (Part 4) (Skoula and Kamenopoulos, 1997). Ancient names like“veloulko”, “velotoko” probably derive from the magical ability ofthe plant to heal arrow wounds (Gennadios, 1914) (“velos” = arrowin Greek); which O. dictamnus was strongly believed to possess.

Fig. 6. O. dictamnus identified by Linnaeus (1753 A.D.). Pictures from the prototypearchives of Linnaeus (Linnean Herbarium, 2003).

Nowadays, the plant is widely known across the world by vari-ous vernacular names (Table 1). Among those, the name “erontas”,attributed to dittany by the local people of Crete, presents greatinterest because it probably derives from “Erotas”, the ancientGreek god of love. Like the edelweiss (Leontopodium alpinum L.)O. dictamnus was offered to girls as an expression of love. Dittanygrows wild, high in the mountains, in places difficult to be reached,thus it was believed that someone had to be fully in love in order toclimb and gather the plant to be offered (Fragaki, 1969; Plimakis,1997).

Additionally, the name of the genus “Origanum”, accordingto some researchers has its roots in the Greek words “oros”(mountain) + “ganos” (from “ganimai-ganousthai”, which meansbecoming bright or being happy). This name probably originatesfrom and is closely associated with the high mountains the natu-ral growing environment of Origanum plants in the Mediterranean(Panou-Filotheou et al., 1997).

The name of dittany “stamatochorto”, which in Greek means“stopping herb” originates from the Greek words “stamato” (=tostop) and “horto” (=herb), and probably derives from the propertyof dittany to stop bleeding. Furthermore the name “stoma-chohorto”, literally meaning “herb for the stomach”, originatesfrom the words “stomach” and “horto” and refers to its healingproperty to cure stomach ache. Additionally, the word “stomato-horto” originates from the words “stoma” (=mouth) and “horto”and refers to the plant’s property to refresh the mouth (Plimakis,1997; Skoula and Kamenopoulos, 1997). Other names like “maliaro-chorto”, which means in Greek hairy herb, and “gerondas” (=oldman) refer instead to the plant morphology as its aerial parts arecovered by dense white hairs (Skoula and Kamenopoulos, 1997).

6. Ethnobotany, collection and cultivation

The herb of dittany consists of the dried or fresh aerial parts ofO. dictamnus, which are collected during the early summer period.More specifically, wild dittany is collected while in full bloom. Dur-ing its entire blooming period 2–4 different harvestings can takeplace. The first in the end of May, the second two months later afterthe name-celebration of Prophet Elias at the 20th of July, when theplant is “full of essential oil”, and the third in the end of August.According to other folkloric sources the best time for harvestingis supposed to be after the 17th of July (name-celebration of SaintMarina) (Fragaki, 1969).

Dittany is a species with significant commercial interest sinceit is widely used for herbal teas, not only in the local markets of



the island of Crete but all around Greece in traditional or modernshops and open-air market stalls (Skoula and Kamenopoulos, 1997;Hanlidou et al., 2004). In the past, the demand for plant materialwas covered only by the collection of wild populations, a fact whichlead to their rapid decrease and extinction from several areas of theisland (Skoula and Kamenopoulos, 1997).

The collectors of wild dittany were organised groups of localpeople called “Erontades”, “Atitanologi”, “Botanologi”, or “Mazoc-tades”, which travelled across the island in order to collect enoughplant material. The often climbing accidents, which occurred duringthe collection and the increasing demand for plant-material, drovethe locals towards the cultivation of the plant since 1920. Nowa-days, the cultivated plants are the main source of plant-materialused. Wild populations are under legal protection as a vulnera-ble species under the Revised Appendix 1 of the Bern Convention(2002). The populations within Samaria Gorge National park areprotected by law against collecting (Turland, 1995) as well. Thesystematic cultivation of O. dictamnus in several villages of Cretelike Kato Poros and Argirupoli started around 1920. In the begin-ning the local farmers, cultivated the plant in pots and in rockyplaces, but since 1928, when the cultivation spread all over Cretethey also tried cultivation in small fields close to the areas of thewild plant populations. After 1935, there was a rapid increase inits cultivation reaching a peak of 10 tonnes/year of total produc-tion. During the war cultivation was inhibited. Right after the endof the German occupation cultivation started again in the villagesof Heraclion estate by about 370 farmers in an area 500 acres andproduction reached 50 tonnes/year. The first farmers’ partnershipfor the production and trade of dittany was created around 1956and during 1964 there is a noted export of 24 tonnes of drieddittany from Heraclion port (Plimakis, 1997). The production of dit-tany reached its peak from 1980 to 1990 and is now in decline. In1991–2000 a portion of 85% of the product was exported (mainly toItaly, France, Germany and Japan), while 15% of the total productionwas absorbed by the Greek market. Abroad, main users of the prod-uct are distillery industries. At present, the intensive cultivation ofO. dictamnus has ceased and production has dropped to minimumlevels with the price fluctuating between 5.0 and 5.90D /kg. Only afew farmers still harvest O. dictamnus today and they do so mainlyfrom wild populations as this offers them an additional income,albeit low. Of the several reasons for the drop in dittany cultivation,the most important is the lack of a properly organized marketingsystem for such a crop (Skoula and Kamenopoulos, 1997).

Scientific data concerning the different ways of cultivation ofdittany, were sparse and mostly based on the local the farmers’experience. It is proposed that dittany can be cultivated in the samefield for up to 4 years, but according to the farmers’ long standingexperience, it would be much preferable, to replant every October.February and March are supposed to be the best period for plantingof the new dittany plants, while irrigation depends on the drynessof the soil. Farmers distinguish different types of plant cultivarssuch as (i) the “black” (green, less hairy, narrow leaved) and (ii)“white” (hairy, large leaved). These types of cultivars occur in sev-eral locations and they have not yet been related to environmentalconditions. Especially the “black” (narrow leaved) type is more aro-matic, yields more biomass per plant and requires more harvestingsince it is woodier, although it is more susceptible to pests duringstorage (Skoula and Kamenopoulos, 1997).

Several efforts for hydroponic cultivation of dittany have beenmade (mainly Nutrient Film Technique), with successful results(Economakis, 1992, 1993). Nowadays, there is a systematic culti-vation in several villages especially in Heraclion estate.

After harvesting, dittany is usually dried under mild condi-tions, in order not to harm the volatile constituents of its essentialoil. Usually the plant is left to dry in shadowy, well aired, dryplaces, in hanging little bunches or spread on grids. According

to the local farmers drying should not be done in plastic bagsor containers because the product is blackened. During dryingthe containing water decreases under the 10% of the total, whileplant weight decreases to the 2/3 of its initial weight (Plimakis,1997).

7. Phytochemistry

7.1. Chemical analysis of plant extracts

The lipid composition, of the dried and the fresh leaves ofO. dictamnus L. has been identified by Komaitis et al. (1988)and Revinthi-Moraiti et al. (1985), as well as a variety of non-polar components such us fatty acids, lipids, sterols and essentialoil.

A vast number of polyphenolic components, flavonoids andcoumarins have also been isolated and identified from themethanol extract of aerial parts of the plant (Harvala and Skaltsa,1986; Skaltsa and Harvala, 1987). Generally the extracts of O. dic-tamnus with polar solvents contain higher amounts of phenoliccompounds than the ones with non-polar solvents. The total phenolcontent of the O. dictamnus water, methanol, ethanol and acetoneextract has been identified as 21.7, 13.8, 7.7, 6.7 (meq/Lt) by Molleret al. (1999).

From the aqueous extract of O. dictamnus the following phenoliccompounds have been identified: !-coumaric acid (13.9%), ferulicacid (0.34%), hydrated catechin (0.5%) or catechin (0.22%) (Proestoset al., 2006, 2008).

Recently, from the polar extracts of the aerial parts of cul-tivated O. dictamnus one new depside has been isolated, towhich was given the trivial name salvianolic acid P, in addi-tion to the known depsides rosmarinic acid and rosmarinic acidmethylester, two monoterpenes: thymoquinone and thymoquinol2-O-ˇ-glucopyranoside; two simple phenolic acids: oresbiusin Aand E-caffeic acid; six flavonoids: apigenin, kaempferol, quercetin,eriodictyol, taxifolin, narigenin; and two alicyclic derivatives: 12-hydroxy jasmonic acid and its 12-O-ˇ-d-glucoside (Chatzopoulouet al., 2010).

Exploring the chemotaxonomic differences of genus Amara-cus Piozzi et al. (1986) isolated the following triterpenes fromthe aerial parts of Amaracus dictamnus Bentham (syn. Origanumdictamnus L.): oleanolic and the rare 21"-OH oleanolic acid, urso-lic acid and a new 21"-OH ursolic acid and also ouvaol. Duringthis study no diterpenic components were found in the ace-tone extract, a fact which was in contrast with previous findingsof the same group for Amaracus akhdarensis and A. pampaninii(Lamiaceae). The results of the above studies are summarized inTable 2.

7.2. Chemical analysis of essential oil

The plants belonging to the Lamiaceae family are well knownfor the production of essential oils (EOs). Essential oils are nor-mally formed in special cells or groups of cells like the glandularhairs already described for O. dictamnus by Bosabalidis and Tsekos(1982). They are aromatic, oily mixtures of volatile componentswith characteristic odour and taste. They usually consist of a greatnumber of different components, up to 150, with various chemicalformulas. Steam distillation is a cheap and commonly used methodfor producing EOs on commercial basis, while extraction by meansof liquid carbon dioxide under low temperature and high pressureis rarely used because it is more expensive (eventhough it producesa more natural organoleptic profile) (Burt, 2004). The majority ofthe data considering the chemical composition of O. dictamnus EOs’refer to the first method of extraction and usually for the produc-



Table 2Overview of chemical constituents isolated from different part of dittany.

Plant part Extract Reference

LipidsLipid composition (w/w% of plant material)

Total lipids 9.72%, non-polar lipids 7.68%: (81%of total lipids), polar lipids 1.85%: (19% of totallipids)

Dried leaves Revinthi-Moraiti et al. (1985)

Total lipids: 20%, non-polar lipids: 13.6% (68%of total lipids), polar lipids 6.38% (32% of totallipids)

Fresh leaves CHCl3/MeOH (2:1), CHCl3 Komaitis et al. (1988)

Lipid components identifiedSterols, steryl esters, fatty alcohols, free fatty

acids (palmitic, oleic, linoleic), waxes, traces oftriglyceride, sulpholipids, cerebrosides, mono-,di- and poly-digalactosyl diglycerides,phosphatidyl-ethanolamine, -serine, -glycerol,-inositol, -choline

Fresh, dried leaves Revinthi-Moraiti et al. (1985),Komaitis et al. (1988)

Phosphatidic acid Dried leaves Revinthi-Moraiti et al. (1985)

TriterpenesOleanolic, ursolic acid, uvaol, 21 "-OH oleanolicacid, 21 "-OH ursolic acid

Aerial parts Acetone Piozzi et al. (1986)

Triterpenic acids (ursolic) Fresh, dried leaves CHCl3/MeOH (2:1), CHCl3 Revinthi-Moraiti et al. (1985),Komaitis et al. (1988)

Polyphenols!-Coumaric acid (13.9%), ferulic acid (0.34%),hydrated catechin (0.5%), catechin (0.22%)

Dried leaves H2O, MeOH Proestos et al. (2006, 2008)

eriodictyol, apigenin, luteolin, quercetin Aerial parts MeOH (ethyl acetate fraction) Skaltsa and Harvala (1986, 1987)cosmoside, luteolin-7-glucoside, orientin,iso-orientin, vitexin, iso-vitexin,vicenin-2,aesculin .

Aerial parts MeOH (butanol fraction)

Thymoquinone, thymoquinol2-O-#-glucopyranoside, E-caffeic acid,salvianolic acid P, apigenin, kaempferol,quercetin, eriodictyol, taxifolin, narigenin,12-hydroxy jasmonic acid (alicyclic derivative)

Aerial parts MeOH Chatzopoulou et al. (2010)

Rosmarinic acid, rosmarinic acid methylester,oresbiusin A,12-O-#-D-hydroxyjasmonyl-glucopyranoside(alicyclic derivative)

Aerial parts MeOH/H2O (5:1)

tion of the EOs they use the aerial parts of the plant (Table 3) areused.

The so-called character of the essential oil is defined fromits major components. For O. dictamnus the major componentsof its essential oil are the monoterpenes: carvacrol, $-terpineneand p-cymene (Argyropoulou et al., 2009; Liolios et al., 2009;Chorianopoulos et al., 2004; Daferera et al., 2003; Daferera et al.,2002; Daferera et al., 2000; Figueredo et al., 2006; Economakis et al.,2005; Economakis et al., 2002; Economakis et al., 1999; Sivropoulouet al., 1996; Harvala et al., 1987; Katsiotis and Oikonomou, 1986;Scrubis, 1979; Schaden and Hesse, 1976). In most cases, carvacrolproved as the major component of the studied oils (Fig. 7), withp-cymene, $-terpinene and sometimes thymoquinone followingin amounts (Table 3). In only one case of cultivated O. dictamnus,thymol (isomer of carvacrol), has been revealed, as the dominantvolatile constituent of its essential oil, while carvacrol was totallyabsent (Daferera et al., 2000). The monoterpenes p-cymene and$-terpinene are the precursors of carvacrol and its isomer thymolin Origanum and Thymus species (Skoula et al., 1999). Although thecomposition of EOs can differ between different harvesting seasonsand between geographical sources, the sum of the amounts of thesefour compounds defines the character of the essential oil since inalmost all the specimens it ranges between 62 and 100% (Table 3).This is an observation proven true for most Greek oregano plantsderived from different geographical regions (Kokkini et al., 1997).

Hydroponic cultivations in Crete under different conditions alsorevealed carvacrol as main compound (33.5–89.0%) (Economakis etal., 1999, 2002, 2005).

8. Biological activities

8.1. Biological activities of O. dictamnus extracts

8.1.1. Antimicrobial activityThe water extracts of O. dictamnus and other plants from Lami-

aceae family have been tested vs. the yeast Yarrowia lipolytica.Dittany and rosemary extracts (concentration of 5 g extract/L)presented the greater lag time and the greater inhibition activ-ity against Yarrowia lipolytica compared to all the other extracts(Karanika et al., 2001).

The traditionally known use of the plant against gastric ulcers(Fournier, 1947; Berendes, 1902) was proved by in vitro tests. Theaqueous 70%/methanol extract was tested against one referencestrain of Helicobacter pylori and 15 clinical isolates of H. pylori (fromanthral biopsies). O. dictamnus and its close relatives, O. vulgare andO. majorana proved very active against the used Helicobacter strains.The minimal inhibition concentration (MIC) was also identified forthe extract (around 2.50 mg/ml for all but one strain) (Stamatis etal., 2003).

Moreover the methanol extract has been proved active againstthe Gram-negative clinical strains Acinetobacter haemolyticus,Empedobacter brevis, Pseudomonas aeruginosa and Klebsiella Pneu-monia (Chatzopoulou et al., 2010).

8.1.2. Antioxidative activityStudies conducted by the Umezawa method for various plants of

Lamiaceae family and among them O. dictamnus, have shown that


236 C.C. Liolios et al. / Journal of Ethnopharmacology 131 (2010) 229–241Ta

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Fig. 7. Graph representing carvacrol amount between recent studies on the EOs of O. dictamnus. (AP) aerial parts, (B) bracts, (L) leaves, (F) flowers, (NS) not specified, (HS)headspace analysis (Ex) CH2Cl2 extract, (C) cultivated, (W) wild, (HC) hydroponic cultivated, (P) platyphylus, (S) stenophylus.

its methanol extract has antioxidant action similar with a-tocoferol(Couladis et al., 2003).

Extracts of dittany of different polarities have been tested:(i) with electron spin resonance (ESR) spectrometry (16.5 %lextract/ml corresponding to 0.413 mg of dried spice/ml), for theirefficiencies as scavengers of free radicals and (ii) by measurementof oxygen depletion (12.5 mg dried spice/ml) in a methyl linoleateemulsion, for their efficiencies as chain breaking antioxidants. Thewater extracts showed high efficiency for both tests. The methanolextract was of medium efficiency, whereas the acetone extractshowed less activity in both assays. The methanol and water extractare rich in phenolic derivatives, contrary to the acetone extracts andthat is why they have greater efficiency as antioxidants (Molleret al., 1999). These results are of great importance for the foodindustry, because they open a new possibility, where natural prod-ucts like dittany, would potentially replace synthetic antioxidants(Economou et al., 1991). On the other hand Lionis et al. (1998) didnot report any significant antioxidant effect for the water extractof dittany by the lipid peroxidation assay when tested in culturedlung cells exposed to iron and ozon. Although more scientific dataare needed concerning the antioxidant ability of the polar dittanyextracts, the water extracts in general, seems to have the highestantioxidative ability. Thus the herbal tea of dittany, which is a waterextract, would be very beneficial for consumers.

The non-polar extracts of dittany have also been tested withpositive results. The cyclohexane extract has reported antioxi-dant efficiency as well as the ability to suppress the mutagenicityof Trp-P-2, a common dietary carcinogen. Also, in the unsaponi-fied fraction of dittany all the four known tocopherols (alpha-,beta-, gamma- and delta-tocopherols) have been determined, andespecially the concentration especially of gamma-tocopherol was

significantly higher. Total tocopherol content ranged from 288 to672 ppm (Lagouri and Boskou, 1996).

A recent study (Kouri et al., 2007) comparing the antioxidantscavenging activity against DPPH, between the non-polar and thepolar extracts of O. dictamnus (0.1 ml of extract), showed that themost polar ethanol extract (EtOHs) presented the highest activ-ity, followed by the DE (diethyl ether) and the EAc (ethyl acetate)extract, while the PE (petroleum ether) extract exerted a weakactivity. In the same study when the authors tested the protec-tive effect of each extract against the accelerated oxidation of oilthey found the opposite results, with EtOHs extract presenting noprotective effect, while PE, DE and EAc extracts protected the cot-tonseed oil significantly. The polar extract although rich in activeantioxidative compounds, like phenolic acids and flavonoid glyco-sides, could not incorporate them in the oil due to their hydrophobiccharacteristics.

8.1.3. Cytotoxic activityBased on preliminary bio-assays for the isolation of potentially

cytotoxic compounds various extracts of O. dictamnus were sub-mitted to pharmacological investigations. The dichloromethaneresidue showed an important in vitro cytotoxic activity, whileethanol and water extracts proved almost inactive. The bioassay-directed fractionation of the dichloromethane extract led tothe isolation and characterization of ursolic acid. The initialdichloromethane extract was tested according to NCI proce-dures and proved to be active in vitro ID50 = 8 and 14 %g/mlagainst P388 (murine leukemia) and human bronchial epider-moid cancer NSCLC-N6 (non-small cell lung cancer) cell linesrespectively. Ursolic acid exhibited a high activity in vitroagainst the same cell lines (ID50 = 3.5 and 9 %g/ml). Afterwards



in vivo experiments on murine ascite leukemia P388 exhib-ited a marginal anti-leukemia activity (T/C = 125% at 50 mg/kg).All in vivo tests were conducted on nude mice (Chinou et al.,2007). Ursolic acid isolated from Origanum vulgare ssp. hirtum(common oregano) is also known for its anti-thrombus activity(Goun et al., 2002; Sivropoulou et al., 1996).

8.2. Biological activities of O. dictamnus essential oil

8.2.1. Antimicrobial activityThe essential oils extracted from the plants of the Lamiaceae

family contain phenolic compounds, which are well known fortheir antimicrobial activities (Sivropoulou et al., 1996; Panizzi et al.,1993; Gergis et al., 1990; Pellecuer et al., 1980). Plants belongingto the genus Origanum are generally well known for the produc-tion of essential oils rich in phenolic compounds, like thymol andits isomer carvacrol. The essential oil of O. dictamnus is located inthe aerial parts of the plant i.e. bracts, leaves and flowers. Thereare controversial studies whether the essential oil from the bractshas stronger antimicrobial effect than the one from the leaves.According to current data, the antimicrobial action seems to dependupon the concentration of carvacrol, the percentage of which is alsodependant on the method of cultivation. Two different antimicro-bial studies have been conducted against Staphylococcus aureus, S.epidermidis, S. hominis: the first one has shown stronger antimicro-bial effect for the essential oil of the leaves while the second hasshown stronger antimicrobial activity for the essential oil of thebracts (Economakis et al., 1999, 2002).

A recent study (Liolios et al., 2009) determined the antimicro-bial activities of the oils from wild and cultivated plants as wellas of the pure substances carvacrol, thymol and their mixturescarvacrol/thymol (6:1) carvacrol/c-terpinene, before and after lipo-somal encapsulation by the diffusion technique (disc method). Thetests were conducted against four Gram positive bacteria: Staphy-lococcus. aureus, S. epidermidis, S. mutans and S. viridans, four Gramnegative bacteria: Penicillium aeruginosa, Escherichia coli, E. cloacaeand Klebsiella pneumoniae, three human pathogenic fungi: Can-dida albicans, C. tropicalis and C. glabrata, as well as against thefood-pathogen Listeria monocytogenes. The essential oils from bothassayed species (wild and cultivated specimen) showed compara-ble activities against all tested microbial strains. Pure compounds(carvacrol, thymol), proved more active than the oil, and theirantimicrobial activities were significantly increased after theirencapsulation in liposomes. Thymol exhibited stronger activitythan carvacrol, against most microbial types while no inhibitionwas found in controls, consisting of empty liposomes. Despite thefact that only a small quantity of carvacrol was encapsulated inliposomes it showed equal or improved activity than the pure com-pound at higher concentrations.

A dose-dependent inhibition against the mycelial growth ofPenicillium digitatum and conidial germination was observed byO. dictamnus essential oil. Mycelial growth was totally inhib-ited at 300 %g/mL, while complete inhibition of germination wasobserved at the concentration of 250 %g/mL (Daferera et al., 2000).A dose-dependent inhibition of mycelial growth was also observedfor Botrytis cinerea and Fusarium sp. The concentrations neededfor the total inhibition of the mycelia growth were 200 and250 %g/mL respectively. Additionally, the colony forming abilityof the bacterial pathogen of tomatoes, Clavibacter michiganensissubsp. michiganensis, was inhibited by 100 %g/mL of O. dictamnusessential oil. (Daferera et al., 2003).

The essential oil of O. dictamnus, shows antimicrobial actionagainst the phytopathogenic bacteria for potato tubers Erwiniacarotovora. This activity is also due to carvacrol (Vokou et al., 1993).

Antimicrobial activity of major essential oil compounds: carvacroland thymol. Carvacrol and thymol (the isomeric phenol of car-

vacrol), seem to possess strong antimicrobial activity, whereas theirbiosynthetic precursors: $-terpinene and p-cymene are inactive.The bacteria which showed positive results were: Staphylococcusaureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtillis,Rhizobium leguminosarum and Salmonella typhimurium. Both car-vacrol and thymol were inactive against P. aeruginosa. (Sivropoulouet al., 1996; Panizzi et al., 1993). Carvacrol in particular seemsto possess strong antibacterial activity against Bacillus cereus, aspore forming food born pathogen bacteria (Ultee et al., 1998)and it has also shown antifungal activity against Rhizopus (9species), Mucor (4 species), and Aspergillus (7 species) (Thompson,1989). A dose-dependent inhibition of the mycelial growth ofPenicillium digitatum was observed for carvacrol and thymol. Thefollowing values were reported for carvacrol and thymol for theconcentration causing 50% inhibition of radial growth (ED50):carvacrol ED50 = 47 %g/mL, thymol ED50 = 79 %g/mL. For minimalinhibitory concentration (MIC) the values reported were, car-vacrol MIC = 160 %g/mL and thymol MIC = 200 %g/mL (Dafereraet al., 2000). A similar previous study reported for carvacrolMIC = 125 %g/mL (Caccioni and Guizzardi, 1994).

Inhibition of DNA synthesis by Carvacrol. Carvacrol has also beenassessed using a cell proliferation assay using mouse myoblastcell line, CO25, bearing a mutated human N-ras oncogene. In vitrocytotoxicity of carvacrol reported was IC50 = 60 %g, while for theinhibition of DNS synthesis the dose was 10 %g/ml (Zeytinoglu etal., 2003).

8.2.2. Insecticidal effectThe essential oil of O. dictamnus, shows insecticidal effect against

Drosophila auraria. The essential oil was lethal for the 37–40% ofthe adult flies’ population after 24 h of exposure thought theirfood. After 48 h of exposure to the essential oil the eggs failed tohatch in a percentage less than 10–40% of the whole. Several kindsof malformation were observed to the dead and surviving larvaeand pupae, which indicates the strong toxic effect of the essen-tial oil during the insect’s development (Konstantopoulou et al.,1992).

8.3. Therapeutical uses

8.3.1. Known traditional uses (not supported by in vivoexperimental data)

Nowadays, as in the past, dittany is widely used in Crete asa traditional medicine. The aerial parts of the plants are beingused in various preparations against almost every illness and forthe maintenance of good health. The following data refer to themost common uses of these preparations according to the localvillagers and ethnographic literature (Plimakis, 1997; Skoula andKamenopoulos, 1997; Havakis, 1978; Fragaki, 1969; Steinmetz,1954).

Infusion: 20–30 g of plant material in 0.5–1 L hot water. Uses:tonic, anti-convulsion, against tonsillitis, cold, cough and sorethroats, diuretic, digestive, spasmolytic, against stomach and kid-ney discomforts. It has also been recommended traditionally,against liver diseases, diabetes and obesity.

Infusion/chewed crude plant parts: against gingivitis andtoothache and as emmenagogue and assisting childbirth (induc-tion delivery). Moreover it is considered as an abortifacient whileit is also lessens the abdominal pains (Skoula and Kamenopoulos,1997).

Decoction: 1.5–5 g of dried/fresh dittany in 250 ml (about oneglass) of boiling water. The plant should not be left for long intothe boiling water because its valuable components are destroyed.The decoction called ‘brastari’ in Crete should be used within 24 h,otherwise it is proved as useless. Dosage 2 cups per day. Uses:headaches, neuralgia, gingivitis and toothaches, tonsillitis and sore



throat, common cold and against cough. The decoction also hasbeen used for digestion against stomach-aches, as diuretic againstnephralgia and against arthritis. Finally it is considered to inducemenstruation.

Tincture: made with 15–30 g of dried or fresh herb in 1 L wineor “raki” (traditional Cretan drink) or 25% ethanol dilution. Uses:similar to the decoction.

Cutaneous use (used externally): compresses, powder, plantparts crushed with water. Uses: antiseptic, anti-inflammatory, anti-bleeding, cicatrizing, against bruises, carbuncles and ulcerations,against bad breath and sore throat, for wound healing and againstheadaches. Compresses on the underbelly are said to induce child-birth. It is also recorded as anti-epileptic.

Additionally a recent ethnopharmacological study, consideringthe herbs traded in the local markets of Thessaloniki, the follow-ing therapeutic uses for the aerial parts of the herb were reported,applied either by infusion or as an external application (cutaneoususe as a compress or by washing): endocrinal disorders – diabetes,gastrointestinal disorders – liver disorders, spasmolytic, stomachulcer, metabolic disorders – cholesterol, neuropsychiatric disorders– brain stimulant, headache, skin disorders – antiseptic, sanative,urogenital system – diuretic, dysmenorrhoea, other – antibacterialactivities, aphrodisiac, stimulant (Hanlidou et al., 2004).

8.3.2. Safety and pharmacologyAccording to the U.S.A. CFR (2009) O. dictamnus is characterised

as safe for consumption spice. This means that it can be used asa natural flavouring substance or adjuvant may as long as: (a) itis used in the minimum quantity required to produce its intendedphysical or technical effect and in accordance with all the prin-ciples of good manufacturing practice and (b) it is used in theappropriate forms (plant parts, fluid and solid extracts, concen-trates, absolutes, oils, gums, balsams, resins, oleoresins, waxes,and distillates) alone or in combination with other flavouring sub-stances and adjuvants also generally recognized as safe for fooduse.

Especially the essential oil of O. dictamnus can be added asflavouring in alcoholic beverages, usually around 21.00 ppm andmax 55.00 ppm (De Vincenzi et al., 2004; Fenaroli and Burdock,2004). Additionally, when it was given to rats, through in vivoexperiments, it was found to induce glutathione of S-transferase(GST) in some tissues. This particular enzyme is considered to haveprotective role against chemical mutagens (Lam and Zheng, 1991).Absorption kinetics and metabolism of the major component of theoil, carvacrol after per os administration in rats, rabbits and dogs hasbeen previously reported (Austgulen et al., 1987; Williams, 1959;Schroder and Vollmer, 1932), while the same parameters have beenstudied for thymol (Austgulen et al., 1987; Takada et al., 1979;Williams, 1959; Robbins, 1934) showing considerable similaritiesbetween them.

8.3.3. MutagenicityThere are no data considering the mutagenicity effect of the

plant extracts or its essential oil. The data considering carvacrol inthe Ames test are somewhat ambiguous. Carvacrol was marginallymore toxic to the repair-deficient E. coli strain than to its repairproficient counterpart. It also increased the relevant numbers inthe Ames test strain TA100, regardless of methanolic activation,but not to a level considered significant.

The positive results in SOS chromotest at high doses probablyreflect some secondary effect caused by the toxicity of this com-pound. In conclusion, the genotoxic potential of carvacrol is veryweak, although the possibility of its action at DNA level cannot beexcluded, because of the nuclear fragmentation that was observed(Stammati et al., 1999).

9. Conclusions

This review on the endemic plant of Crete O. dictamnus knownas dittany, attempts to shed light on the therapeutic poten-tial of the herbal tea as traditional herbal medicinal product, aswell as its commercial applications in distilleries and produc-tion of aromatic wine – liqueurs (Benedictine), since antiquity(Skoula and Kamenopoulos, 1997; Baumann, 1996). The histori-cal records for dittany’s various medicinal properties date backto ancient Greece, while nowadays it is still in use mainly asherbal tea, a well-known traditional medicine against various ill-nesses i.e. sore throat and cough, stomach ulcer, cholesterol, aswell as for its believed activities as: spasmolytic, brain stimu-lant, antiseptic, diuretic, antibacterial activities and aphrodisiac(Hanlidou et al., 2004; Plimakis, 1997). Some of those thera-peutic uses can be linked to specific ingredients, since theirmedicinal properties have been individually proven through inter-national literature (Fournier, 1947; Berendes, 1902; Skoula andKamenopoulos, 1997).

Especially the traditional use of dittany’s herbal tea against gas-tric ulcers (Fournier, 1947; Berendes, 1902), was studied throughin vitro assays on its aqueous 70% extract, chemically comparableto the herbal tea, which was found active against Helicobacter pylori(Stamatis et al., 2003). The above results could possibly be linkedto the high phenolic content of the water extracts of the leavesof the plant, and/or especially to its content in depsides, whichhave been recently isolated and determined (Chatzopoulou et al.,2010).

The published strong antimicrobial activities of the essentialoil of dittany (Liolios et al., 2009; Daferera et al., 2003, 2000;Economakis et al., 2002, 1999) could be linked to its high contentin carvacrol, and its isomer thymol, two phenols well known forsuch activity (Daferera et al., 2000; Ultee et al., 1998; Sivropoulouet al., 1996; Caccioni and Guizzardi, 1994; Panizzi et al., 1993;Thompson, 1989). The strong in vitro activity of the oil against thefood-pathogen Listeria monocytogenes has also been shown (Liolioset al., 2009). Moreover, the recently published strong antimicro-bial activity of the polyphenols isolated from the polar extractsagainst the Gram-negative clinical strains: Acinetobacter haemolyti-cus, Empedobacter brevis, Pseudomonas aeruginosa and Klebsiellapneumonia (Chatzopoulou et al., 2010) could also be linked to itstraditional medicinal uses against sore throat, toothache, gingivitis,tonsillitis. Dittany as a natural source of essential oil and pheno-lic components has attracted many investigators to evaluate theiractivity as antioxidants or free radical scavengers (Kouri et al., 2007;Couladis et al., 2003; Moller et al., 1999; Lagouri and Boskou, 1996;Economou et al., 1991). It is clear according to published resultsthat the EO and the extracts of the plant maybe considered aspotential natural antioxidant. Additionally, the antibacterial andantioxidant activity of O. dictamnus make it a potential safe foodadditive as flavour agent with numerous potential applications, inthe field of food, cosmetic and pharmaceutical industry as well asfood preservative.

Finally, it is noteworthy, that although the famous wound-healing activity of the herb has never been studied or provedexperimentally, it is still in use, according to all references throughcenturies, from antiquity (Minoan civilisation, Hippocrates andAristotle), till our days for the same indication, based on this long-standing traditional practise.

In conclusion, the recent scientific data and the rich histori-cal evidence concerning the various applications of O. dictamnuscould support its ethnomedicinal importance as well as its usesas a safe herbal medicinal product, while it remains essentialto document the existing traditional medical experience in com-bination with further relevant in vitro/in vivo pharmacologicalassays



Acknowledgements

A part of this work was presented by Christos Liolios (pharma-cist, MSc), in a National competition on “Dittany of Crete” whichwas held in Crete in 2004, and has been awarded with the first prizeby the Hellenic Society of Ethnopharmacology. The authors wish tothank as well, Mr J. Silignakis for kindly providing figures of dittanyfrom his personal archive and G. Sotiroudis (MSc Pharmacist) forhis help during the preparation of the manuscript.

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