Sàng lọc các cây thuốc có tiềm năng điều trị bệnh gút thông qua ức chế xanthin oxidase in vitro.pdf

B Y T

TRNG I HC DC H NI

TRN NGC YN CHI

SNG LC CC CY THUC C

TIM NNG IU TR BNH GT

THNG QUA C CH XANTHIN

OXIDASE IN VITRO

KHA LUN TT NGHIP DC S

Ngi hng dn:

1. T.S. Nguyn Thy Dng

2. T.S. Phng Thin Thng

Ni thc hin:

B mn Dc lc

H NI - 2013

LI CM N

hon thnh kho lun ny, ti nhn c s gip rt nhiu ca

thy c, bn b v ngi thn.

Trc tin ti xin by t lng bit n su sc ti TS. Nguyn Thu Dng

v TS. Phng Thin Thng, nhng ngi thy lun quan tm, gip ,

hng dn v ng vin ti trong sut qu trnh hon thnh ti ny.

Xin chn thnh cm n cc thy, c v cc anh ch k thut vin B mn

Dc lc gip v to iu kin cho ti trong sut qu trnh nghin cu v

thc hin ti.

Xin chn thnh cm n cc cn b phng o to, cc b mn, phng ban

khc ca trng i hc Dc H Ni.

Li cui cng, ti xin gi li cm n n gia nh v bn b, nhng ngi

lun lun ng vin, gip v ng gp kin cho ti hon thnh kho lun ny.

H Ni, thng 5, nm 2013.

Sinh vin

Trn Ngc Yn Chi

MC LC

LI CM N

MC LC

DANH MC CC CH VIT TT V K HIU

DANH MC CC BNG

DANH MC CC HNH

T VN .............................................................................................................1

CHNG 1. TNG QUAN .......................................................................................3

1.1. Vi nt v bnh gt & enzym xanthin oxidase .................................................3

1.1.1. Khi nim v c ch bnh sinh bnh gt ....................................................3

1.1.2. Mi lin quan gia bnh gt v enzym xanthin oxidase ............................4

1.1.3. Enzym xanthin oxidase ..............................................................................5

1.2. Mt s thuc v dc liu c tc dng c ch XO ...........................................7

1.2.1. Cc thuc c ch XO ang c lu hnh .................................................7

1.2.2. Cc nghin cu v pht trin dc liu c tim nng c ch XO ..............9

CHNG 2: I TNG, PHNG TIN V PHNG PHP NGHIN

CU ..........................................................................................................................14

2.1. Nguyn liu nghin cu ..................................................................................14

2.2. Phng tin nghin cu ..................................................................................14

2.2.1. Ho cht, thuc th ..................................................................................14

2.2.2. Dng c v thit b th nghim .................................................................15

2.3. Ni dung nghin cu.......................................................................................15

2.4. Phng php nghin cu ................................................................................16

2.4.1. Phng php thu thp mu v thng tin cc cy thuc a vo sng lc 16

2.4.2. Phng php chit xut dc liu ............................................................16

2.4.3. Phng php nh gi nh hng ca cc mu th ln hot XO .......17

2.4.4. Phng php x l s liu ........................................................................19

3.1. Kt qu ............................................................................................................20

3.1.1. Kt qu thu thp d liu v cc dc liu a vo sng lc ....................20

3.1.2. Kt qu sng lc tc dng c ch XO in vitro ca cc dc liu ............44

3.1.3. Xc nh IC50 ca cc dc liu tim nng c ch XO ............................63

3.2. Bn lun ..........................................................................................................63

3.2.1. V thng tin ca cc cy thuc a vo nghin cu ................................63

3.2.2. V kt qu sng lc tc dng c ch XO in vitro trn a Costar 96 ging

............................................................................................................................64

3.2.3. V kh nng c ch XO ca cy thuc tim nng ...................................65

KT LUN ...............................................................................................................67

1. Kt lun ..............................................................................................................67

2. xut ...............................................................................................................67

TI LIU THAM KHO

PH LC

DANH MC CC CH VIT TT V K HIU

XO : Xanthin oxidase

XDH : Xanthin dehydrogenase

Oxh : Oxy ho

CCTT : Cha c thng tin

HMD : iu ho min dich

HA : Huyt p

DANH MC CC BNG

STT K

hiu Tn bng Trang

1 2.1 B tr th nghim trong tng ging 18

2 3.1 Thng tin v cc dc liu sng lc 21

3 3.2

nh hng ca cc dch chit ln hot XO in vitro ti

cc nng 100 g/ml, 50 g/ml, 10 g/ml hn hp phn

ng

45

4 3.3 IC50 ca cc dc liu tim nng c ch XO 63

DANH MC CC HNH

STT K hiu Tn hnh Trang

1 1.1 Qu trnh chuyn ho purin trong c th 4

1

T VN

T lu, cc sn phm t nhin ng vai tr quan trng trong iu tr bnh.

Trong hai thp k qua c 30,2 % cc loi thuc mi c ph duyt c ngun

gc t t nhin [72]. Cng vi s i mi trong cc phng php iu tr bng cc

sn phm t nhin, cy thuc v cc ch phm chit xut t thc vt c quan

tm nhiu hn bi nhng u im so vi ho dc [114]. Cc thuc theo y hc hin

i thng c tc dng nhanh, hiu qu tng i tt. Tuy nhin, khi dng tn dc

iu tr cc bnh mn tnh li bc l nhc im nhiu tc dng khng mong

mun v gi thnh cao khi dng lu di. Gt l bnh ri lon chuyn ho mn tnh.

Ngi b bnh gt phi i mt vi vic s phi s dng thuc trong thi gian di

v c th gp nhiu vn m cc thuc tn dc mang li. Do , nhiu nghin

cu v thuc c ngun gc t dc liu c a ra khc phc cc nhc

im nu trn.

Bnh gt gn lin vi tng acid uric mu v mc tiu chnh trong iu tr l

lm gim lng acid uric trong mu. Acid uric huyt thanh l sn phm cui cng

ca qu trnh chuyn ho purin qua trung gian l xanthin oxidase (XO), mt loi

enzym oxy ho hypoxanthin thnh xanthin v xanthin thnh acid uric. Vic s dng

cc cht c ch enzym XO cn tr hnh thnh acid uric trong c th l mt mc

tiu m cc nghin cu v ang hng ti. Vi truyn thng lu i v y hc c

truyn, vi nhng kinh nghim dn gian v s dng cy c lm thuc t cc dn tc

khc nhau trong nc, Vit Nam c mt ngun dc liu phong ph v cn cha

c khai thc nhiu. T thc t , gp phn sng lc nhm tm kim cc dc

liu c kh nng c ch XO, bc u trong qu trnh xc nh dc liu tim nng

iu tr gt, ti: Sng lc cc cy thuc c tim nng iu tr bnh gt thng

qua c ch xanthin oxidase in vitro c thc hin vi ba mc tiu sau:

1. Thu thp c thng tin ca mt s cy thuc Vit Nam c tim nng khai

thc.

2

2. Sng lc c cc cy thuc c tim nng iu tr gt thng qua con ng

c ch xanthin oxidase in vitro trn a 96 ging.

3. Xc nh IC50 ca cc cy thuc c tim nng c ch XO.

3

CHNG 1. TNG QUAN

1.1. Vi nt v bnh gt & enzym xanthin oxidase

1.1.1. Khi nim v c ch bnh sinh bnh gt

1.1.1.1. Khi nim

Gt l bnh ri lon chuyn ho cc nhn purin, c c im chnh l tng

acid uric mu. Tnh trng vim khp trong bnh gt l do s lng ng cc tinh th

monosolium urat trong dch khp hoc m [9].

1.1.1.2. C ch bnh sinh bnh gt

Bnh gt xut hin khi c th tch lu acid uric qu mc (gp vi ln bnh

thng). Nguyn nhn l do sn xut acid uric qu mc hoc gim thi tr acid uric.

Tng acid uric qu mc c th do s bt thng ca mt s h enzym tc

ng vo qu trnh chuyn ho purin nh tng hot tnh phosphoribosyl

pyrophosphat (PRPP) synthetase dn n tng nng PRPP - cht quan trng

trong qu trnh tng hp purin hay thiu ht hypoxanthin-guanin phosphoribosyl

transferase (HGPRT) - enzym chu trch nhim chuyn guanin thnh guanylic acid

v chuyn hypoxanthin thnh inosinic acid.

Hin tng gim thi tr acid uric thn vi hu ht cc bnh nhn gt (80-

90%) u khng r nguyn nhn (tng acid uric mu t pht). Thng thng, nu

sn xut acid uric cn bng vi thi tr th acid uric khng b tch ly. Tuy nhin,

bnh nhn gt lng thi tr t hn nhiu so vi lng acid uric sinh ra dn n

tng lng tinh th natri urat ha tan trong mu [36].

Khi nng acid uric tng cao s gy lng ng cc tinh th urat ti m to

nn cc ht tophi. Khi cc ht tophi ti sn khp b v s khi pht cn gt cp, s

lng ng vi tinh th cnh khp, mng hot dch, trong m sn v m xng s dn

n bnh xng khp mn tnh do gt. S c mt vi tinh th urat ti m mm, bao

gn to nn ht tophi; vim thn k l do tinh th urat lng ng ti t chc k ca

thn; acid uric niu tng v s toan ho nc tiu dn n si tit niu [9].

4

1.1.2. Mi lin quan gia bnh gt v enzym xanthin oxidase

Acid uric l sn phm cui cng ca qu trnh chuyn ho cc nucleoprotein

c cha nhn purin trong c th [1]. Cc purin c to ra chuyn ho thnh

hypoxanthin v xanthin, di tc dng ca enzym XO, chng c oxy ho thnh

acid uric. Qu trnh chuyn ho base purin trong c th c miu t trong hnh

1.1. [36].

Hnh1.1. Chuyn ho purin trong c th.

synthetase

PRPP PRPP

+ Glutamin

Inosinic acid Adenylic acid

Nucleic

acid

Guanylic

acid

Nucleic

acid

iu ha

ngc c ch iu ha

ngc c ch

Guanin Hypoxanthin PRPP

Xanthin oxidase

+

Xanthin

Acid uric

Ribose 5-phosphat

HGPRTase

PR

PP

HG

PR

Tas

e

5

Bnh gt c mi quan h cht ch vi nng acid uric mu. Khi nng

acid uric mu tng cao s lm tng nguy c mc bnh. Bn cnh , enzym XO c

vai tr ch cht trong qu trnh iu ho nng acid uric mu. Do vy, c ch

enzym XO l mt trong cc c ch chnh m cc thuc iu tr gt ang hng ti.

1.1.3. Enzym xanthin oxidase

1.1.3.1. V tr, c im l ho v c im cu trc

- V tr phn b

Enzym XO c tm thy nhiu loi ng vt c v, chim, cn trng v vi

khun [11]. Trong cc m ng vt c v, XO c phn b rng ri gan, rut,

thn, phi, tim, no, huyt tng, hng cu v cc m khc, trong gan v rut

hot ng XO l ln nht [21]. ngi XO c tm thy trong hu ht cc t bo

ca c th, tuy nhin n c nhiu nht trong cc t bo gan v cc t bo rut [17].

- c im l ho

XO c khi lng phn t l 275kDa. N b c ch bi cc ion kim loi

nng, ur cng nh rt nhiu purin, pyrimidin v cc hp cht d vng khc nh

purin-6-aldehyd, 2-amino-4-hydroxypteridin-6-aldehyd Enzym c pH ti u l

4,7 [11]. EDTA, histidin c cho vo qu trnh chit xut enzym bo v enzym

trong sut qu trnh phn ng [84].

- c im cu trc:

XO l mt protein c 2 tiu n v ging nhau. Mi tiu n v gm 4 trung

tm oxi ho kh 1 Molybdopterin (85kDa), 1 FAD (40kDa) v 2 Fe2S2 (20kDa).

Mo-co bao gm 1 dn xut pterin hu c (molydopterin), c cha 1 chui dithiolen

cng 1 nguyn t Mo [21], [95], [109].

Trnh t aminoacid rt tng ng trong enzym ca loi chut v tng

ng khong 90% gia loi chut vi con ngi [21].

6

1.1.3.2.Mt s phng php xc nh hot enzym

- Phng php o quang

+ Phng php o quang da trn lng acid uric to thnh t qu trnh

oxy ha xanthin di xc tc ca XO theo phn ng :

Xanthin + H2O + O2 2O2

T lng acid to thnh c o bc sng 290nm 25oC, pH = 7,5 hoc

8,0 xc nh c hot XO [93].

+ Phng php o quang s dng ABTS (2,2-azino-bis(3-

ethylbenzothiazolin-6-sulphonat) [79]:

Nguyn tc phn ng:

Hypoxanthin + 2 H2O+ 2 O2 2O2

Acid uric + O2 alantonin + H2O2 + CO2

H2O2 + ABTSred ABTSOX + 2 H2O

T lng ABTSOX to thnh o quang bc sng 410 nm xc nh c

hot XO.

- Phng php o p

xc nh hot enzym c th nh gi s kh ca cc cht nhn

electron l oxy, xanh methylen v cytochromC.

Nguyn tc ca phng php da trn o t l oxi tiu th vi c cht

xanthin, oxy c o p 37oC [35].

- Mt s phng php khc:

o hunh quang ca isoxanthopterin c to thnh: Hot ng ca XDH v

XO c th c phn tch hunh quang bng cch s dng qu trnh oxy ho pterin

thnh isoxanthopterin nh bin php kch thch hot ng enzym bc sng

345nm v pht x ti 390nm. T l oxy ho pterin c xc nh bi s vng mt

v hin din ca cht nhn electron xanh methylen t nh gi hot ng ca

XDH v XO tng ng [21].

7

Xc nh hot ng enzym bng cch nh lng H2O2 c to thnh trong

qu trnh hydroxyl ho xanthin bi XO. Flavin c kh phn ng vi O2 to thnh

H2O2 [21].

o oxy tiu th: Phn ng xanthin/XO c nghin cu bng cch o thi

gian lin tc ca oxy s dng bng 1 in cc chn lc [21].

1.2. Mt s thuc v dc liu c tc dng c ch XO

1.2.1. Cc thuc c ch XO ang c lu hnh

Allopurinol v febuxostat l hai thuc in hnh c tc dng c ch XO hin

ang c s dng trong iu tr.

1.2.1.1. Allopurinol

Allopurinol l cht u tin c xc nh c kh nng c ch XO v by

gi vn l thuc iu tr tng acid uric mu thng c s dng.

- Tc dng v c ch tc dng

Tc dng [3], [24]:

Thuc c ch XO, ngn chn s tng hp urat t hypoxanthin v xanthin do

lm gim lng acid uric trong mu.

Khi khng dng allopurinol, purin thi tr qua nc tiu di dng acid uric.

Khi dng thuc, purin trong nc tiu s tn ti 3 dng: acid uric, hypoxanthin v

xanthin. Mi cht c tan ring nn kt qu l lm tng lng thi tr purin qua

nc tiu, gim nng urat v acid uric huyt tng m khng lm ng niu

b tip xc vi mt lng acid uric qu ln.

Allopurinol lm gim acid uric mu di tan gii hn nn gip ha tan

cc ht tophi v ngn nga s tin trin ca vim khp mn do gt. Ngoi ra, acid

uric mu gim cng lm gim s hnh thnh si, ngn nga tin trin bnh v thn.

C ch:

Allopurinol lm h acid uric mu thng qua c ch enzym XO. Trong qu

trnh c ch enzym, allopurinol c hydro ho thnh alloxanthin (oxypurinol),

chng phi hp cht ch vi cc trung tm Mo b kh to thnh phc hp khng

8

hot ng [82]. nng thp, allopurinol l c cht v l cht c ch cnh tranh,

nng cao hn, n l cht c ch khng cnh tranh [95].

- u im

Thuc c dng nhiu hn cc thuc gy tng thi acid uric mu do c th

dng c trn hu ht bnh nhn, dng mt ln mt ngy v t l gp tc dng

khng mong mun t hn [62].

Thuc lm tng bi xut cc tin cht ca acid uric qua nc tiu nn t gy

si thn v cn au qun thn hn [3].

Ngoi iu tr gt, allopurinol cn c s dng phi hp iu tr cc loi

thiu mu cc b, tn thng mch mu v suy tim mn ci thin hot ng bt

thng ca ni m v lm gim cc du hiu stress oxy ho [65], [95].

- Nhc im

Khung cu trc ca allopurinol v oxypurinol c nhn purin v pyrimidin,

chu trch nhim cho mt s tc dng khng mong mun ca allopurinol [95].

Cc tc dng khng mong mun ph bin nht ca allopurinol l au d dy,

phn ng qu mn v pht ban da [95]. Hi chng qu mn ca allopurinol c

trng bi st, pht ban, vim gan, tng bch cu v suy chc nng thn [69]. Cc

tc dng ny thng xy ra nhng ngi suy gim chc nng thn, cha c

hiu chnh liu allopurinol [95].

1.3.1.2. Febuxostat

Febuxostat ln lt c C quan qun l thuc Chu u - EMEA v

Cc qun l Thc phm v dc phm Hoa K - FDA thng qua iu tr di hn

tng acid uric mn tnh trn bnh nhn gt [18], [23].

- Tc dng v c ch tc dng:

Febuxostat lm h acid uric mu bng cch c ch chn lc XO. Febuxostat

khng c nhn purin. Khng ging nh oxypurinol ch gn cht vi dng kh XO,

febuxostat gn vi c dng kh v dng oxy ho ca enzym. Febuxostat gn vi

knh di v hp dn n molypden-pterin lm che khut v tr gn ca c cht, t

c ch hot ng ca enzym [47].

9

- u im:

So vi allopurinol, febuxostat t gy d ng hn, hiu lc mnh hn khi la

chn cho bnh nhn khng ung c allopurinol hoc cc thuc iu tr bnh gt

khc. Thuc hu ch vi 5-10% ngi c hin tng qu mn vi allopurinol

cng nh nhng ngi suy thn khng th dng liu allopurinol [107].

Febuxostat khng c purin trong cu trc. Tuy c ch XO ging allopurinol

nhng febuxostat khng c ch cc enzym khc trong con ng chuyn ho purin

v pyrimidin [107], [47]. Do , thuc t gy hin tng qu mn hn allopurinol.

Febuxostat ch yu chuyn ho qua gan. V vy, thuc c th khng cn phi

iu chnh mc liu ngi suy thn nh allopurinol [107].

- Nhc im

Trong cc nghin cu thc hin, febuxostat an ton hn allopurinol. Tuy

nhin, y l thuc mi, kinh nghim s dng cha nhiu. V vy, cc tng tc

thuc cng nh cc tc dng khng mong mun ca thuc cn phi tip tc c

nghin cu [107].

1.2.2. Cc nghin cu v pht trin dc liu c tim nng c ch XO

Allopurinol v febuxostat l 2 thuc tn dc in hnh trong iu tr gt

mn. Hiu qu iu tr tt l nhng u im ni bt ca hai thuc trn. Tuy nhin,

chng c nhiu tc dng khng mong mun ng lo ngi. V vy, cc dc liu

iu tr gt theo c ch c ch XO vn ang c tip tc pht trin khc phc

nhc im trn.

1.2.2.1. Cc hng nghin cu trn th gii

Nghin cu sng lc in vitro l bc u t c th nghin cu theo

nh hng tc dng sinh hc v nh gi su hn khng nh tc dng trn m

hnh gy bnh trn ng vt thc nghim ca cc dc liu c kh nng c ch XO

mnh nht.

Trn th gii, hng nghin cu sng lc in vitro v dc liu cng nh cc

hot cht t dc liu tm kim ngun thay th vi hiu qu c ch enzym XO

tng t hoc vt tri hn ng thi t gy tc dng ph nghim trng hn

10

allopurinol c quan tm pht trin. Ngy cng c nhiu nghin cu c thc

hin khp cc nc trn th gii nh Australia, Vit Nam, Cng ho Sc,

Paraguay, Panama, Philippin, Trung Quc, n v cho nhng kt qu kh

quan [94], [114], [67], [121], [48], [20], [40], [90].

Lin quan n tc dng c ch XO in vitro, 3 hng tip cn ch yu ca cc

nghin cu c thc hin bi cc nhm nghin cu khc nhau trn th gii v

sng lc dc liu v cc cht/nhm hp cht phn lp t dc liu.

- Tip cn sng lc da trn kinh nghim s dng dc liu trong dn gian

hoc nn y hc c truyn ca mt s nc.

Hng tip cn th nht kh ph bin v c thc hin nhiu nc trn

th gii. Hng tip cn ny tp trung sng lc cc loi thuc cc h khc nhau da

trn kinh nghim dn gian hoc nn y hc c truyn cc nc t tm ra cc

cy thuc c tim nng nht. Nm 1998, tc dng c ch XO c kho st trn

26 loi thuc 18 h theo truyn thng c s dng iu tr bnh gt v cc triu

chng lin quan ca ngi dn bn a ca vng ng bc Bc M. Khong 88%

cc cy c tm thy c hot tnh c ch 100 g/ml, vi 20% c s c ch ln

hn 50%. Larix laricina c kh nng c ch cao nht l 86,33% [94].

Trong mt nghin cu khc, 28 dch chit t 17 loi thc vt bn a

Australia c kho st, dch chit Stemodia grossa, Eremophila maculata c tc

dng mnh nht vi IC50 < 50 g/ml [114].

Nm 2000, 122 cy thuc dn gian Trung Quc c la chn da trn

hiu qu lm sng v tn s k n iu tr bnh gt, tng acid uric mu v cc

ri lon lin quan khc nh gi tc dng c ch XO. Kong v cng s pht

hin 69 dch chit methanol v 40 dch chit nc c ch trn 50% hot XO

nng 100 g/ml. Kh nng c ch ln nht l dch chit methanol ca cnh l

Cinnamomum cassia (Lauraceae) (IC50 = 18 g/ml), tip n l hoa ca cy

Chrysanthemum indicum (Asteraceae) (IC50 = 22 g/ml) v l Lycopus europaeus

(Lamiatae) (IC50 = 26 g/ml. Vi cc dch chit nc, thn r ca Polygonum

cuspidatum (Polygonaceae) c ch enzym XO mnh nht (IC50 = 38 g/ml). Tuy

11

nhin, trong nghin cu ny, chng vn yu hn nhiu so vi allopurinol (IC50 =

1,06 g/ml) [67].

Nm 2006, tc dng c ch XO c kho st trn 6 dc liu vi 18 dch

chit nc, methanol v hn hp nc-methanol thuc cc h khc nhau ca ngi

dn bn a n . Trong 18 dch chit c 14 dch chit c ch XO 100 g/ml.

Trong c 10 dch chit c ch ln hn 50%. Sau , cc dch chit methanol ca

Coccinia grandis (IC50 = 29,79 g/ml), Datura metel (IC50 = 76,75 g/ml, Strychnos

nux-vomica (IC50 = 6,8 g/ml) v Vitex negundo (IC50 = 78,5 g/ml) c th

nghim in vivo chut [121].

Nm 2010, nghin cu in vitro kh nng c ch XO ca cc cy c s

dng trong dn gian ca Cng ho Sc v khu vc min Trung, ng u c

tin hnh vi 27 cy thuc, gm 84 dch chit ethanol v methylen clorid. Trong

dch chit ethanol - methylen clorid ca Populus nigra v Betula pendula c ch

mnh nht vi IC50 tng ng l 8,3 v 25,9 g/ml. Tip l dch chit 80%

ethanol Caryophyllus aromaticus v Hypericum perforatum c IC50 di 50 g/ml

[48].

Nm 2011, Apaya v cng s nh gi kh nng c ch XO ca dch chit t

15 dc liu c s dng vi tc dng chng vim trong y hc c truyn

Philippin. Kt qu cho thy 5 dc liu c tc dng c ch trn 50% nng 100

g/ml, tuy nhin tim lc yu hn nhiu so vi allopurinol [20].

- Tip cn sng lc theo h hoc chi thc vt

Hng nghin cu th 2 c mt s tc gi la chn sng lc tc dng

c ch ca cc dc liu thuc mt hoc mt s h in hnh. Hng nghin cu

ny tp trung nghin cu su theo mt h, mt s h hoc chi nht nh xc nh

cy thuc c tim nng nht. Trong dn gian, cc h ny c s dng ph bin vi

tc dng gim au, chng vim.

Nm 1988, mt nghin cu ca Paraguay c tin hnh trn h Sim

(Myrtaceae) trong Hexachlamys edulis l dc liu c ch XO mnh nht vi

IC50 = 5,5 g/ml [118]. Ti Panama, 9 loi ca h Dy gi (Celastraceae) v h Hoa

12

mi (Lamiaceace) c kho st v dch chit ethanol ca Hyptis obtusiflora

(Lamiaceae) v Hyptis lantanaefolia (Lamiaceae) c kh nng c ch cao nht,

khong 40% nng 1 g/ml [44]. Cc dc liu ca Brazil trong chi

Lychnophoras h Cc (Asteraceae) c s dng nh thuc gim au chng vim

trong dn gian c nghin cu. Trong s , Lychnophora trichocarpha,

Lychnophora ericoides, Lychnophoriopsis candelabrumv Lychnophora staavioides

l 4 dc liu c kh nng c ch mnh nht [40].

- Tip cn sng lc theo nhm hp cht phn lp t dc liu

Hng tip cn th 3 i su vo hp cht trong cc nhm hp cht t nhin

c phn lp t tm ra cht c tc dng c ch mnh nht. Flavonoid,

polyphenol, coumarin l nhng cht c nh gi k lng [75], [31], [26]. in

hnh nht l cc flavonoid vi rt nhiu nghin cu. Trong tng s 2092 flavonoid

t c s d liu, Lim v cc cng s la chn c 2 flavonoid l myricetin v

luteolin c tc dng c ch XO tt vi IC50 tng ng l 62,7 v 3,39 g/ml [72].

Bn cnh , nghin cu v mi lin quan cu trc-tc dng sinh hc ca cc hp

cht flavonoid nh apigenin, quercetin, myricetin, isovitexin, genistein v

naringenin cng c thc hin. Kt qu cho thy, apigenin l cht c ch mnh

nht, tng tc thun li nht vi trung tm hot ng enzym. Tip theo l

quercetin, myricetin, genistein v isovitexin. Naringenin khng cho thy s c ch

vi IC50 > 50 M [75].

1.2.2.2. Cc nghin cu ca cc tc gi Vit Nam

Vi ngun ti nguyn dc liu phong ph v nhng kinh nghim lu i s

dng cy c lm thuc, cc nh khoa hc Vit Nam cng thc hin cc nghin

cu sng lc, bc u cho kt qu kh quan. Nm 2004, Nguyn Th Thanh Mai

v cng s thc hin nghin cu theo nh hng sng lc dc liu c tim

nng c ch XO t ngun dc liu Vit Nam vi 288 dch chit t 96 cy thuc

c s dng trong y hc c truyn. Kt qu cho thy nng 100 g/ml, 46 dch

chit c s c ch ln hn 50% hot tnh enzym. 50 g/ml, 21 dch chit c ch

hn 50%. 25 g/ml, 8 dch chit cho thy c ch hn 50%, trong khi ti nng

13

10 g/ml, 2 dch chit c s c ch ln hn 50%. Cc dch chit methanol ca

Artemisia vulgaris (Ngi cu), Caesalpinia sappan (T mc), Blumea balsamifera

(i bi), Chrysanthemum sinense (Cc hoa) v dch chit methanol-nc ca

Tetracera scandens (Dy chiu) c kh nng c ch XO mnh vi IC50 < 20 g/ml.

Dch chit methanol t hoa Chrysanthemum sinense c kh nng c ch mnh nht

vi gi tr IC50 = 5,1 g/ml [86]. T c s sng lc , cc cy c nghin cu

su hn. T rut g ca cy Caesalpinia sappanphn lp c 17 hp cht t nhin

trong c 9 hp cht c tc dng c ch XO vi IC50 dao ng t 3,9 n 93,2

M. Hp cht c tc dng mnh nht l sappanchalcon vi IC50 = 3,9 M [87].

Nghin cu ho thc vt t cy Chrysanthemum sinense phn lp c mt flavon

glycosid mi l acacetin 7-O-(3-O-acetyl-beta-D-glucopyranoside) v 27 hp cht

bit khc bao gm flavonoid, dn cht ca acid caffeoyl quinic, monoterpenoid

glycosid. Cc hp cht ny c hot tnh c ch XO mnh hn allopurinol (IC50

=2,5 M) vi IC50 dao ng t 0,13-2,31 M [88]. Trong s 8 hp cht c phn

lp t dch chit methanol ca cy Blumea balsamifera c mt dihydroflanovol mi

th hin kh nng c ch mnh nht vi IC50 = 0,23 0,01 M [89]. Gn y nht,

t dc liu Tetracera scandens phn lp c mt hp cht nor-lupan triterpen

mi l 28-O- -D-glucopyranosyl ester ca acid platonic vi kh nng c ch XO

mnh vi IC50 = 1,9 M [90].

Trong khun kh ti ny, hng tip cn th nht s c ng dng

sng lc dc liu c tim nng iu tr gt thng qua c ch XO t ngun dc

liu thu thp t d n Bo tn ngun cy thuc c truyn ca Vin Dc liu. T

, ti hi vng tm ra dc liu c kh nng c ch XO mnh nht v a vo

nghin cu su hn.

14

CHNG 2: I TNG, PHNG TIN V PHNG

PHP NGHIN CU

2.1. Nguyn liu nghin cu

2.1.1. Dc liu nghin cu

Dc liu nghin cu gm 202 cy thuc c thu hi ti Vit Nam theo d

n Bo tn ngun cy thuc c truyn ca Vin Dc liu [4].

2.1.2. Chun b mu nghin cu

Cc mu dc liu sau khi thu hi c ra sch, phi hoc sy kh ri

trong ti polyethylen. Bo qun cc mu trong iu kin kh ro, thong mt,

trnh nh sng, mi mt, mc. Khng s dng ho cht bo qun mu.

Dc liu c xay th, c chit xut thnh dng cn methanol ton phn.

Chun b mu th cho th nghim in vitro: cn c ho tan trong dimethyl

sulfoxid (DMSO), c pha long bng m thnh cc nng 100 g/ml, 50

g/ml, 10 g/ml thc hin cc phn ng enzym.

2.2. Phng tin nghin cu

2.2.1. Ho cht, thuc th

Allopurinol (Sigma Aldrich).

Xanthin 99% (Sigma Aldrich).

Xanthin oxidase (9 n v/mg protein, 8 mg protein/ml, Sigma Aldrich).

Dimethyl sulfoxid (Merck).

Na2HPO4.2 H2O (Vel).

KH2PO4 (Vel).

HCl, NaOH (t tiu chun phn tch).

Cc ha cht v dung mi khc s dng trong nghin cu t tiu chun

dc dng.

15

2.2.2. Dng c v thit b th nghim

My o pH (EUTECH).

My ly tm (HERMLE Z300).

My siu m (Power sonic 405).

H thng my ELISA gm my c khay vi tinh th (Biotek, Hoa K) & my

lc khay (Awareness, Hoa K).

My ct nc 2 ln (Halminton, Hoa K).

Thit b khuy t (Heidolph, c).

Cn phn tch AY 220 (SHIMADZU).

96 y phng Costar 3596 (Corning, Hoa K).

u cn, pipet, micropipet, microtube cc loi.

2.3. Ni dung nghin cu

t c cc mc tiu nghin cu t ra, ti c thit k vi cc

ni dung sau:

Thc hin mc tiu 1: Thu thp c thng tin cc cy thuc a vo nghin

cu.

Xc nh tn khoa hc, b phn dng.

Tra cu thng tin v tc dng ca dc liu da trn cc ti

liu tham kho.

Thc hin mc tiu 2: Sng lc cc dc liu c kh nng c ch XO.

Chun b mu th in vitro.

nh gi kh nng c ch ca cc mu th 3 nng 100

g/ml, 50 g/ml v 10 g/ml.

Thc hin mc tiu 3: Xc nh c IC50 ca cc cy thuc c tim nng c

ch XO.

Kho st kh nng c ch ca cc mu th tim nng cc

nng khc nhau xc nh IC50.

16

2.4. Phng php nghin cu

2.4.1. Phng php thu thp mu v thng tin cc cy thuc a vo sng lc

Thng tin v tn cy, b phn dng, tn khoa hc c xc nh bi nhm

thc hin D n Bo tn cy thuc c truyn. Vic nh danh tn khoa hc ca

mu dc liu do c nhn Ng Vn Tri, Vin Dc liu v mt s chuyn gia v

thc vt xc nh. Mu tiu bn hoc mu cy c lu gi ti Vin Dc liu.

Thng tin v tc dng ca cc cy thuc c thu thp t cc ngun d liu:

sch Nhng cy thuc v v thuc Vit Nam ca Tt Li [10], sch Dc liu

hc tp 2 ca nh xut bn Y hc [2] v cc tp ch khoa hc t ngun c s d liu

Pubmed, Science direct v Wiley.

Mt s dc liu c s dng trong dn gian v y hc c truyn cha c

nghin cu v thnh phn ho hc cng nh hot tnh sinh hc. Trong cng vic

thc hin D n Bo tn ngun cy thuc c truyn, nhm thc hin thu hi mu

cy, lm tiu bn, chp nh, v nh m s dc liu xc nh tn khoa hc. Cc

mu dc liu thu hi c th xc nh ngay c tn khoa hc, cng c th cha

xc nh ngay c tn khoa hc m cn c thi gian tra cu, tham kho ti liu

v cc chuyn gia v thc vt hc. Sau khi xc nh c tn khoa hc th nhm

nghin cu s xem xt c th c bin php bo tn hay pht trin cy thuc.

thi im hin ti, a s cc cy thuc c tn a phng, tn khoa hc, b phn

dng, tc dng, nhng cng c nhng cy thuc cha c nhng thng tin ny.

2.4.2. Phng php chit xut dc liu

Cn 100 g mu dc liu sy kh cho vo bnh cu 1 lt, thm m vi

MeOH ri tip tc MeOH ngp dc liu khong 3 cm. Chit (2 ln) hi lu

cch thu trong 2 gi, lc qua giy lc ly dch chit. C dch chit c cn

MeOH ton phn.

17

Mt s dc liu c 2 mu th l cn methanol t cc b phn khc nhau ca

cng mt cy. Nhm nghin cu cng thu hi mt s mu dc liu cng mt loi

(cng tn khoa hc) nhng c thu hi ti cc a phng khc nhau kho st

s khc nhau ca cc dc liu theo vng min.

2.4.3. Phng php nh gi nh hng ca cc mu th ln hot XO

2.4.3.1. Nguyn tc

XO xc tc cho qu trnh oxy ha xanthin thnh acid uric.

Xanthin + O2 + H2O Uric acid + H2O2

Hot XO t l vi lng acid uric c nh lng bng phng php o

quang bc sng 290nm.

2.4.3.2. Chun b ho cht v cht th

m phosphat 70 mM, pH = 7,5.

Xanthin oxidase 0,04 U/ml: pha t XO 7 U/ml bng m phosphat.

C cht xanthin 260 M.

Dung dch HCl 1M dng phn ng.

Dung dch allopurinol 0,5 g/ml.

Mu th: Cn methanol ca cc mu cy c ho tan trong dimethyl

sulfoxid (DMSO). Sau cc mu th c pha trong m cc nng

100 g/ml, 50 g/ml, 10 g/ml.

2.4.3.3. Tin hnh

Th nghim c thc hin trn a 96 ging.

B tr trong mt a gm c: mu chng, mu i chiu (allopurinol) v mu

th.

B tr hn hp th trong tng ging c th hin bng 2.1.

18

Bng 2.1. B tr th nghim trong tng ging

Mu chng Mu i chiu Mu th

Dung dch th 0 0 20l

Allopurinol 0 20l 0

Dung dch m

phosphat 85l 65l 65l

Xanthin 60l 60l 60l

XO 30l 30l (sau HCl) 30l

HCl 25l 25l 25l

Tng th tch 200l 200l 200l

Hn hp th bao gm:

20l dung dch th.

65l dung dch m phosphat 70mM, pH = 7,5.

30l dung dch enzym (0,04 U/ml trong dung dch m phoshat

70mM pH = 7,5) c chun b ngay trc khi s dng.

Sau khi 25oC trong 15 pht, thm 60l xanthin 260M ri

25oC trong 30 pht.

Phn ng ngng li bng cch cho thm 25l HCl 1N v o hp

th 290nm.

Mu trng ca chng, i chiu v cc mu th cng c chun b

song song nh trn nhng enzym c thm vo sau HCl 1N.

Mi mu c th 3 nng 100 g/ml, 50 g/ml, 10 g/ml (trong ging).

Mi nng c tin hnh th 3 ln, ng vi mi nng tnh c 3 gi tr

OD v tnh trung bnh % c ch t 3 gi tr o c.

19

Tc dng c ch enzymXO c tnh theo cng thc [6], [104].

OD chng = ACT-AC ; OD th = AST-AS

Phn trm c ch XO = I% = [1 OD th / OD chng] x 100

Trong : AC l hp th ca mu chng

ACT l hp th ca mu trng ca chng

AS l hp th ca mu th

AST l hp th ca mu trng ca th.

2.4.3.4. Xc nh IC50 ca cc cy c tim nng c ch XO

Tc dng c ch XO ca cc cy c la chn c nh gi theo tr s

IC50, l gi tr nng (tnh ton theo l thuyt) ti mu th c ch 50% s to

thnh acid uric trong hn hp phn ng so vi mu chng [5].

Vi tng mu th c la chn, thit lp dy nng kho st t xc

nh IC50 v gii hn khong tin cy.

2.4.4. Phng php x l s liu

S liu c d tr bng phn mm Microsoft Excel Mac 2011 v tnh trung

bnh I% cc nng 100 g/ml, 50 g/ml, 10 g/ml bng Microsoft Excel Mac

2011. Gi tr OD dc biu din di dng M SD (M: gi tr OD trung bnh

tng mu, SD: lch chun), so snh gi tr trung bnh ca cc mu bng one-way

ANOVA, dng hu kim Dunnett test so snh gi tr trung bnh ca OD mu

th so vi mu chng. Tnh IC50 v khong tin cy 95% ca IC50 bng phng php

phn tch hi quy probit trn phn mm SPSS 16.0.

20

CHNG 3. KT QU V BN LUN

3.1. Kt qu

3.1.1. Kt qu thu thp d liu v cc dc liu a vo sng lc

Thu hi c 202 mu cy ti Vit Nam theo d n Bo tn ngun cy

thuc c truyn ca Vin Dc liu.

Thng tin v tn a phng, tn khoa hc, h, b phn dng v tc dng

dc l c th hin trong bng 3.1.

Nhn xt:

202 mu cy thuc 74 h v 187 loi, trong :

- 27 mu cy cha c thng tin v h.

- 81 mu cy cha c thng tin v tc dng.

- 13 mu cy cha c thng tin v b phn dng.

- 20 mu cy t 10 loi thu hi cc ni khc nhau (ph lc 3.1).

- 10 mu cy khc b phn dng t 5 loi (ph lc 3.2).

- Mt s mu ch c m s, cha c thng tin v tn cy, h, b phn dng v

tc dng.

21

Bng 3.1. Thng tin v cc dc liu c sng lc

STT M Tn ph thng Tn khoa hc H KH B phn

dng Tc dng

Cc cy thuc thu hi ti vn quc gia Bch M, tnh Tha Thin Hu

1

Tm gi nghin Vaccinium bullatum Ericaceae Thn CCTT

2 Mng lng CCTT CCTT CCTT CCTT

3

Thanh long Hylocerus andatus Castaceae thn chng oxh

[19]

4

Xuyn Cudrania tricuspidata Carr. Bur Moraceae cnh, l chng vim,

oxh [129]

5

Vng cch Premna corymbosa Rottl. ex Willd Verbenaceae cnh l thp khp

[61]

6 CT42 Cu ng Uncaria acida Hunt. Roxb. Rubiaceae cnh c

mc CCTT

7 CT22 Me rng Phyllanthus emblica L. Euphorbiaceae trn mt

t h HA[10]

8 CT40 Gai Bohmeria nivea L. Gaud. Urticaceae l r:chng

vim [74]

22


dng Tc dng

9 CT26 Kim cang qu to Smilax megacarpa A.DC. Smilacaceae thn r CCTT

10

Bo sm Hibiscus sagistifolius Malvaceae thn r bo v d

dy [13]

11 CT29 Sn thuyn Syzygium resinosum (Garnep.) Merr.

et Perry Myrtaceae l

khng khun

[7]

12

T bi bin Vitex trifolia L f. Verbenaceae cnh, l gim au[10]

13 CT03 An in lng Hedyotis hirsuta Spreng. Rubiaceae c cy CCTT

14 CT34 V hng dai Stemonurus coriaceus Miers Icacinaceae cnh, l CCTT

15 CT33 Thi t Paederia consimilis Pierre ex Pitard Rubiaceae cnh l CCTT

16 CT35 Kinh gii r Elsholtzia penduliflora W.W. Smith Lamiaceae trn mt

t CCTT

17 CT01 Cu tri, Can tri Phyllanthus chamaepeuce Ridl. Euphorbiaceae ton cy CCTT

18 CT43 Bch b Stemona tuberosa Lour. Stemonaceae r, l, thn ho [10]

19 CT18 C 2 l Solanum diphyllum L. Solanaceae ton cy chng oxh

[51]

20 CT21 CCTT Sp Acanthaceae CCTT CCTT

23


dng Tc dng

21 CT25 Bt ch lng Glochidion eriocarpum Champ. Euphorbiaceae cnh, l ph thn [10]

22 CT04 CCTT CCTT CCTT CCTT CCTT

23 CT41 Lng mc ng Wrightia dubia Spreng. Apocynaceae L c tb ung

th [91]

24 CT16 L men Mosla dianthera Maxim. Lamiaceae ton cy RLTH [10]

25 CT15 Tm phong Cardiospermum halicacabum L. Sapindaceae ton cy chng vim,

oxh [52]

26 CT34 V hng dai Stemonurus coriaceus Miers Icacinaceae cnh, l CCTT

27 CT13 Pht d mnh Dracaena gracilis Wall. ex Hook.f. Dracaenaceae r CCTT

28 CT17 B my Clerodendrum cyrtophyllum Tucz Verbenaceae trn mt

t

st pht ban

[10]

29 CT44 Cu ng l hnh tim Uncaria cordata

Lour. Merr. Rubiaceae

on thn

c mc CCTT

30 CT10 Kim cang poilane Smilax poilanei Gagnep. Smilacaceae thn r CCTT

31 CT06 Lin ng hoa nh Illigera parviflora Dunn Hernandiaceae CCTT cy tm Dao

[12]

24


dng Tc dng

32 CT19 Bng bong Lygodium scandens Lygodiaceae dy thn

mang l CCTT

33 CT36 Mua b Melastoma sanguineum

Sims Melastomataceae cnh, l

qu: chng

oxh [41]

34 CT07 Kim cang Smilax corbularia Kunth Smilacaceae thn, r chng vim

[105]

35 CT08 H th trng Streptocaulon juventas

Lour. Merr. Asclepidaceae thn r

c tb ung

th [120]

36 CT11 L khi Ardisia gigantifolia Stapf Myrsinaceae l c tb ung

th [76]

37 CT32 Xun hoa Pseuderanthemum

bracteatum Acanthaceae l CCTT

38 CT51 Bm bc campuchia Mussaenda cambodiana Pierre ex

Pitard Rubiaceae

cnh, l,

hoa

hoa: li tiu

[10]

39 CT02 An in Hedyotis hedyotidea

DC. Merr. Rubiaceae ton cy

chng vim

[99]

25


dng Tc dng

40 CT38 Lu Psychotria rubra Poir. Rubiaecae thn, l c tb ung

th [49]

41 CT31 Bm bc hoa dy Mussaenda densiflora Li Rubiaceae cnh l CCTT

42 CT09 Chng chng Smilax perfoliata Lour. Smilacaceae thn r cha thp

khp [97]

43 CT28 Cch lng vng Premna fulva Craib Verbenaceae cnh, l cha vim

khp [92]

44 CT52 Quyn b Selaginella uncinata Desv. Spring Selaginellaceae ton cy

chng thiu

oxy huyt

[138]

45 CT48 An in trng Hedyotis ovata Thwaites ex Hook.f. Rubiaceae cnh, l CCTT

46 CT30 Thng sn Dichroa febrifuga Lour. Hydrangeaceae l r: chng

vim [30]

47 CT27 Song giam Leptonichia acuminatus Mast. Sterculiaceae l CCTT

48 CT37 Mua lng Melastoma saigonense Merr. Melastomataceae cnh, l CCTT

26


dng Tc dng

Cc cy thuc thu hi ti Sapa, tnh Lo Cai

49 CT14 Hng bi Dianella ensifolia L. DC. Liliaceae CCTT c [10]

50 CT49 Kim cang l bc to Smilax bracteata Presl Smilacaceae thn , r chng oxh

[136]

51 MC8 Kim tuyn Sapa Anoectochilus roxburghii Wall. Orchidaceae ton cy chng oxh

[32]

52 CT47 D cm Hedyotis capitellata var. mollis

T.N.Ninh Rubiaceae

phn trn

mt t

chng oxh

[16]

53 MC1 Cy xuyn l Cancora petelotii Gentiliaceae ton cy CCTT

54 MC4 Tai th Dipterocarpus sp. Dipterocarpaceae qu chng vim

[130]

55 CT50 Mc chm Wrightia laevis Hook.f. Appocynaceae cnh, l CCTT

56 MC2 Trm tu CCTT CCTT CCTT CCTT

57 CT23 M t t hoa Rhynchodia pauciflora Pitard Apocynaceae cnh, l CCTT

58 CT20 Gi hc bng Leea aequata L. Leeaceae R CCTT

59 MC7 Thch sng hoa tm Cynoglossum zeylanicum Boraginaceae c cy CCTT

27


dng Tc dng

60 MC3 Mi chng Chinacanthus nutans Acanthaceae cnh, l chng oxh

[132]

61 S19 H kh tho Prunella vulgaris L. Lamiaceae cm hoa

qu gi

h huyt p

[10]

62 CT58 Ch ch Parashorea chinensis Wang Hsie. Dipterocarpaceae qu CCTT

63 CT53 Thi thanh Alangium kurzii Craib. Alangiaceae thn, l CCTT

Cc cy thuc thu hi ti Ba V, thnh ph H Ni

64 CT55 Tiu ba v Piper bavinum C.DC. Piperaceae phn trn

mt t CCTT

65 MC6 M mt Isotoma longiflora Lobeliaceae phn trn

mt t CCTT

66 CT54 Chi mi gn lm Antidesma montanum Bl. Euphorbiaceae thn, l chng vim

[73]

67 CT56 Vt vng nht Viburnum lutescens Bl. Caprifoliaceae phn trn

mt t

CCTT

28


dng Tc dng

68 CT60 L ni Hydnocarpus kurzii Warb. Flacourtiaceae phn trn

mt t CCTT

69 CT57 C di hoa trng Solanum torvum Swartz. Solanaceae thn, l tr nt n[10]

70 CT61 Cm chy Sambucus javanica Reinw. Ex Blume Caprifoliaceae cnh mang

l, hoa li tiu [10]

71

Lc lc l i Crotalaria assamica Benth Fabaceae cnh mang

l

chng vim

[66]

72 S12 Thc lp l ln Desmodium sequax Wall. Fabaceae phn trn

mt t CCTT

73 CT64 G Afzelia xylocarpa Craib. Fabaceae ht CCTT

74 CT65 T chu lng d hnh Callicarpa heterotricha Merr. Verbenaceae cnh, l CCTT

75 CT62 Mi liu Miliusa balansae Fin. & Gagnep. Annonaceae cnh, l c tb ung

th [55]

76 CT59 Mu ch l nh Knema globularia Warb. Myristicaceae ht CCTT

77 S 6 CCTT CCTT CCTT CCTT CCTT

29


dng Tc dng

78 CT79 T kn ci Helicteres hirsuta Lour. Sterculiaceae l c tb ung

th [29]

79 S17 Ban l nh Hypericum uralum Thumb. Hypericaceae. cnh non,

l CCTT

80 CT84 T chu Callicarpa rubella Verbenaceae ton cy chng ung

th [46]

81 S 8 Duc c Derris pachyloba Fabaceae thn, l CCTT

82 S 2 Gic mc t gn Cornus oligophlebia Merr. Cornaceae cnh, l CCTT

83 CT85 Trm thon Sterculia lanceolata Cav. Sterculiaceae thn tr sng

ty[10]

84 S 13 Cu ng cnh leo Uncaria scandens Smith Hutch. CCTT on cnh

c mc CCTT

85 S 3 Hoa khoe cy nho gc Sabia parviflora Wall. ex Rox Sabiaceae r chng

vim[112]

86 S 14 Tiu rng Piper sp. Piperaceae trn mt

t

chng oxh

[15]

30


dng Tc dng

87 S 5 Cm Itoa orientalis Flacourtiaceae l chng nm

[117]

88 S 4 Cm chy Sambucus javanica Reinw. Caprifoliaceae cnh, l li tiu [10]

89 Cam ni Toddalia asiatica L. Lamk. Rutaceae cnh, l chng oxh

[110]

90 CT46 Cu ng l ln Uncaria macrophylla Wall. ex Roxb. Rubiaceae cnh, l gin mch

[125]

91 S 1 Nc nc Oroxylum indicum Bignoniaceae v thn chng d ng

[10]

92 S 20 Lc lc l i di Crotalaria assamica

Benth Fabaceae cnh, l

r: chng

vim [66]

93 CT87 Thn linh l to Kibatalia macrophylla Woodson Apocynaceae thn, l CCTT

94 S 15 Dm dng hoc Epimedium macranthun Mooren et

Decne. Berbridaceae c cy

chng vim

[133],[10]

95 S 11 Mt gu Rhabdosia sp. Lamiaceae CCTT CCTT

31


dng Tc dng

96 S 18 Ban trn Hypericum patulum Ham. Ex. D.Don Hypericaceae cnh mang

l, hoa

c tb ung

th [123]

97 CT80 Rung Mallotus apelta Muell.-Arg. Euphorbiaceae r, thn bo v gan

[128]

98 CT68 Chn Microdesmis casearifolia Pandaceae thn, l CCTT

99 CT86 Cm lng Eleaocarpus nitidus Jack Eleaocarpaceae l CCTT

100 CT75 Mung trung Zanthoxylum avicennae DC. Rutaceae thn, l chng vim

[27]

101 CT81 Si trng Sapium sebiferum Roxb. Euphorbiaceae cnh, l chng vim,

oxh [42]

102 BV55 Ma d Costus speciosus Koenig Sm. Costaceae thn r chng oxh

[37]

103 BV56 V ch Ficus heterophyllus L Moraceae thn, l cha phong

thp [10]

104 CT72 ngn Cratoxylum pruniflorum Kurz Hypericaceae cnh, l CCTT

32


dng Tc dng

105 CT88 a bp b Ficus nervosa Moraceae thn, l

r: khng vi

khun lao

[28]

106 CT67 Mu ch thanh Knema elegans Warb. Myristicaceae ht c tb ung

th [34]

107 CT83 Gi hc Leea rubra Blunne Leeaceae r h HA [22]

108 CT66 Chi mi m Antidesma ambiguum Pax & Hoffm Euphorbiaceae cnh non,

l CCTT

109 CT76 V san l di Osmanthus pedulculatus Gagnep. Oleaceae cnh, l CCTT

110 CT77 CCTT sp1 Magnoliaceae CCTT CCTT

111 CT82 Ca l bc Caryodaphnosis tonkinensis Airy-

Shaw Lauraceae cnh, l CCTT

112 CT69 Chn Microdesmis casearifolia Planch. ex

Hook Pandaceae thn, l CCTT

113 CT74 Chi mi Antidesma ghaesembilla Gaertn Euphorbiaceae cnh non,

l CCTT

33


dng Tc dng

114 CT71 Xoan nh Choerospondias axillaris Burtt. &

Hill Anacardiaceae v thn

qu: chng

oxh [124]

115 CT70 i khoai Aidia oxyodontaYamazaki Rubiaecae CCTT CCTT

116 BV52 Thin nin kin Homalomena occulta Lour schott Araceae thn r chng oxh

[139]

117 BV49 Long no Cinnamomum camphora Lauraceae l chng vim,

oxh [71]

118 CT78 Kim cang l mng Smilax riparia A.DC. Smilacaceae thn r gin ph

qun [113]

119 BV34 Con kh Pseuderanthemum palatiferum Nees

Radlk Acanthaceae l CCTT

120 BV60 Ba kch Morinda officinalis How Rubiaceae thn r chng oxh

[134]

121 T12-11 C the Centipeda minima L A.Br.et Aschers Asteraceae ton cy

chng vim,

oxh [54],

[73]

34


dng Tc dng

122 BV48 C gi t Balanophora sp. Balanophoraceae cnh, l chng oxh

[126]

123 BV47 Hong lin Coptis teeta Wall Ranumculaceae thn r khng khun

[10]

124 BV51 C gi t Balanophora sp. Balanophoraceae phn trn

mt t

chng oxh

[126]

125 BV42 Rt Hex godajam Colebr. ex. Well. Hicaceae v CCTT

126 BV44 Liu l (hng ch) Ocimum basilicum L. Lamiaceae l, cnh

mang hoa

chng vim

ty [10]

127 BV40 Rt Hex godajam Colebr. ex. Well. Hicaceae. l CCTT

128 BV0 Cm rng Ehretia acuminata Boraginaceae cnh, l CCTT

129 BV58 Chui ht Musra barjoo Sieb. Musaceae qu xanh CCTT

130 Bv30 Thc lp Tadehagi triquetrum L. Fabaceae phn trn

mt t

tr giun

[127]

35


dng Tc dng

131 BV24 L khi Ardisia silvestris Myrtaceae l cha au d

dy [45]

132 CT73 Thu mt Balansa Bridelia balansae Euphorbiaceae thn, l long m

[111]

133 BV59 C ry Houltuynia cocdata Thumb Saururaceae thn r CCTT

134 CT24 Hng b di Clausena excavata Burm.f. Rutaceae cnh, l HMD [81]

135 BV36 Khm p Ixora spp. CCTT cnh, l khng khun

[70]

136 BV35 C dm Stephania dielsiana Y.C.Wu Menispermaceae c CCTT

137 BV39 Chc mu Salacia cochinchinensis Celastraceae thn r tr T [8]

138 T12_12 Mi ch nhiu Ammania baccifera L. Lytraceae CCTT CCTT

139 T12_02 T xanh Cassytha filiformis L. Lauraceae ton cy chng oxh

[103]

140 BV57 V ch Ficus heterophyllus L. Moraceae phn trn

mt t.

cha phong

thp [10]

36


dng Tc dng

141 T12_09 Lc tin Passiflora foetida L. Pasihoraceae phn trn

mt t an thn [2]

142 T12_03 Sm lng Eurya ciliata Merr L. Theaceae Cnh, l chng long

xng [116]

143 BV33 Tm kho my

(dy ct kh) Ventilago leiocarpa Benth. Rhamnaceae.

phn trn

mt t

chng vim

[25]

144 T12_01 Ci xay Abutilon indicum L Sweet Malvaceae cnh l

mang qu

chng vim

[119]

145 T12_07 N qu trng Flueggea virosa Roxb ex Willd Voigt Euphorbiaceae l chng co git

[98]

146 BV28 C bit toan CCTT CCTT CCTT CCTT

147 BV26 Cm ru(qu xanh) Glycosmis pentaphylla Correa Rutaceae cnh, l bo v gan

[85]

148 T12_05 Chm rng Strobilanthes cystolithigera Lindau CCTT cnh, l CCTT

149 BV17 Xui lim(r r) Homonoia riparia Lour. Euphorbiaceae r , g, l chng st rt

[91]

37


dng Tc dng

150 T12_04 Dy sm ni cao Cyclea fansipanensis Gagnep Menispermaceae thn r

thuc tm

ngi Dao

[12]

151 BV37 Ma d Costus speciosus Koenig Sm. Costaceae thn chng oxh

[37]

Cc cy thuc thu hi ti Vn quc gia Phong Nha - K Bng, tnh Qung Bnh

152 BV01 Sm cau Curculigo orchioides Gaertr Hypoxidaceae thn r chng vim

[68]

153 BV02 a lin Kaempferia galanga L. Zingiberaceae thn r chng vim

[122]

154 BV04 Cm rng l nhn Ehretia acuminata Boraginaceae cnh, l CCTT

155 BV05 Thc lp Desmodium rodgeri Schindl. Ohashi CCTT cnh, l tr giun

[127]

156 BV10 m m hoa trng Rubus leucanthus Hance CCTT cnh, l CCTT

38


dng Tc dng

157 BV11 Gai Boehmeria nivea L. Gaud. Urticaceae l r: chng

vim [74]

158 BV12 Chn chim Scheffena octophylla Lour Araliaceae thn, r v

l

h ng

huyt [10]

159 BV13 Si rng Sarcandra glabra Thunb. Nakai CCTT phn trn

mt t

chng oxh

[57]

160 BV15 Ngy hng Rubus cochinchinensis Tratt. CCTT thn vim gan

[10]

161 BV16 Ry leo Pothos scandens L. Araceae thn, l chng oxh

[106]

162 BV19 X en Ehretia asperrula Zoll & Mor Boraginaceae thn, cnh,

l

chng oxh

[77]

163 BV20 Li tin Stephania longa Lour. CCTT dy thn,

l

chng vim

[135]

39


dng Tc dng

164 BV21 Ngng chan hy( kh rng) Rourea minor Gaertn Leenh. Connaraceae cnh non,

l

chng st rt

[50]

165 BV22 Ng v Nam Kadsura heteroclita Roxb. Craib CCTT thn chng oxh

[131]

166 BV06 Kng ba (Dy m g) Limacia scandes Lour. Menispermaceae thn, l chng trm

cm [64]

167 BV25 Khi ta Ardisia silvestris Pitard CCTT l

cha au

bng,d dy

[45]

168 BV29 Ba gc Rauvolfia verticilata Lour. Bail Apocynaceae r H HA [2]

169 BV31 Bm bc Mussaenda cambodiana Pierre ex

Pitard CCTT thn, l

hoa: li tiu

[10]

170 BV38 Thin nin kin Homalomena occulta Lour schott Araceae thn r chng oxh

[139]

171 BV41 Mu ngi Mucuna pruriens L. DC. CCTT thn chng oxh

[14]

40


dng Tc dng

172 BV43 C hi Solanum erianthum D.Don Solanaceae cnh l

mang hoa

khng khun,

c tb [38]

173 BV50 T tn Asarum balansae Franch. CCTT phn trn

mt t CCTT

174 BV53 B khai Erythropalum scandens Blume CCTT c cy chng vim

[83]

175 BV61 Sm cau l rng Curculigo latifolia Dryand. ex Ait. CCTT thn r i tho

ng [59]

176 T12_08 Cao cng Ophiopogon reptans Hook Convallariaceae thn r

cy tm

ngi Dao

[12]

177 T12_10 Sn kim Anisomeles indica

L. Kuntze Lamiaceae

trn mt

t

chng vim

[104]

178 CT92 Sang trng Ardisia gracillima Myrsinaceae trn mt

t CCTT

41


dng Tc dng

179 CT97 Mung trung Zanthoxylum avicennae DC. Rutaceae CCTT

chng vim

[27]

180 CT97 Mc chim Amalocalyse miceolobus

Pierre ex Spire Apocynaceae cnh l CCTT

181 T12_13 Xo tam phn Paramygnya petebotii Guill. Rutaceae cnh, l CCTT

182 BV03 Si nht Chloranthus japonicas Sieb Chloranthaceae r c tb ung

th [39]

183 BV07 C thp bt Equisetum diffusum D.Don CCTT phn trn

mt t li tiu [60]

184 BV08 a sn Ilex glomerata King CCTT cnh, l CCTT

185 BV09 Xun hoa Pseuderanthemum palatiferum Nees.

Radlk. CCTT cnh, l h HA [63]

186 BV14 C ry xanh Iodes cirrhosa Turcz. Menispermaceae phn trn

mt t

chng vim

[43]

42


dng Tc dng

187 BV18 Chm ta Strobilanthes mucronatoproductus CCTT cnh, l CCTT

188 BV23 M hoa Clerodendrum paniculatum L. CCTT cnh, l CCTT

189 BV27 R qut Belamcanda chinensis L. DC. CCTT thn r chng oxh

[58]

190 BV32 Bng bong do Lygodium flexuosum L. Sw. CCTT c cy chng

vim[33]

191 BV46 Da di Pandanus tinctorius Pandaceae thn gim m

mu [137]

192 CT90 Ba chc Euodia lepta Rutaceae cnh l CCTT

193 CT91 Li tru choi Tabernaemontana buffalina Apocynaceae phn trn

mt t CCTT

194 CT93 C sa to l Euphorbia hirta L. Apocynaceae phn trn

mt t CCTT

195 CT94 Xng m nguyn Carallia brachiata Rhizophoraceae cnh, l c ch XO

[100]

43


dng Tc dng

196 CT95 Thu kn l hp Helicteres angustifolia Sterculiaceae cnh, l

chng oxh

[53], chng

vim [73]

197 CT96 Dy au xng Tinospora sinensis Menispermaceae cnh l HMD[80]

198 CT99 Tu hoa Genianthus laurifolius Asclepidaceae cnh, l CCTT

199 CT101 Chy hoa sng Strobilanthes apricus Acanthaceae cnh, l CCTT

200 CT102 S Alseodaphne sp. Lauraceae v thn CCTT

201 CT103 Bi bung Acronychia pedunculata Rutaceae cnh, l c ch COX-

2 [96]

202 CT104 Bp lng Actinodaphne pilosa Merr. Lauraceae cnh, l CCTT

Ch thch: CCTT: Cha c thng tin, oxh: oxy ha, tb: t bo, HMD: iu ha min dch

44

3.1.2. Kt qu sng lc tc dng c ch XO in vitro ca cc dc liu

p dng m hnh vi 3 mc nng : 100 g/ml, 50 g/ml, 10 g/ml

cho tt c dch chit ca cc mu th nh gi nh hng ln hot XO in

vitro.

Kt qu c th hin trong bng 3.2.

Nhn xt:

- Ti nng 100 g/ml c 20 mu c tc dng c ch XO, c 1 mu c

ch > 50%.

- Ti nng 50 g/ml c 13 mu c tc dng c ch XO, khng c mu

no c ch > 50%.

- Ti nng 10 g/ml c 3 mu c tc dng c ch XO, khng c mu

no c ch > 50%.

45

Bng 3.2. nh hng ca cc dch chit ln hot XO in vitro ti cc nng 100 g/ml, 50 g/ml, 10 g/ml hn hp phn ng

STT Tn khoa hc

% c ch XO

Nng 100 g/ml Nng 50 g/ml Nng 10 g/ml

OD I% OD I% OD I%

1 Vaccinium bullatum 0,544 0,038 6,10 0,393 0,024 6,87 0,406 0,071 6,88

2 CCTT 0,546 0,01 5,69 0,429 0,026 - 0,446 0,081 -

3 Hylocerus andatus 0,489 0,029 15,5 0,396 0,026 6,10 0,434 0,085 0,458

4 Cudrania tricuspidata (Carr.) Bur 0,577 0,023 0,35 0,410 0,033 2,38 0,381 0,098 12,6

5 Premna corymbosa Rottl.Ex

Willd

0,513 0,029

11,4 0,372 0,048 11,43 0,377 0,092 13,5

6 Uncaria acida Hunt. Roxb. 0,507 0,032 12,4 0,410 0,035 2,38 0,411 0,103 5,73

7 Phyllanthus emblica L. 0,53 0,04 8,46 0,413 0,026 1,67 0,447 0,085 -

8 Bohmeria nivea L. Gaud. 0,454 0,054 21,6 0,400 0,028 4,76 0,41 0,08* 5,96

9 Smilax megacarpa A.DC. 0,494 0,026 14,7 0,414 0,027 1,43 0,393 0,076 9,86

10 Hibiscus sagistifolius 0,446 0,058 22,9 0,419 0,033 0,238 0,434 0,079 0,458

46

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

11 Syzygium resinosum Garnep.

Merr. et Perry 0,54 0,007 6,73 0,426 0,036 - 0,447 0,096 -

12 Vitex trifolia L f. 0,564 0,028 2,59 0,433 0,030 - 0,41 0,089 5,96

13 Hedyotis hirsuta Spreng. 0,589 0,023 - 0,440 0,027 - 0,438 0,085 -

14 Stemonurus coriaceus Miers 0,485 0,089 16,2 0,411 0,030 2,14 0,447 0,094 -

15 Paederia consimilis Pierre ex

Pitard 0,518 0,011 10,5 0,451 0,051 - 0,394 0,096 9,63

16 Elsholtzia penduliflora W.W.

Smith 0,544 0,022 6,04 0,438 0,018 - 0,398 0,098 8,71

17 Phyllanthus chamaepeuce Ridl. 0,563 0,021 2,76 0,428 0,024 - 0,43 0,083 1,37

18 Stemona tuberosa Lour. 0,533 0,054 7,94 0,409 0,016 2,62 0,422 0,085 3,21

19 Solanum diphyllum L. 0,543 0,023 6,21 0,424 0,023 - 0,462 0,089 -

20 Sp 0,544 0,002 6,03 0,412 0,022 1,90 0,445 0,079 -

21 Glochidion eriocarpum Champ. 0,493 0,027 14,8 0,414 0,032 1,43 0,405 0,081 7,11

47

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

22 CCTT 0,556 0,029 3,97 0,414 0,060 1,43 0,454 0,096 -

23 Wrightia dubia Spreng. 0,512 0,031 11,6 0,421 0,029 - 0,435 0,056 0,229

24 Mosla dianthera Maxim. 0,556 0,029 3,97 0,421 0,015 - 0,434 0,08 0,458

25 Cardiospermum halicacabum L. 0,563 0,016 2,76 0,393 0,023 6,43 0,453 0,083 -

26 Stemonurus coriaceus Miers 0,558 0,014 3,62 0,390 0,024 7,14 0,444 0,074 -

27 Dracaena gracilis Wall. ex

Hook.f. 0,529 0,041 3,86 0,462 0,033 - 0,468 0,088 -

28 Clerodendrum cyrtophyllum Tucz 0,591 0.036 - 0,393 0,063 7,14 0,468 0,058 -

29 Uncaria cordata Lour. Merr. 0,612 0,002 - 0,411 0,031 2,14 0,492 0,079 -

30 Smilax poilanei Gagnep. 0,503 0,052* 13,1 0,404 0,022 3,81 0,448 0,071 -

31 Illigera parviflora Dunn 0,608 0,031 - 0,411 0,025 2,14 0,464 0,074 -

32 Lygodium scandens 0,589 0,086* - 0,417 0,027 0,714 0,465 0,067 -

33 Melastoma sanguineum Sims 0,549 0,058* 5,18 0,450 0,031 - 0,425 0,071 2,52

48

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

34 Smilax corbularia Kunth 0,458 0,168 20,9 0,403 0,274 4,04 0,436 0,076 0

35 Streptocaulon juventas Lour.

Merr. 0,521 0,038 10,0 0,411 0,034 2,14 0,463 0,068 -

36 Ardisia gigantifolia Stapf 0,564 0,020 2,60 0,440 0,032 - 0,424 0,057 2,75

37 Pseuderanthemum bracteatum 0,546 0,002 5,70 0,407 0,030 3,09 0,455 0,075 -

38 Mussaenda cambodiana Pierre ex

Pitard 0,517 0,026 10,7 0,444 0,019 - 0,452 0,084 -

39 Hedyotis hedyotidea DC. Merr. 0,559 0,038 3,45 0,442 0,036 - 0,454 0,064 -

40 Psychotria rubra Poir. 0,605 0,006 - 0,468 0,038 - 0,48 0,068 -

41 Mussaenda densiflora Li 0,602 0,036* - 0,467 0,021 - 0,465 0,074 -

42 Smilax perfoliata Lour. 0,476 0,002* 19,3 0,383 0,018 8,81 0,46 0,093 -

43 Premna fulva Craib 0,557 0,012 3,79 0,442 0,022 - 0,47 0,059 -

44 Selaginella uncinata Desv.Spring 0,582 0,038 - 0,353 0,013 15,9 0,465 0,082 -

49

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

45 Hedyotis ovata Thwaites ex

Hook.f. 0,503 0,020 13,1 0,410 0,014 2,38 0,435 0,088 0,229

46 Dichroa febrifuga Lour. 0,548 0,036 5,35 0,421 0,017 - 0,451 0,071 -

47 Leptonichia acuminatus Mast. 0,475 0,101 17,9 0,390 0,021 7,14 0,433 0,073 0,688

48 Melastoma saigonense Merr. 0,413 0,155 28,7 0,416 0,030 0,952 0,436 0,076 -

49 Dianella ensifolia (L.) DC. 0,506 0,037 12,6 0,401 0,034 4,52 0,416 0,084 4,58

50 Smilax bracteata Presl 0,530 0,015 8,46 0,403 0,011 4,04 0,407 0,064 6,65

51 Anoectochilus roxburghii (Wall.) 0,492 0,027 15,0 0,371 0,027* 11,6 0,431 0,089 1,14

52 Hedyotis capitellata var. mollis

T.N.Ninh 0,517 0,069 10,7 0,431 0,019 - 0,424 0,052 2,76

53 Cancora petelotii 0,519 0,021 10,3 0,406 0,308 3,33 0,452 0,071 -

54 Dipterocarpus sp. 0,528 0,009 8,80 0,421 0,017 - 0,449 0,057 -

55 Wrightia laevis Hook.f. 0,466 0,006 19,5 0,406 0,022 3,59 0,451 0,066 -

56 CCTT 0,543 0,035 6,21 0,375 0,028* 10,7 0,441 0,084 -

50

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

57 Rhynchodia pauciflora Pitard 0,548 0,082 5,35 0,440 0,013 - 0,459 0,072 -

58 Leea aequata L. 0,497 0,084 14,2 0,447 0,003 - 0,447 0,067 -

59 Cynoglossum zeylanicum 0,519 0,036 10,4 0.427 0,041 - 0,446 0,077 -

60 Chinacanthus nutans 0,466 0,176 19,5 0,472 0,022 - 0,464 0,064 -

61 Prunella vulgaris L. 0,509 0.082 12,1 0,449 0,019 - 0,45 0,063 -

62 Parashorea chinensis Wang Hsie. 0,509 0,055 12,1 0,431 0,030 - 0,461 0,077 -

63 Alangium kurzii Craib. 0,550 0,024 5,00 0,421 0,034 - 0,456 0,081 -

64 Piper bavinum C.DC. 0,500 0,012 13,6 0,419 0,020 0,23 0,439 0,064 -

65 Isotoma longiflora 0,567 0,057 2,07 0,381 0,126 9,28 0,469 0,074 -

66 Antidesma montanum Bl. 0,532 0,073 8,12 0,453 0,030 - 0,43 0,086 1,37

67 Viburnum lutescens Bl. 0,481 0,034 16,9 0,437 0,018 - 0,446 0,092 -

68 Hydnocarpus kurzii Warb. 0,547 0,071 5,52 0,404 0,037 3,81 0,462 0,071 -

69 Solanum torvum Swartz. 0,508 0,153 12,3 0,434 0,020 - 0,436 0,064 -

51

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

70 Sambucus javanica Reinw. Ex

Blume 0,535 0,069 7,60 0,488 0,060 - 0,453 0,058 -

71 Crotalaria assamica Benth 0,593 0,055 - 0,439 0,035 - 0,454 0,068 -

72 Desmodium sequax Wall. 0,539 0,025 6,91 0,439 0,038 - 0,423 0,078 2,98

73 Afzelia xylocarpa Craib. 0,526 0,053 9,15 0,449 0,031 - 0,465 0,077 -

74 Callicarpa heterotricha Merr. 0,585 0,17 - 0,458 0,029 - 0,481 0,25 -

75 Miliusa balansae Fin. & Gagnep. 0,517 0,039 10,7 0,394 0,013 6,19 0,423 0,061 2,98

76 Knema globularia Warb. 0,554 0,081 4,31 0,372 0,010* 11,4 0,43 0,063 1,38

77 CCTT 0,557 0,025 3,79 0,408 0,019 2,85 0,439 0,073 -

78 Helicteres hirsuta Lour. 0,568 0,008 1.90 0,458 0,017 - 0,443 0,074 -

79 Hypericum uralum Thumb. 0,534 0,020 7,77 0,406 0,015 3,33 0,461 0,076 -

80 Callicarpa rubella 0,558 0,060 3,63 0,426 0,024 - 0,44 0,073 -

81 Derris pachyloba 0,529 0,037 8,63 0,405 0,028 3,57 0,456 0,074 -

52

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

82 Cornus oligophlebia Merr. 0,547 0,012 5,52 0,453 0,053 - 0,438 0,065 -

83 Sterculia lanceolata Cav. 0,557 0,041 3,79 0,394 0,014 6,19 0,444 0,079 -

84 Uncaria scandens (Smith) Hutch. 0,528 0,038 8,80 0,445 0,022 - 0,474 0,083 -

85 Sabia parviflora Wall.ex Rox 0,524 0,030 9,49 0,462 0,028 - 0,455 0,071 -

86 Piper sp 0,636 0,024 - 0,562 0,026* - 0,518 0,061 -

87 Itoa orientalis 0,603 0,035 - 0,469 0,009 - 0,5 0,071 -

88 Sambucus javanica Reinw. 0,555 0,055 6,92 0,471 0,028 - 0,46 0,051 -

89 Toddalia asiatica (L.) Lamk. 0,575 0,019 0,691 0,450 0,025 - 0,479 0,074 -

90 Uncaria macrophylla Wall. ex

Roxb. 0,547 0,029 5,52 0,437 0,023 - 0,461 0,077 -

91 Oroxylum indicum 0,521 0,025 10,0 0,389 0,016 7,38 0,434 0,058 0,458

92 Crotalaria assamica

Benth 0,567 0,038 2,07 0,433 0,045 - 0,451 0,053 -

93 Kibatalia macrophylla Woodson 0,504 0,031* 12,9 0,361 0,058* 14,04 0,429 0,078 1,60

53

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

94 Epimedium macranthun Mooren

et Decne. 0,542 0,027 6,39 0,422 0,034 - 0,44 0,068 -

95 Rhabdosia sp. 0,492 0,047 15,0 0,404 0,023 3,81 0,424 0,061 2,75

96 Hypericum patulum Ham. Ex.

D.Don 0,441 0,099 23,8 0,347 0,031* 17,4 0,39 0,055 10,5

97 Mallotus apelta Muell.-Arg. 0,555 0,049 4,14 0,356 0,031* 15,2 0,37 0,066 15,1

98 Microdesmis casearifolia Planch.

ex Hook 0,494 0,038 14,7 0,382 0,022 9,04 0,418 0,086 4,13

99 Eleaocarpus nitidus Jack 0,525 0,089 9,32 0,404 0,034 3,81 0,441 0,057 -

100 Zanthoxylum avicennae DC. 0,482 0,089 16,75 0,407 0,022 3,09 0,42 0,071 3,67

101 Sapium sebiferum Roxb. 0,480 0,014 17,1 0,371 0,007* 11,6 0,388 0,061 11,0

102 Costus speciosus (Koenig) Sm. 0,510 0,031 11,9 0,408 0,017 2,86 0,444 0,07 -

103 Ficus heterophyllus L 0,541 0,036* 11,2 0,396 0,038 5,70 0,399 0,121 8,48

104 Cratoxylum pruniflorum Kurz 0,534 0,019 7,77 0,373 0,020 11,2 0,422 0,048 3,21

54

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

105 Ficus nervosa 0,554 0,021 4,31 0,421 0,043 - 0,463 0,054 -

106 Knema elegans Warb. 0,557 0,013 3,79 0,442 0,049 - 0,431 0,064 1,15

107 Leea rubra Blunne 0,496 0,039 14,3 0,389 0,029 7,38 0,451 0,064 -

108 Antidesma ambigumPax & Hoffm 0,354 0,043* 38,8 0,326 0,046* 22,4 0,389 0,06 10,7

109 Osmanthus pedulculatus Gagnep. 0,539 0,032 6,90 0,393 0,032 6,43 0,434 0,064 -

110 sp1 0,555 0,065 4,14 0,388 0,017 7,61 0,425 0,054 2,52

111 Caryodaphnosis tonkinensis

Airy-Shaw 0,472 0,051* 18,5 0,358 0,040* 14,7 0,429 0,073 1,60

112 Microdesmis casearifolia Planch.

ex Hook 0,499 0,061 13,8 0,395 0,030 5,95 0,451 0,08 -

113 Antidesma ghaesembilla Gaertn 0,522 0,030 9,84 0,394 0,053 6,19 0,416 0,05 4,58

114 Choerospondias axillaris Burtt.

& Hill 0,548 0,014 5,35 0,428 0,015 - 0,457 0,07 -

115 Aidia oxyodontaYamazaki 0,478 0,017 17,4 0,368 0,019* 12,4 0,438 0,061 -

55

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

116 Homalomena occulta (Lour)

schott 0,505 0,043 12,8 0,384 0,017 8,57 0,433 0,047 0,688

117 Cinnamomum camphora 0,562 0,008 2,93 0,409 0,017 2,62 0,436 0,072 -

118 Smilax riparia A.DC. 0,477 0,081 17,6 0,385 0,031 8,33 0,426 0,071 2,29

119 Pseuderanthemum palatiferum

(Nees) Radlk 0,509 0,028 12,1 0,445 0,023 - 0,455 0,063 -

120 Morinda officinalis How 0,561 0,021 3,11 0,449 0,043 - 0,461 0,06 -

121 Centipeda minima (L) A.Br.et

Aschers 0,503 0,008 14,1 0,422 0,029 - 0,48 0,064 -

122 Balanophora sp 0,557 0,055 13,1 0,382 0,017 9,05 0,451 0,055 -

123 Coptis teeta wall 0,487 0,031 15,9 0,391 0,032 6,90 0,447 0,068 -

124 Balanophora sp 0,539 0,011* 6,91 0,417 0,036 0,714 0,444 0,059 -

125 Hex godajam Colebr. ex. Well. 0,532 0,017 8,12 0,406 0,045 3,33 0,425 0,052 2,52

126 Oximum basilicum L. 0,577 0,019* 0,34 0,455 0,026 - 0,455 0,064 -

56

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

127 Hex godajam Colebr. ex. Well. 0,539 0,041* 6,91 0,390 0,052 7,14 0,464 0,074 -

128 Ehretia Acuminata 0,525 0,041 9,32 0,354 0,019 15,7 0,419 0,057 3,90

129 Musra barjoo sieb. 0,515 0,046 11,0 0,382 0,041 9,04 0,444 0,059 -

130 Tadehagi Triquetrum L 0,561 0,018 3,11 0,434 0,023 - 0,44 0,063 -

131 Ardisia silvestris 0.483 0,021 16,6 0,412 0,049 1,90 0,446 0,062 -

132 Bridelia balansae 0,647 0,052* - 0,465 0,035 - 0,465 0,059 -

133 Houltuynia cordata Thumb 0,545 0,064* 5,87 0,419 0,016 0,238 0,476 0,072 -

134 Clausena excavata Burm.f. 0,564 0,035 2,59 0,391 0,024 6,90 0,466 0,083 -

135 Ixora spp. 0,536 0,015 7,42 0,434 0,028 - 0,468 0,072 -

136 Stephania dielsiana Y.C.Wu 0,537 0,026 7,25 0,429 0,024 - 0,449 0,074 -

137 Salacia cochinchinensis 0,423 0,039* 26,9 0,420 0,064 - 0,425 0,041 2,52

138 Ammania baccifera L. 0,525 0,002 9,32 0,416 0,065 0,952 0,443 0,046 -

139 Cassytha filiformis L. 0,532 0,031 8,12 0,398 0,018 5,24 0,408 0,06 6,42

57

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

140 Ficus heterophyllus L 0,540 0,007 6,73 0,418 0,018 0,476 0,443 0,048 -

141 Passiflora foetida L. 0,550 0,032 5,00 0,433 0,023 - 0,425 0,048 2,52

142 Eurya ciliata Merr L 0,530 0,031 8,46 0,376 0,045 10,5 0,387 0,051 11,23

143 Ventilago leiocarpa Benth. 0,512 0,073 11,57 0,353 0,015 15,9 0,383 0,075 12,15

144 Abutilon indicum L sweet 0,571 0,136 1,38 0,429 0,023 - 0,424 0,053 2,75

145 Flueggea virosa Roxbex willd

Voigt 0,539 0,046 6,91 0,384 0,031 8,57 0,437 0,048 -

146 CCTT 0,552 0,051* 4,66 0,401 0,018 4,50 0,423 0,071 2,98

147 Glycosmis pentaphylla Correa 0,523 0,037 9,67 0,392 0,036 6,66 0,389 0,064 10,8

148 Strobilanthes cystolithigera

Lindau 0,539 0,024 6,91 0,407 0,024 3,09 0,438 0,075 -

149 Homonoia riparia Lour. 0,575 0,023 0,691 0,398 0,006 5,24 0,449 0,044 -

150 Cyclea fansipanensis Gagnep 0,574 0,006* 0,863 0,429 0,038 - 0,359 0,176 17,6

58

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

151 Costus speciosus Koenig Sm. 0,545 0,005 5,87 0,405 0,013 3,57 0,462 0,086 -

152 Curculigo orchioides Gaertr 0,515 0,027 11,0 0,413 0,033 4,86 0,454 0,047 -

153 Kaempferia galanga. L 0,497 0,063 14,2 0,425 0,041 1,67 0,413 0,059 5,27

154 Ehretia acuminata 0,518 0,048 10,5 0,417 0,038 0,714 0,41 0,1 5,96

155 Desmodium rodgeri Schindl.

Ohashi 0,528 0,015 8,80 0,382 0,026 9,04 0,431 0,092 1,14

156 Rubus leucanthus Hance 0,527 0,014 10,0 0,390 0,048 7,14 0,427 0,063 2,06

157 Boehmeria nivea L. Gaud. 0,584 0,009* - 0,443 0,013 - 0,437 0,058 -

158 Scheffena octophylla Lour 0,564 0,018 2,59 0,445 0,042 - 0,448 0,071 -

159 Sarcandra glabra Thunb. Nakai 0,540 0,028 6,73 0,414 0,044 1,43 0,414 0,087 5,04

160 Rubus cochinchinensis Tratt. 0,557 0,021 3,79 0,429 0,024 - 0,455 0,051 -

161 Pothos scandens L. 0,556 0,002 5,04 0,382 0,098 9,04 0,437 0,097 -

162 Ehretia asperrula Zoll & Mor 0,485 0,018 16,2 0,413 0,059 1,67 0,453 0,068 -

163 Stephania longa Lour. 0,564 0,018 2,59 0,382 0,033 9,04 0,451 0,052 -

59

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

164 Rourea minor Gaertn Leenh. 0,542 0,022 6,39 0,411 0,062 2,14 0,435 0,075 0,229

165 Kadsura heteroclita Roxb.

Craib 0,455 0,009 21,4 0,388 0,064 7,61 0,443 0,033 -

166 Limacia scandes Lour. 0,569 0,012 1,72 0,417 0,042 0,714 0,47 0,07 -

167 Ardisia silvestris Pitard 0,542 0,006 6,39 0,404 0,040 3,81 0,471 0,054 -

168 Rauvolfia verticilata Lour. Bail 0,555 0,017 4,14 0,430 0,043 - 0,454 0,065 -

169 Mussaenda cambodiana Pierre ex

Pitard 0,524 0,005 9,49 0,376 0,052 10,47 0,457 0,061 -

170 Homalomena occulta Lour

schott 0,555 0,019 4,14 0,415 0,087 1,19 0,449 0,057 -

171 Mucuna pruriens L. DC. 0,543 0,016 6,21 0,450 0.029 - 0,411 0,03 5,73

172 Solanum erianthum D.Don 0,555 0,011 4,14 0,398 0,041 5,23 0,456 0,059 -

173 Asarum balansae Franch. 0,440 0,006* 24,0 0,400 0,035 4,76 0,451 0,059 -

60

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

174 Erythropalum scandens Blume 0,494 0,036 14,6 0,419 0,043 0,238 0,428 0,067 1,83

175 Curculigo latifolia Dryand. ex

Ait. 0,509 0,038 12,1 0,455 0,027 - 0,453 0,069 -

176 Ophiopogon reptans Hook 0,514 0,011 11,2 0,455 0,056 - 0,434 0,058 0,458

177 Anisomeles indica

L Kuntze 0,533 0,039 7,94 0,467 0,033 - 0,457 0,062 -

178 Ardisia gracillima 0,565 0,052 2,42 0,455 0,027 - 0,466 0,075 -

179 Zanthoxylum avicennae DC. 0,575 0,045 0,691 0,455 0,056 - 0,473 0,071 -

180 Amalocalyse miceolobus

Pierre ex Spire 0,571 0,047 1,38 0,467 0,033 - 0,45 0,054 -

181 Paramygnya petebotii Guill. 0,563 0,032 2,76 0,473 0,026 - 0,494 0,085 -

182 Chloranthus japonicusSieb 0,539 0,013 6,91 0,459 0,022 - 0,456 0,052 -

183 Equisetum diffusum D.Don 0,547 0,025 5,52 0,442 0,038 - 0,429 0,066 1,60

184 Ilex glomerata King 0,547 0,036 5,52 0,439 0,034 - 0,452 0,09 -

61

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

185 Pseuderanthemum palatiferum

Nees Radlk. 0,512 0,043 11,6 0,424 0,054 - 0,434 0,052 0,458

186 Iodes cirrhosa Turcz. 0,482 0,046 16,7 0,389 0,038 7,38 0,426 0,086 2,29

187 Strobilanthes

mucronatoproductus Lindau 0,515 0,025 11,0 0,403 0,025 4,04 0,407 0,061 6,65

188 Clerodendrum paniculatum L. 0,511 0,056 11,7 0,389 0,046 7,38 0,42 0,063 3,66

189 Belamcanda chinensis L. DC. 0,423 0,167 26,9 0,348 0,036* 17,1 0,377 0,04* 13,5

190 Lygodium flexuosum L. Sw. 0,204 0,032* 64,8 0,254 0,031* 39,5 0,333

0,108* 23,6

191 Pandanus tinctorius 0,576 0,061 0,52 0,435 0,027 - 0,429 0,079 1,60

192 Euodia lepta 0,525 0,041 9,32 0,434 0,045 - 0,426 0,064 2,29

193 Tabernaemontana buffalina 0,517 0,028 10,7 0,380 0,042 9,52 0,42 0,035 3,67

194 Euphorbia hirta L. 0,548 0,034 5,35 0,433 0,021 - 0,444 0,057 -

195 Carallia brachiata 0,483 0,112 16,6 0,423 0,031 - 0,454 0,069 -

62

STT Tn khoa hc

% c ch XO


OD I% OD I% OD I%

196 Helicteres angustifolia 0,528 0,052 8,88 0,470 0,016 - 0,41 0,073 5,96

197 Tinospora sinensis 0,563 0,040 2,76 0,449 0,043 - 0,44 0,057 -

198 Genianthus laurifolius 0,531 0,038 8,29 0,440 0,036 - 0,457 0,07 -

199 Strobilanthes apricus 0,521 0,016 10,0 0,428 0,028 - 0,419 0,054 3,89

200 Alseodaphne sp. 0,527 0,042 8,98 0,456 0,046 - 0,451 0,049 -

201 Acronychia pedunculata 0,498 0,012 14,0 0,422 0,037 - 0,424 0,054 2,75

202 Actinodaphne pilosa Merr. 0,537 0,059 7,25 0,425 0,019 - 0,417 0,074 4,35

Mu chng 0,579 0,014 0,420 0,018 0,436 0,07

*, p < 0,05 khi so snh vi mu chng.

63

3.1.3. Xc nh IC50 ca cc dc liu tim nng c ch XO

5 mu th t 5 dc liu c tc dng c ch XO mnh nht ti nng 100

g/ml l : Antidesma ambigum, Caryodaphnosis tonkinensis, Asarum balansae

Salacia cochinchinensis v Lygodium flexuosum c thit lp dy nng kho

st v tin hnh xc nh IC50.

Allopurinol - mt thuc c ch mnh XO, c tc dng lm h acid uric huyt

thanh trong lm sng c s dng lm cht i chiu trong th nghim.

Kt qu c trnh by bng 3.5.

Bng 3.3. IC50 ca cc dc liu tim nng c ch XO

Mu th c ch hot XO

IC50 ( g/ml)

108. Antidesma ambigum 105,3 (53,4 - 180,8)

111. Microdesmis casearifolia 311,8 (239,1 - 399,3)

137. Salacia cochinchinensis 295,4 (191,9 - 396,1)

173. Asarum balansae 508,9 (420,7 - 703,3)

190. Lygodium flexuosum 83,6 (47,2 - 129,6)

Allopurinol 0,456 (0,416 0,497)

Nhn xt:

Lygodium flexuosum l cy c kh nng c ch XO mnh nht trong s 5 cy

thuc chn, c xc nh IC50 = 83,6 (47,2 - 129,6) g/ml.

3.2. Bn lun

3.2.1. V thng tin ca cc cy thuc a vo nghin cu

Trong 187 cy thuc c a vo nghin cu, 111 cy thuc c s dng

ph bin trong dn gian Vit Nam. Trn th gii, cng c nhiu nghin cu c th

v tc dng, thnh phn ho hc v cc hot tnh sinh hc ca chng. Th d cc cy

thuc nh thin nin kin (Homalomera occulta), dm dng hoc (Epimedium

macranthun), long no (Cinnamomum camphora) c s dng nhiu trong dn

gian cha cc bnh vim khp, au gn ct ...[10] v trn th gii cc cy ny

64

cng cng c nghin cu nhiu v tc dng chng vim, chng oxy ho. Bn

cnh , 76 cy thuc nh v hng giai (Stemonurus coriaceus Miers), bng bong

(Lygodium scandens), mua lng (Melastoma saigonense), cm lng (Eleaocarpus

nitidus) ... mi ch c s dng trong dn gian Vit Nam, trn th gii cha c cc

nghin cu v tc dng ca cc cy thuc ny.

Mt s cy thuc nh thng sn (Dichroa febrifuga Lour), bm bc

campuchia (Mussaenda cambodiana), mua b (Melastoma sanguineum), ... cha c

cc nghin cu v tc dng ca b phn dng nh trong cc mu c sng lc.

Ngoi ra, mt s mu cng loi nhng c thu hi cc vng khc nhau (ph lc

1) v mt s mu cng loi nhng khc b phn dng (ph lc 2) c a vo

sng lc so snh kh nng c ch XO gia cc mu , t tm ra mu c tc

dng c ch XO tt hn.

3.2.2. V kt qu sng lc tc dng c ch XO in vitro trn a Costar 96 ging

Trong giai on sng lc, tm ra cc cy thuc c kh nng iu tr gt,

nghin cu sng lc in vitro nh gi tc dng c ch XO ca cc cy thuc thng

c ngh n u tin v nghin cu ny hon ton c th trin khai c v n

kh hp l vi iu kin nghin cu trong nc. Tc gi Nguyn Th Thanh Mai v

cng s thc hin cng trnh nghin cu ca mnh vi cc dc liu c thu hi

cc tnh pha Nam [86]. Trong khi , khu vc min Trung v min Bc cha c

nghin cu sng lc no. V vy, ti "Sng lc cc cy thuc c tim nng iu

tr bnh gt thng qua c ch XO in vitro" l cng trnh nghin cu u tin c

tin hnh vi cc cy thuc c thu hi ti cc tnh min Trung v min Bc.

sng lc tc dng c ch XO ca dc liu, kho lun tin hnh th

nghim in vitro trn a 96 ging theo phng php ca Noro [93] v c sa i

ph hp vi iu kin phng th nghim. i vi cc dch chit dc liu, cc tc

gi thng thc hin nghin cu in vitro vi ba nng ca mu th l 100 g/ml,

50 g/ml v 10 g/ml [121], [86]. sng lc 202 mu dc liu trong nghin cu

ny, kho lun cng p dng 3 mc nng 100 g/ml, 50 g/ml v 10 g/ml cho

tt c mu th nh gi nh hng ca dch chit ln hot XO in vitro. Qu

65

trnh sng lc c lm trn a 96 ging nn c th tin hnh vi nhiu nng ,

lp li th nghim vi nhiu a trong khong thi gian ngn v c th tin hnh

php o nhanh chng, lin tip, t ng. Tuy nhin, a Costar 96 ging s dng

lm thc nghim thng c dng o vi bc sng ln hn 340nm. Khi p

dng trong nghin cu ny, bc sng s dng l 290nm, do sai s mc phi kh

ln.

Trong 202 mu dc liu c sng lc, ti nng 100 g/ml c 20 mu

c tc dng c ch XO, 13 mu c tc dng c ch XO nng 50 g/ml v c 3

mu c tc dng c XO nng 10 g/ml. Bn cnh , cc dc liu c tc

dng c ch XO khng tp trung m phn b ri rc cc h khc nhau. Nh vy,

so vi cc nghin cu sng lc khc, t l cc cy thuc c tc dng c ch XO

khng cao v cc nghin cu trc tp trung sng lc cc dc liu c s dng

theo kinh nghim dn gian hoc theo y hc c truyn vi tc dng chng vim,

chng oxy ho. Trong khi , cc dc liu c sng lc trong ti ny l nhng

cy thuc thuc d n "Bo tn ngun cy thuc c truyn", trong dn gian v y

hc c truyn khng ch c cc cy thuc c dng vi tc dng chng vim,

chng oxy ho m cn c nhiu cy thuc c dng vi cc tc dng khc nh

chng ung th, an thn, h huyt p ...

3.2.3. V kh nng c ch XO ca cy thuc tim nng

Kho lun tin hnh xc nh IC50 trn 5 mu th c kh nng c ch XO

mnh nht nng 100 g/ml l: Antidesma ambigum, Microdesmis casearifolia,

Salacia cochinchinensis, Asarum balansae v Lygodium flexuosum.

Antidesma ambigum v Asarum balansae hin cha c bo co v thnh

phn ho hc, hot tnh sinh hc. Tuy nhin trong chi Antidesma c cy Antidesma

madagascariense v Antidesma thwaitesianum c nghin cc c kh nng

chng oxy ho [78], [101] v trong chi Asarum c cy Asarum sieboldii c

nghin cu v tc dng chng vim vi nhiu hot cht c phn lp [102].

Vi IC50 > 500 g/ml, Asarum balansae l cy c tc dng c ch XO yu

nht trong 5 cy, yu hn rt nhiu so vi allopurinol. Antidesma ambigum l cy

66

c kh nng c ch XO mnh th 2 vi IC50 = 105,3 g/ml (53,4 - 180,8). Mc d

cha c bo co khoa hc no v Antidesma ambigum nhng cc hp cht

polyphenolic c bo co cng hot ng chng oxy ho trong chi Antidesma

l cy Antidesma thwaitesianum [101]. Nh vy hot ng c ch XO ca

Antidesma ambigum cng c th do s hin din ca cc thnh phn phenolic tng

t nh cc cy khc trong chi.

Microdesmis casearifolia cha thy c bo co v thnh phn ho hc cng

nh cc tc dng ca n. Cy Salacia cochinchinensis mi ch c cc bo co v tc

dng h ng huyt [8].

Dch chit methanol ca Lygodium flexuosum c kh nng c ch XO mnh

nht trong 5 dch chit t 5 cy c tim nng iu tr gt c xc nh IC50 vi

IC50 = 83,6 g/ml, tuy nhin vn thp hn nhiu so vi allopurinol vi IC50 = 0,456

g/ml c th v dch chit c dng trong nghin cu l dch chit ca c cy,

khng phi cht tinh khit nn kh nng c ch km hn nhiu so vi allopurinol.

Lygodium flexuosum l cy thuc kh ni bt vi nhiu nghin cu v tc dng

chng vim, chng oxy ho [33]. Trong mt nghin cu v cc thuc s dng trong

dn gian ca n , r ca cy Lygodium flexuosum c dng iu tr thp

khp v cc bnh vim nhim [108]. Kh nng chng oxy ho ca cy thuc ny

c nghin cu rng ri nht vi cc hp cht phenolic c phn lp. Bn

cnh cc phn on methanol cng cho thy s hin din ca quercetin-1

flavonoid in hnh c ch XO [56]. Nh vy, kh nng c ch XO ca Lygodium

flexuosum c th do cc phenolic v quercetin c mt trong thnh phn dch chit

methanol ca cy.

Qu trnh sng lc cc dc liu c kh nng c ch XO pht hin ra

Lygodium flexuosum - cy thuc c tim nng nht. cng l c s nghin cu

su hn v tc dng dc l cng nh cc thnh phn ho hc ca Lygodium

flexuosum, t c th ng dng trong iu tr.

67

KT LUN

1. Kt lun

Trong khun kh ti: Sng lc cc cy thuc c tim nng iu tr bnh

gt thng qua c ch XO in vitro, kho lun thu c nhng kt qu sau:

1. thu thp c c bn thng tin khoa hc ca 202 mu cy thuc, thuc

74 h a vo nghin cu.

2. Trong s 202 dch chit methanol t 187 loi:

- Ti nng 100g/ml c 20 mu c tc dng c ch XO, ch c 1 mu c tc

dng c ch > 50%.

- Ti nng 50g/ml c 13 mu c tc dng c ch XO, khng c mu no

c tc dng c ch > 50%.

- Ti nng 10g/ml c 3 mu c tc dng c ch XO, khng c mu no c

tc dng c ch >50%

3. xc nh c IC50 ca 5 dc liu tim nng nht. Dch chit

methanol ca Lygodium flexuosum c IC50 = 83,6 (47,2 - 129,6) g/ml th hin kh

nng c ch XO mnh nht trong cc mu nghin cu.

2. xut

Vi nghin cu in vitro trn a 96 ging, kho lun mi ch c th sng lc

v xc nh IC50 ca cc cy thuc c tim nng c ch XO. Do cn c nhng

nghin cu dc l thc nghim tip theo khng nh tc dng ca cc cy thuc

ny. Kho lun xin a ra hai xut trin khai nghin cu tip nh sau:

- M rng thm i tng dc liu a vo sng lc.

- nh gi tc dng h acid uric huyt thanh ca cy Lygodium flexuosum

in vivo nh hng cho nghin cu su tip theo v dc liu ny.

TI LIU THAM KHO

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