FLAVONOID

Gio vin hng dn ThS.GVC. Nguyn Vn Hng Nhm thc hin ng Th Luyn Trn Gia Khang

Chu Vn Kim
Nguyn Thin Tho
12/7/2013

Nguyn Vn Nh

1. nh ngha, ngun gc, c trc, phn loi. 2. Tnh cht 3. Cc phng php nh tnh v nh lng 4. Cc phng php chit sut v tng hp Flavonoid 5. Tc dng sinh hc v ng dng

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1. nh ngha, ngun gc, c trc, phn loi. 1.1. nh ngha Flavonoid l mt nhm hp cht t nhin ln thng gp trong thc vt, phn ln c mu vng. V cu trc ho hc, flavonoid c khung c bn theo kiu C6 C3 - C6 (2 vng benzen A v B ni vi nhau qua mt mch 3 carbon) v c chia lm nhiu nhm khc nhau, y khng gii thiu v cu to ca tng nhm. Hu ht Flavonoid l cc cht phenolic
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1.2. Ngun gc Cng ging vitamin C, cc flavonoid c khm ph bi mt trong nhng nh sinh ha ni ting nht ca th k 20: Albert Szent-Gyorgyi (1893-1986). ng nhn gii Nobel nm 1937 vi nhng khm ph quan trng v cc c tnh ca vitamin C v flavonoid.

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1.3. Cu trc Flavonoids l mt chui polyphenolic gm c 15 nguyn t cacbon v hai vng benzen lin kt bi mt ng thng c 3 cacbon

Khung trn, c th c m t h thng nh: C6C3- C6

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Cu trc ha hc ca flavonoids c da trn c s l mt khung 15C vi mt CHROMANE vng thm B th hai v tr 2, 3 hay 4.

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1.4. Phn Loi: Flavonoid c cu trc mch C6C3C6, u c 2 vng thm. Ty thuc vo cu to ca phn mch C3 trong b khung C6C3C6, flavonoids c phn thnh cc phn nhm sau:

Eucoflavonoid
flavon, flavonol, flavanon, flavanol, chalcon, antocyanin, anthocyanidin Isoflavonoid isoflavon, isoflavanon, rotenoid Neoflavonoid calophylloid

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1.4.1. Eucoflavonoid

Flavon (= Flav-2-en-4-on)

Flavonol (= 3-Hydroxy-4-oxoflav-2-en)

Flavon rt ph bin trong thc vt: thng, hong cm(r), m (l). cy anh tho, cy la apirenin v luteolin
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Flavanon (= Flavan-4-on)

Flavanol (= Flavan-3-ol)

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chalcon

anthocyanin

anthocyanidin

Chalcon c ch yu trong mt s cy h Cc - Asteraceac tp trung nhiu nht v cy, g li (keo, bch n, d, u tng, trinh n hong cung, dng x).Khng tm thy ng vt.
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1.4.2. Isoflavonoid

isoflavan

isoflavonoid

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1.4.3 Neoflavonoid

neoflavan

Neoflavonoid

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calophylloid

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Phn t ca cc hp cht cc phn nhm trn u c 2 vng thm, mang nhm hydroxyl vi s lng v v tr khc nhau, ty thuc tng cht Cc hp cht ny c cu trc mch C6C3C6, nhng khung cu ni C3 gia 2 nhn th khc nhau ty thuc tng loi hp cht

Mch cu ni C3 c th l mch h (chalcon), mt vng n (flavanon) hoc vng c ni i (flavon,flavonol)

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2. Tnh cht

Flavonoid to c phc vi cc ion kim loi m chnh cc ion kim loi ny l xc tc ca nhiu phn ng oxy ha.
Do tng phn nhm ca flavonoid c cu to ring, chng va c tnh cht chung va c nhng khc bit v tnh cht vt l v ha hc Trong thc vt cc hp cht trn thng tn ti di dng hn hp ca cc dn xut, vi t l khc nhau, ty thuc ngun gc thc vt
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2.1. Eucoflavonoid
2.1.1. Flavon, flavonol - L hp cht phn cc nn tan trong nc, t tan trong dung mi hu c . - H t giy c nh dch chit trn ming l ammoniac cho mu vng sng . - Acid sunfuaric nh ln cc dn cht flavon, flavonol cho mu vng m - Dung dch SbCl5/CCl4: mu vng m

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2.1.2. Flavanon, flavanol

+ Cc dn xut flavan-3,4-diol u khng mu, c tnh quang hot. + Flavanon, flavanol c trong l, v hoc g ca mt s loi cy. Flavanon, flavanol l cc cht khng mu, nhng khi tc dng vi dung dch acid v c th c mu . + D b oxi ha v trng hp ha nn vic phn lp cht tinh khit gp kh khn.

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2.1.3. Chalcon
+ Km bn trong mi trng kim. + Tc dng vi dung dch FeCl3: cho kt ta xanh thm hoc xanh nht tu theo s lng nhm hydroxyl trong phn t. + D tan trong nc nng, ru, .to dung dch khng mu, khng tan trong cc dung mi khng phn cc hoc t phn cc nh benzene hoc chloroform. + Di tc dng ca H+ hoc OH-, chalcon c th chuyn sang flavanon + Khi to lin kt glycosid phn ng ni vo v tr 4, mt s 2.
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2.1.4. anthocyanidin, antocyanin + Anthocyanidin c tnh base mnh to thnh mui bn vi acid v c. + Chng to dung dch mu trong acid v mu xanh da tri trong mi trng kim. + dng base t do, anthocyanidin l cht ng phn vi flavanon. + L dn xut ca flavon m nhm carbonyl b kh thnh ru.

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+ Cc dn xut flavan-3,4-diol u khng mu, c tnh quang hot. + Khng mu, nhng khi tc dng vi dung dch acid v c th c mu .

+ D b oxi ha v trng hp ha nn vic phn lp cht tinh khit gp kh khn.

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+ Anthocyanidin thng tn ti di dng glycozit, gi l anthocyanin.

+ Mt vi hp cht kiu anthocyanidin
OH OH HO O OH OH melacacidin OH

OH OH HO O OH OH ( ) leucorobinetinidin OH

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2.2. Isoflavonoid (isoflavon, isoflavanon, rotenoid)

Isoflavonoids tt c khng c mu sc. N c to thnh t axetat theo c ch ng vng vi phenylalamine, cinnamate dn xut c st nhp vo vng B v C-2,-3, v-4 ca d vng.

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3. Cc phng php nh tnh v nh lng

3.1. nh tnh

Flavonoid l mt nhm hp cht t nhin ln thng gp trong thc vt, phn ln c mu vng
+ Cc cht thuc nhm leuco-anthocyanidin do khng c ni i lin hip gia vng B vi nhm carbonyl nn khng mu. + Cc dn xut anthocyanidin th mu thay i ty theo pH ca mi trng.

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C th dng cc thuc th sau:

+ Hi amoniac : Vt flavonoid cho mu vng. C th quan st nh sng thng hoc di n t ngoi (bc sng 366nm) trc v sau khi h amoniac.
+ Thuc th Benedic : Ho tan nng 173g natri citrat v 117g natri carbonat trong 700 ml nc, lc nu cn. Ho tan 17,3g ng II sulfat trong 100 ml nc. Trn ln 2 dung dch trn, khuy u. ngui hn hp ri thm nc va 1000ml Cc flanon v flavonol s cho vt mu vng trn nn l nht vi thuc th ny
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+ St III clorid 3% trong ethanol : Tu theo s lng v v tr ca nhm OH phenol m cho mu lc , xanh hoc nu + Thuc th acid boric acid oxalic : Gm 15 ml dung dch acid boric 10% v 5ml dung dch acid oxalic 10%. Sau khi phun sy bn mng 1200C trong 10 15 pht, cc flavon v flavonol pht quang mu lc hay vng lc + Thuc th Diazo : Cc dn cht flavonoid c nhm OH v tr 7 c th kt hp vi mui diazoni to thnh cht mu azoic mu vng cam n
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+ Thuc th nhm clorid: to phc mu vi flavonoid Bn mng sau khi phun dung dch AlCl3 1 % trong methanol c sy 1200C trong 5 pht , quan st vt nh sng thng hay di n t ngoi, bc sng 366nm + Mui ca kim loi khc: nh dung dch nc bo ho ch acetat cho mu vng vi flavon, mu cam vi flavonol + Thuc th acid sulfuric 80%: c tc dng kh nc chuyn leucoanthocyan thnh anthocyan c mu

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+ Thuc th NP/PEG : Phun dung dch Difenylboryloxyethylamin 1% trong methanol, sau phun tip dung dch PEG 4000 5% trong cn soi di n UV- 366 nm

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3.2. nh lng
Tu vo tng loi Flavonoid m ta c phng php nh lng c th khc nhau

V d:
a. Flavon hoc flavonol Phng php cn: ng dng khi nguyn liu giu c flavon hoc flavonol v dch cht t tp cht .

o mu: bng phn ng cyanidin, phn ng kt hp vi mui diazoni, to phc mu vi AlCl3 , mui titan, chrom Phng php o ph t ngoi.
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b. Chalcon
Phng php phn tch HPLC (sc k lng cao p). Vi pha ng l dung dch acetonitrile v acid H3PO4 1% (phng php chun trong phn tch) Phng php so mu: c nhiu phng php so mu khc Phng php Folinciocalteu: (hn hp mui phc polyphosphotungstate - molydate) + Rt nhy i vi cht kh, trong mi trng kim nh th s b kh thnh sn phm phc molydenium tungsten c mu xanh. + Sau em o hp thu A (chalcon ch hp thu mnh vng 300 400nm)
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 Phng php Prussian Blue:

+ Hn hp thuc th l FeCl3 v K3Fe(CN)6 b kh bi cc hp cht phenol v to thnh phc ferric (III) hexacyanoferrate (II) c mu xanh. + yn dung dch trong 15 pht, sau em o hp thu A

Phng php Diazotized

+ Da vo kh nng phn ng ghp i vi hp cht diazo trong mi trng acid to thnh hp cht c mu vng c trng. + Lc u, yn dung dch trong 1 gi, sau em o hp thu Phng php Vanillin HCl: to thnh hp cht c mu .
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4. Cc phng php chit sut v tng hp Flavonoid 4.1 Chit sut

Nguyn liu c chit vi methanol, bc hi methanol trong chn khng hay trn ni cch thu ti cn. Ho tan cn trong nc ri chit li bng ethyl acetat. Bc hi dch chit ethyl acetat trn cch thu ti cn. Ho tan cn trong methanol chm sc k hoc c th dng dch chit methanol ban u lm dung dch chm sc k
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Khng c mt phng php chung no chit sut cc flavonoid v chng rt khc nhau v tan trong nc v trong cc dung mi hu c. VD: Vi cc cht anthocyanin thng km bn vng nht l cc acyl anthocyanin c acyl ha vi cc acid aliphatic do ngi ta thng chit bng methanol c mt ca cc acid yu nh acid acetic, acid citric, - Cc dn cht flavon, flavonol c nhm -OH t do v tr th 7 tan c trong dung dch kim long, da vo chit .
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- chit cc dn cht dng glycoside, ngi ta phi loi cc cht thn du bng ether du ha sau chit bng nc nng hoc methanol hoc ethanol hay hn hp cloruafom v ethanol - Dch chit em lm m c di chn khng nhit thp (40-70 C) .

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- phn lp tng cht flavonoid, ngi ta dng phng php sc kh ct .

Cht hp ph
Cht hp ph thng dng cho sc k cc flavonoid l silicagel G, bt polyamid, thng hot ho 1200C trong 1 hoc 2 gi. Ngoi ra cn c th dng cc cht khc nh bt cenllulose, silicagel, magnesol,

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 Dung mi

i vi lp mng silicagel G
+ Tch cc Aglycol : Toluen ethyl formiat acid formic (5:4:1) + Tch flavon: Benzen aceton (4:1), (9:1) ; Benzen ethyl acetat (3:1) Ethyl acetat Methanol (4:1) + Tch cc flavonol: Ethyl acetat methanol (8:2) Benzen pyridin acid formic (36:9:5)
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+ Tch cc flavonoid glycosid : Ethyl acetat acid formic nc (8:1:1) ; Butanol ethyl acetat- dimethyl formamid nc (10:6:3:2) Ethyl acetat methanol nc (10:2:1), (100:16:14) Toluen ethyl acetat aceton acid formic (15:2:2:1) Cloroform methanol (9:1) Ethyl acetat acid formic - acid acetic khan nc(100:11:11:27)

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 i vi lp mng bt polyamid
Methanol nc (8:1); (4:1) Ethanol nc (3:2), (4:1) Ethyl acetat methylethylceton acid formic nc (5:3:1:1)

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4.2. Tng hp

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5. Tc dng sinh hc v ng dng

5.1. Tc dng sinh hc - Cc dn cht flavonoid c kh nng dp tt cc gc t do nh: HO ROO Cc gc ny nu sinh ra cnh cc DNA s gy ra nhng nguy hi nh bin d, ung th, tng nhanh s lo ha. - Khi a cc cht chng oxy ha nh flanovoid vo c th bo v t bo th c th ngn nga cc nguy c x va ng mch, tai bin mch, lo ha,V kh nng chng xy ha ca flavonoid cn mnh hn cc cht khc nh vitamin C, E, selenium v km.
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- Flavonoid to c phc vi cc ion kim loi nh cc phc:

o o o
o o

o o

Me

Me Me Oxychromon Oxycarbonyl Orthodioxyphenol

M chnh cc ion kim loi ny l xc tc ca nhiu phn ng oxy ha

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- Tc dng chng c ca flavonoid lm gim thng tn gan, bo v c chc nng gan - Flavonoid th hin tc dng chng co tht nhng t chc c nhn (ti mt, ng dn mt, ph qun v mt s t chc khc). - Trn b my tit niu, nhiu flavonoid thuc nhm flavon, flavanon, flavonol th hin tc dng thng tiu r rt. - Tc dng chng lot ca flavanon v chalconglycoside ca r cam tho c ng dng cha au d dy
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V mt s cc tc dng khc,

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5.2 ng dng
- Flavonoid lm bn thnh mch, gim sc thm thu cc hng cu qua thnh mch ng dng trong cha tr cc ri lon chc nng tnh mch, gin hay suy yu tnh mch, tr, ri lon tun hon vng mc. - Cht flavonoid t l cy chay gip bo qun m thn, c ch phn ng thi ghp thn; yu t bo v thn ghp, hn ch tn thng t bo thn do thiu mu

Cy Chay (Artocarpus tonkinensis A chev)

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H Du tm -MORACEAE

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- Flavonoid c chit t l cy bch qu (Ginkgo biloba-thuc h Ginkgoaceae) cha cc cht dn cht ca Kaempferol, quercetin... c tc dng ci thin c tun hon, c bit l tun hon no, lm tng tr nh, c tc dng tnh cc trong cha bnh Alzheimer, ci thin chng lit dng.

L cy bch qu (Ginkgo biloba ) Thuc h Ginkgoaceae

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- Th nghim flavonoid chit xut t hoa kim ngn cng c tc dng lm gim cc ch s cholesterol ton phn, triglycerid v LDLC (hi cho tim) ng thi lm tng HDLC (li cho tim mch) trong huyt tng chut cng trng ung cholesterol thc nghim.

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Tn khoa hc Lonicera Japonica Thunb H cm chy (caprifliaceae).

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- Cc flavonoid cn c tc dng chng c, lm gim thng tn gan, bo v chc nng gan nh cynarin, acid cafeic, chlorogenic... c trong cy actis (cynara scolymus L )
- Bo The Times of India dn li cc nh khoa hc cho bit, Chnh hp cht flavonoid c trong c hnh vi c tnh chng xy ha gip tiu dit cc phn t gc t do. C hnh c tc dng nga ung th(c bit l ung th d dy), huyt p cao v bnh tim, gip gim cholesterol v ngn nga chng x va ng mch, qua gip nga bnh tim.
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-Trong n hoa he c cha flavonoid: rutin (rutosid) cao nht. Tc dng ca rutin (mt loi vitamin P) lm gim tnh thm ca mao mch, cng c sc bn thnh mch, hn ch hin tng suy gim tnh mch ngi cao tui.

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Tn khoa hc: Sophora Japonica L H cnh bm (Papilionaceae).

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- Cy thanh hao hoa vng cha cc hp cht flavonoid gm quercetagetin, methylether, tetramethylether... v cc coumarin, cc dn cht polyacetylen Tn khoa hc l Artemisia annua L Thuc h cc Asteraceae

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-Hesperidin v naringin l hai cht flavonoid c trong bi gip bo v tnh n hi ca mch mu, nga x cng ng mch, gin tip chng cao huyt p v tai bin mch mu no -Nghin cu cho thy cc cht c trong chocolate c gi l flavonoid c th gip mch mu hot ng tri chy hn v c th gim nguy c bnh tim.

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- Mt nghin cu mi ca M c ng trn tp ch Journal of Agricultural and Food Chemistry khng nh rng cc cht flavonoid trong chanh c tnh nng ngn nga cc bnh thoi ha ca no -Ngoi ra, flavoloid cn c trong mt s loi nh: cam qut, v v ht nho, u nnh

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TI LIU THAM KHO Theo cc a ch Website sau:

http://www.chem.qmul.ac.uk http://commons.wikimedia.org http://suckhoecongdong.com http://herkules.oulu.fi http://www.microbialcellfactories.com www.baomoi.com www.tintuconline.vietnamnet.vn http://www.suckhoe360.com www.nutifood.com.vn http://pharm1.pharmazie.uni-greifswald.de http://vimes.com.vn http://www.nobel.se http://www.evitamins.com http://www.sciendaily.com http://www.herbalchem.net http://www.springelink.com http://www.genetics.org http://www.blackwell-synergy.com

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