Tgp cMDu-grc lifu, iSp 19, sd 2/2014 (Trang 235

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Tgp cMDu-grc lifu, iSp 19, sd 2/2014 (Trang 235 -240)

NGHIEN Ciru DOC TINH CAP VA BAN TRlTonVG DIEN CUA HO^iT CHAT CHONG OXY H 6 A POLYPHENOL CHIET TlT RONG NAU

Vd Mai Nhie Hiiu'', Bdi Minh Ly', Tran Thj Thanh Van',

^ Phgm Quoc Long', Vu Manh HUn^

Vi?n Nghien cuu vd &ng ditng Cong ngh? Nha Trang, Vi?n Hdn ldm KH vd CN Vi$t Nam:

Vi4n hda hgc cdc hgp chdt thien nhien, Vien Hdn ldm KHvd CH Viet Nam;

^Hoc Vi$n Qudn Y

*Email: nhuhieu(a!nitra.vast.vn (Nhan hh\ ngdy 15 thdng 6 nSm 2014)

T6m tat

Rong nau chiia. mpt s6 loai h(;<p chat c6 lijri siic khoe con ngudi, bao gfim carbonhydrat-nhQng hgp chit gpi 1^

polysaccharid, carotenoid \h polyphenol-nhihig hpp chat dupe ggi la phlorotannin. la ho^t chit chii ylu 6 rong nau. Nh&ng polyphenol n^y c6 kha nang qu^t cac gdc ty do la nguyen nhan gay ra cac benh hifim ngheo. Trong nghien cuu nay, chiing toi tien hinh thii nghi?m dpc tinh cap va bin trudng diln dS d4nh gia dO an toan cua nguyen lieu polyphenol tir rong nSu. Ket qua nghien cilu cho thiy: che phim polyphenol kh6ng l\ik, hi^n dOc tinh cip trfin chupt nhat trSng dftng Swiss iruong thinh theo duimg uong vdi mCrc lieu cao nhat theo ducmg sonde d^ day Ii 10g/kg/72gi6 ( LDso >10g/kg/72gi6). Ket qua khao sit tren dpc tinh bSn truimg diln cho thiy ch^ phdm khong lam anh hitong toi s^^ phat tri^n trpng lupng co the tho thi nghiem, khflng lam biln dfli di§n tim tho, va ciic chi s6 huylt hpc (nhu h6ng ciu, bach cau, tilu ciu \k ham lupng hemoglobin) sau khi cho uong vdi Hfiu 0,5g/kg dimg Uong 42 ngiy. Cac chi s6 dinh gii chiic nSng gan (hoat dp AST. ALT), thiin (nfing d$ ure.

creatinin) trong gidl hgn binh thufmg,

T£r kh6a: Polyphenol. DQC tinh cdp. DQC linh bdn trudng diin. Rong ndu Summary

Study on the Acute and Subchronic Toxicity of Polyphenol Antioxidant Substance Extracted from Brown Seaweed Brown seaweed may contain several types of compounds with potential health benefits, including carbonhydrate-like compounds called polysaccharides, carotenoids and polyphenol-like compounds called phlorotannnins. These polyphenols have scavenging activity on free radicals. In this study, the acute and subchronic toxicity of polyphenol have been studied to evaluate its safety. The results showed that brown seaweed polyphenol up to the highest dosage of lOg/Tcg body weight did not induce any acute oral toxicity on rats aHcr 72 hrs of observation. Subchronic toxicity study in rabbits revealed that brown seaweed polyphenol orally administered at dose of 0.5 g/kg daily for 42 days did not change the body weight and electrocardiogram as compared to control. Hematological indices (red blood cell, white blood cell, platelet and hemoglobin content), hepatic indices (AST, ALT activity) and renal indices (urea, creatinin levels) of rabbits after brown seaweed polyphenol treatment were in normal biological values.

Keywords: Polyphenol, Acute toxicity. Subclironic toxicity. Brown seaweed.

1. fiat van de (BEL-7402) vd te bao bach cau murine (P388) Polyphenol thien nhien chiet xudt ttr rong ndu [8]. Nhdm tao co sd cho viec phat trien theo djnh cd nhieu tac dyng sinh hpc gia trj nhu chdng oxy hudng thanh thudc, trong bdi bdo nay, che phdm hda, chong dj ung, chong ung thu, khang vi rut polyphenol chiet ti> rong nau dupc nghien cuu HIV, chong khoi u...[3]. Ngoai ra polyphenol dpc tinh cdp va ban trudng diln tren thyrc nghi?m.

cung cd hoEit tinh chong vi sinh v^t va cdm lanh 2. Doi tuong va phutmg phap nghien cuu [4], ho trp dieu trj cdc b?nh ve tieu dudng, thdp 2.1. Mdu thuoc thir nghien cuv:

khdp, viem nhiem mgn tinh [5,6,7]. Hpp chdt Bpt polyphenol dupc chi6t xudt tii rong ndu dioxinodehydroeckol chiet xuat tir rong ndu thu^ chi Sargassum {Sargassum mcchtre, Sca-gassum Laminaria japonica chong l^i s(r phdt trien te bao polycystum) d^t tieu chuan co sd vdi ham lupng ung thu VIJ d ngudi, te bao ung thu gan d ngudi phlorotannin lir 15,0 - 20,0%, ham lupng carbohydrat

Tgp chi Dugc lieu, tap 19, so 4/2014 235

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tit 20-40 %. Tdng sd VSV hieu khi (Kl/g) < W, Conforms (K.yg)<\0\

Bpt polyphenol dat tieu chuan tinh s^ch, tan trong nudc do Vien Nghien cdu va U'ng diing Cdng nghe Nha Trang - Vien Han lam KH & CN Viet Nam cung cdp, xay d\mg theo tieu chuan cua d6 tai cdp nha nudc "Nghien cmi xay dirng quy trinh tach chiet va sang loc cac chat phlorotannin cd hoat tinh sinh hoc tir rong nau t^i viing bien Nam Trung bo" va dupc bao chi tai Bd mdn Dupc - Hpc Vi?n Quan Y thanh dang dung dich dudng uong d cdc ndng dp khdc nhau, diing cho dpng vat thi nghiem udng de nghien cuu ddc tinh cdp va nghien ciru dpc tinh bdn trudng dien.

2.2. Dong vdt thuc nghiem:

Doc tinh cap: Chupt nhat trdng ddng Swiss trudng thanh, trpng lupng 20,0 ±2,0 g, dat tieu chudn thi nghiem, do Ban ehan nudi dpng vdt thirc nghiem - Hpc vi#n Qudn Y cung cap.

Dpc tinh ban trirdng dien: Thd nha chiing Orychlolagus cuniculus trudng thdnh, trpng lupng 2,0kg - 3,Dkg, dat tieu chudn thf nghiem.

Trudc khi thi nghiem dupc theo doi 5 ngay, lira chpn thd khoe manh, nhanh nhen, Idng mupt, khdng cd b?nh ngoai da va dudng tieu hda.

Dpng vat nghien cuu dupc cung cap bdi Ban chdn nudi dpng vdt thi nghiem, Hpc vipn Qudn y va deu dupc nudi duong trong dieu kien chung cOa phong thi nghi?m dupc ly tir 5 ngay trudc khi ti6n hanh nghien ciiu: nhiet dp phdng Id 20''C, thuc dn tdng hpp, uong nudc sach, tu do.

So lupng ddng vat vd each phdn Id nghien curu dupc ghi chi ti8t tgi mdi thi nghipm.

2.3. Phucmg phdp nghien cthi

2.3.1. Phuang phap nghien ciiu dpc tinh cdp:

Phuang phdp xdc dinh dpc tinh cdp theo dudng udng dupc md ta bdi Abrham W.B. vd OECD (2002) [9,10]. Sir dung ID lo thi nghiem, mdi Id 12 con.

Chupt thi n^i^m duac udng polyphenol voi cac muc lieu tang ddn theo timg nhdm. Theo ddi ket qua d cac nhdm sau 24h, 48h vd 72 h tir thdi diem sau udng thudc.

* Tinh todn ket qua: Theo phucmg phap cua

Livschitch P.Z. cai tien (1986) [1].

Nhdm thu I, 2, 3, 4, 5, 6, 7, 8, 9, 10: udng polyphenol vdi cdc mure lilu tuang ung la : 1,0, 2,0; 3,0; 4,0; 5,0; 6,0; 7,0; 8,0; 9,0; 10,0 thi trgng chupt/72gid.

2.3.2. Phuang phdp nghien cuu ddc tinh ban trudng dien:

Dupc md ta bdi phuong phap Abrham BW.

theo quy dinh ciia Td chuc Y t l the gidi WHO [11], Td chirc hpp tdc vd phat trien kinh \k (Organisation for Economic Co-operation and Development- OECD) [10], Dupc diln Viet Nam [2]. Theo cac ddn lieu da dupc y van cdng bo va cua cdc tac gid tren the gidi: che phdm dirge dimg tren ngudi khoang 6 tuan cho I lieu trinh (mpt dpt) dieu trj la thich hop. Do vdy mdc thoi gian dupc chpn la 6 tuan.

Thd dupc chia thanh 2 Id:

- Ld chdng (12 con); udng nudc cdt, lieu uong 0,5 mL/kg khoi lupng ca the (KLCT)/hang ngay.

thdi gian 42 ngay qua dudng sonde dg day.

- Ld thtJT thudc (12 con): udng polyphenol, liSu 0,5g/kg KLCT/24h (pha trong 0,5ml nudc cai) qua dudng sonde da day.

2.4. Cdc chi tieu ddnh gid

- Chi tieu sinh ly - dupc ly: Theo doi the trang chung, hoat dpng, an udng cua thd. Kh6i lupng ca the thd.

- Chi tieu huyet hpc: So lupng hong cau, bach cdu, tieu cdu, ham lupng hemoglobin dupc djnh lupng tren may xet nghi$m huyet hpc t\r dgng cua Nhdt Ban.

- Chi tieu sinh hda: dinh lupng hogt dp enzym ALT, AST, ham lupng creatinin va ure huyet thanh. Xet nghiem tren mdy do sinh hda t(r d^ng A25 cua Tay Ban Nha.

- Chi tieu gidi phau md b^nh hpc: quan sat hinh anh dai the gan, lach, thgn vao ngdy thir 42, Sinh thiet ngdu nhien cac tgng gan, lach, th^na 1/3 sd thd thi nghiem. Tiln hdnh xCr 1^ mauiJe nghien ciju hinh thai cdu true md bpnh hpc cii>

cdc thd th\rc nghipm tai labor giai phdu bfnh-ino bpnh. Dpc ket qua qua kinh hien vi anh sang thudng. Chpp vd in anh qua kit noi vdi may « tinh bdng phdn mim chuyen dyng.

236 Tgp chi Dugc lieu, tap 19, so4/20U

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* 7*07 gian xit nghiem: D^c tinh cap: 72 gid; DOc tinh ban trudng diln: 42 ngay.

* Th&i mim xit nghi$m: lay mau xet nghi#m

eac chi s6 sinh hda, huylt hpc, ghi dipn tim tgi 3 thdi diem: xuat phat diem, sau 3 tudn, sau 6 tudn.

Thdi gian thi nghipm 42 ngdy.

* Phucmg phdp xir ly thong ke :

Cac chi tieu nghifin cuu dupc lupng hda, phdn tich, xir ly vd so sdnh thong kl. Sir dung cac chucmg trinh Microsoft excel va sir dung t-test Student va phep so sanh trudc-sau. Su khdc biet cd y nghia thdng ke khi p<0,05.

3. Ket qua va thao luan

3.1. Ket qud thu dge tinh c^ cua polyphenol

Sau 72 gid cho chupt udng thudc, quan sdt, theo ddi bilu hien vd hogt dpng nhdn thdy, khdng chupt nao chet d tat cd nhdm nghien cuu tii lieu 1,0 g/kg din 10,0 g/kg. Vdi miic lilu cao nhat 10,0 g/kg dua vdo theo dudng sonde dg day, chira thay dupc dpc tinh cdp cua polyphenol theo dudng udng d chupt nhdt trdng. Theo phan loai ddc tinh ciia GHS (Globally Harmonised System for Classification of Chemicals) nhung chdt cd gia tri dpc tinh cdp LD50 > 5000 mg/kg thi frpng dupc coi la chdt gdn nhu khdng ddc. Dilu nay cbiimg td polyphenol gdn nhu khdng ddc.

Bing 1. Kat qua dpc tinh c ^ cua polyphenol tren chu^t nhat trang theo du&ng u6ng Mi6m

1 2 3 4 5 6 7 8 9 10

S6 mSu (n)

12 12 12 12 12 12 12 12 12 12

Lieu (g/kg) 1,0 2,0 3,0 4,0 5,0 6,0 7,0 8.0 9,0 10,0

So CNT song sau 72 h

12 12 12 12 12 12 12 12 12 12

SSCNT chet sau 72 h

0 0 0 0 0 0 0 0 0 0

3.2. Dge tinh bdn trudng diin Kit qud n^ien ciru dpc tinh cap cho biet khdng cd 3.2.1. Anh hudng cua polyphenol tren s\r phdt hi$n tirpng chupt nhdt chet sau 72 h khi eho uong din trien khoi lupng co the (KLCT) thd thi nghi?m lilu l O ^ g KLCT. Vi vdy, lilu dupc chpn cho did Id khi diing dai ngay: d mtic 1/20 cCia lilu cao nhdt ndi tren (0,5^g KLCH).

B&ng 2. Anh huong ciia polyphenol doi v6i lch6i lupng co thS (KLCT) th6 ,—,,_^^ Lo nghien cihi

Thfri dilm nghiSn cihi ~ — ~ - , , ^ ^ Trii^ thi nghif m (a)

Sau 3 tuin (b) Sau 6 tuin (c)

P

Chung {n=I2) X ±SD 1,96±0,10 2,10±0,11 2,21±0,13

Polyphenol (n=72) X ±SD 2,02 ±0,12 2,13*0,12 2,24 ±0.10 p » , < 0.05,p,j,< 0.05:p^< 0.05

Pi-i

>0,05

Ket qua nghien curu d Bang 2 cho thdy, KLCT ciia thd d Id diing polyphenol vdi Id chirng sinh hpc tgi cdc thdi dilm thay sii thay ddi khdng cd y

nghTa th6ng k%ycnp> 0,05 (p ,„^p./j 'vap ^tmfi-ij

> 0,05). So sdnh giOa cac thdi diem sau vdi trudc thay KLCT thd cua 2 Id tdng, sv thay doi cd y

nghTa thong ke vdi p< 0.05 (pb-a < 0,05: Pc-b <•

0,05; pc^ < 0,05). Nhu vgy, che phdm polyphenol lieu 0,5g/kg KLCT diing ddi ngay (42 ngdy) khdng lam anh hudng tdi s\r phdt trien trpng lupng ca the thd.

3.2.2. Anh hudng ciia polyphenol doi vdi di^n

Tgp chi Dugc lieu, tdp 19, s6 412014

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tim thd thi nghiem khi diing dai ngay Kit qua Bang 3 cho thdy giua cac thai diem trudc va sau thi nghiem, cac thdng sd (tan sd, bien dp) cua dipn tim thd d cac Id thay doi khdng cd y nghTa thdng ke voi ;j > 0,05. 6 ciing mpt thdi dilm tdn so, bien dp ciia Id dung ch6 phdm polyphenol (lilu uong 0,5g/kg/ hdng ngay) so vdi

Bang 3. Anh hu6ng cua polyphenol

Id chumg thay doi khdng cd y nghTa tiidng ke vdi p > 0.05. Khdng cd sdng bat thudng tren di?n tim cua cdc Id thd tai cac thdi dilm nghien ciiru. K6t qua tren chimg td chi pham polyphenol (lieu udng 0,5g/kg KLCT) diing dai ngay (42 ngay) chua thdy cd bilu hipn gay anh hudng tdi dien tim thd nghien cCru.

16i vin di§n tim cua tho cr dao trinh Du

TSns6 (chukj' /phut)

Bien d$

s6ngR (mV)

^ ^ ^ - — _ . ^ LS nghiSn cihi Th&i diem x6t nghifm ' — ^ ^

Tru^c thi nghiem (a) Sau 3 tuin (b) Sau 6 tuan (c)

P Trin^c thi nghiem (A)

Sau 3 tuan (b) Sau 6 tuan (c)

P S6ng bit thirfmg

Chihig (n=/2) X ± S D 204,67 ± 27.12 236.00 ±24,24 220.00 ±29.75

Polyphenol (rt=/2) X ± S D 231,71 ±56,13 212,71 ±42,11 232.29 ±35.32 p«,> 0.05; p^>0.05, p^>0.05 0.592 ±0.124

0.495 ±0.132 0.503±0.131

0.596 ±0,079 0,524 ±0,098 0,529 ±0,091 p „ > 0.05: Pb.,> 0,05;p^> 0.05 Khdng 1 Khong

Pi.i

>0.05

-

3.2.3. Anh hudng cua polyphenol d6i vdi mpt sd chi tieu v l huyet hpc thd thi nghipm khi dimg dai ngay:

BAng 4. Anh hudng ciia polyphenol tdri cdc chi sd huyet hpc ciia tho thi nghiem ChitiSu

Hdng clu (Tetra/L)

Bach clu (GigaA.)

Tilu clu (Oiga/L) Hemoglobin

(Hb) P

^ ~ ~ ~ ~ ^ ^ ^ l , 5 nghiln cihi Thiri dilm ~ ^ - - ~ , . „ ^ ^

xtt nghifm ^ ^ ~ ^ , - „ ^ Tnrdc thi nghiem (a)

Sau 3 tuin (b) Sau 6 tuin (c) Trudc thi nghiem (a)

Sau 3 tuin (b) Sau 6 tuan (c) Tfirdc thi nghiem (a)

Sau 3 tuin (b) Sau 6 tuin (c)

Chung(n=72) X ± S D 5,01 ± 0,96 5,12 ±0,95 4,81 ± 0,44 5,77 ± 1,58 5,80 ±0,94 5,57 ±1,48 463.17± 175,21 471.50 ±118.30 474.00 ±184.96 112.00± 13.01 112.00 ±10.86 109.83 ± 8,64 p^.,> 0,05; p^> 0.05;p„..> 0,05

Polyphenol {n=12) X ± S D 4,69 ±0,78 5,06 ±0,51 4,90 ±0,22 5,53 ± 1,57 5,74 ±1,49 5,73 ±1,26 459.86 ±116.28 481.861112.26 479.71 ± 83.32 100.71 ±11.13 100.71 ± 12.99 110,86 ±5.70

Pu

>O.05

>0.05

>0,0S

>0,05

>0,0i

>0,0!

>o,os

>0,05

>o,os

>o.os

Ket qua Bang 4 cho thay gii^a cdc thdi diem sau va trudc thi nghipm, cac thdng sd huyet hpc nhu hdng cau, tilu cdu, bach cdu, ham lupng hemoglobin ciia thd gi&a cac Id thay ddi khdng cd y nghTa thong ke vai p> 0,05 (pc-a > 0.05:Pb-

a > 0,05: Pc-b ^ 0.05), so sanh d ciing mpt th&i dilm thay cdc thdng sd ve huylt hpc cua thd giiJa Id diing polyphenol (lilu 0,5g/kg KLCT) so vdi Id chung thay doi khdng cd y nghTa th6ng ke v d i p > 0 . 0 5 (p2.i > 0,05). Kit qua d Bang 4 cho

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Tgp chi Dugc Ueu, tap 19, s^4/2014

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thay polyphenol (lieu 0,5g/kg KLCT) diing dai cdu, tilu cau va vdn ndm trong gid tri binh ngdy (42 ngay) khong anh hudrng din co quan thudng cua thd.

tgo mau thdng qua cac chi so huylt hpc mau 3.2.3. Anh hudng cua polyphenol doi vdi chiic ngogi vi bao gom hong cau, huyet sdc td, bach nang gan, thgn ctia tiid:

Bdng 5. Anh hircmg ciia polyphenol tdi cic chi s6 sinh h6a cua tho

Chi tilu ALT (U/L)

AST (U/L)

Creatinin (nmol/L)

uic (mmol/L)

P

^^^^^ Lfl oghiSn cihi ThM dilm~'~-~^^^_^^

xkt nghifm ^ .^.^

Trirdcjhinghi$m(a) Sau 3 tuan (b) Sau 6 tuan (c) T r u ^ thi nghiem (a)

Sau 3 tuin (b) Sau 6 tuin (c) T r u ^ thi nghiem (a)

Sau 3 tuin (b) . Sau 6 tuin (c)

Chlhig (It'll) X ± S D 39,67 ±9.67 43,50 ±11.11 39,67 ±18,29 68,00 ± 12,58 79.00± 11.29 84.50 ±12.00 122.14± 11,21 106,07 ±14.60 121.00 ±14,26 5,89±1.17 5.43 ±1,42 5.48 ±0.61 p^^>0,05, p^> 0,05;p.^> 0.05

Polyphenol (/t=72) X ± S D 40,63 ± 17,50 48.00 ±14,31 40.63 ± 15,24 74.71± 11,02 83,29 ± 14,50 86.86 ±11,79 120.34 ±12.24 102.04± 12.40 115.40 ±14.07 5.63 ±0,93 5,14±1.21 5.26*0.82

Pi-i

>0,05

>0,0S

>0,OS

>0,05

>0,0S

>0,05

>0,0S

>0.0S

>0.05

>0,0S

Kit qua Bang 5 cho thay giOa cac thai diem trudc vd sau thi nghipm, cac chi so sinh hda ctia thd giiJa cdc Id thay doi khdng cd y nghTa th6ng ka vdi p > 0.05 (pca > 0.05; pb-a > 0.05:

Pc-b > 0,05). d ciing mpt thdi diem chi so sinh hda ciia thd d 16 diing polyphenol (lieu 0,5g/kg KLCT) so vdi Id chiing thay d6i khdng cd y nghia th6ng ke vdi p > 0,05 (pj.j > 0.05). Kit qud cho thay polyphenol (lilu 0,5g/kg KLCT) diing dai ngdy (42 ngay) khdng dnh hudng tdi chii:c ndng gan (thdng qua chi so vl hogt dp

enzym ALT vd AST) va chiic ndng thgn (thdng qua chi so vl ham lupng creatinin va ure huyet thanh) ctia thd.

3.2.4. Kit qud nghien cim dnh hudng cua polyphenol tren md b?nh hpc 3 tgng cCia thd.

Ket thuc dpt nghien cihi, phdu tich cac co quan gan, Idch vd thgn. Quan sdt va so sanh dgi thi thdy: mdu sde, hinh thdi cua gan, Idch va thgn d Id ditng polyphenol khdng khdc so vdi chiing.

Kit qud vl hinh dnh md bpnh hpc cdc tgng gan, lach, thgn dupc trinh bdy d Bdng 6.

Bang 6. Kit qua nghien dm ve m6 b^nh hpc cua gan, l^h \k tiijin tho Cor quan

Can

Chi tieu

Te bao gan C&itnJctiaiH^

cdu true khodng cira Mgch mdu Cdc tdn thuang

Khlu^

L6 nghiSn cihi Cbimg

binh thuimg binh thirimg binh thudng binh thudng khfing c6 Gan binh thuang

Polyphenol Binh tiiuimg. bJo tuong t h u ^ nhJt

C4c ti6u thu)- gan r5 binh thudng Tinh mach trung tSm ti6u thuy xung huy^t nh?

khong c6 Khong thay hinh dnh ton thuang

Tfp chi Duac lieu, tdp 19, so 4/2014

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U c h

Than Mdu sac

Cdu true viing tOy trdng cdc nang lympho Cdu true mgch mdu Cdu true xoang Cdc tdn thuang Kitlu^n Mdu sdc Cdu true viing vo Cdu true viing tUy Cdu than ong than Ton thuang

Kh lu$n

Naudpm Rdrdng Binh thufmg Binh thucmg Khong c6 To chuc binh thudng

Mdu nau nh^t R C r ^ g Binh thudng Binhthirdng Binh thudng Khong c6 T6 chitc than binh thudng

Nau d|im R 6 r ^ g Binh thirdng Binh thudng Khong c6 To chux: lach binh thudng

Mau nau nh?t R5 rilng R S r ^ g Binh thudng, khoang Bowmann rO

Cac dng than d€u Khong c6

To chijrc than binh thudng 1

Ket qua dpc tinh ban trudng diln vdi lilu Polyphenol 0,5g/kg TLCT/24h cao gdp 10-12 ldn lieu dimg cho ngudi theo kinh nghiSm dan gian, lien tuc trong 42 ngdy khdng lam thay ddi co y nghTa thdng ke ve su thay ddi trpng lupng, di?n tim, cdc chi sd huyet hpc, cac chi so sinh hda cr cac thdi diem xet nghiem cung nhu hinh dnh mo benh hpc gan, thgn thd giOa nhdm chung va nhdm thii.

4. Ket lugn

Lieu cao nhat 10,0g/kg ciia Polyphenol dua vdo theo dudng udng chua thay cd bieu hien dpc tinh cdp d chupt nhat trang.

Ket qud nghien cuu dpc tinh cap cho thay lieu dung ngp tdi da d chupt nhdt I Og/kg KLCT. Tren CO sd do lilu 0,5g/kg KLCT tuong ung 1/20 ciia lieu cao nhdt ndi tren dupc lira chpn de thii ddc tinh ban trudng dien.

Tdi lifu tham khao

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