Luận án Ảnh hưởng của dịch chiết chứa saponin triterpen từ một số cây trong họ araliaceae đối với hệ enzym monooxy genase

a'td. cacthaidiemrhead6ithaigianngucuachuQt d~ukh6ngtangsovoi chuQtblnhthuang. 125 fu.'llsosanhthaigianngud210chuQtdi~uhi bangSVN vaK92,chungta coth~nh~ndinhrang:hi~ul1,tcphl,lch6ienzymchuy~nh6atrenchUQtgaynhi€m X<:ila docachQpchfitSaponinhQNhansamhi~ndi~ntrongK92. 3.6.2.Tacd~ngbaov~gallcuaK92trenchuQtdfitiemacidAcetic. Trongquatrinhthl,tcnghi~mtimhi6uanhhuangcuaK92d6ivoi lacd1;mg giamc!2.UcuaParacetamo1tIeDchuQtgaycon datiqu~nb\mgbangacidAcetic, chungtoi thfiyd 10chuQtdffdi~utribangParacetamo1c6nhi~uchuQtche'tnii rac sailthinghi~mill'ngay1ngayd€n ngay6,bang3.26th6ngketl1~chuQtch6t ciladc 16thinghi~m. Bang3.26:TlI~ chuQtchttsaukhisU:d1:lngacidAceticquadllimgtiemphucmo d 16chuQtchitiemphucmodungdichacidAcetic0,7%(0,1m1/l0g)c6 2/12chuQtch6tsail till nghi~m.Trong khi d6 a16di~utri bangParacetamol 200mg/kg sO'chuQtch6tangrfitcaD(13/18),giai ph~uchuQtsail khi ch€t d~u thfiyco hi~ntuQnggallbi phun~,chill gallba fiat,mall gall nhQtnh~t,chothfiy , dA h .? . kh/muc Q.--I}~Ltligall a caD. ParacetamolduQccoi 1amQtchfitdQcvoi gall, d~cbi~tkhi co th6thi6u Glutathionethl dQctinhcangtangdohi~ntuQngperoxytmangt6 baagall [159]. TrenchuQtdffchou6ngParacetamol200mg/kg,chti':::Danggall giamdonguycd ho<:iitti'gall,kha DangAcetyl hoaclinggiam,VI th6 chuQtbi ch6tco th6la do nhi~mGQcacidAcetic. I Lathli'nghim S6SVTN sO'chuQtch6t % ch6t [iI i I I BInl1thuang I I 12 2 16,67I I K92(20mI/kg) 12 a a [ I Para (200mg/kg) 18 13 72,22 I F'ar<l+K92 10 0 0II L-.. I 126 Khi dungK92chungvdiParacetamol,khangghinh~nthftycohi~ntu'Qng chuQtche'tsail6 ngaytheodoLC6th6nh~ndinhd.ng:K92cokhananggiam dQctfnh'cuaParacetamolvaacidAcetic. 80 70 60 .50 40 30 20 lOJO. BT K92 Para Para+ K92 mnh 3.20:TlI~Chlli)tchefsaukhigaydaublingacidAcetic 3.6.3.Tac dQ.ngphQ.ch6ienzymchuy~nboaamiDSGPT cuaK92trenchuqt nhiitdiigaynhi~mdqcgallb~ngCCI4. Bang3.27:Hamlu{/ngSGPT(ALiT) trenchui)tgaynhilmdl)cganblingCCl4 Sail khi tiemphticma CC4 O,O5ml,hamluQngGPT trongmallchuQtang 2,2- 2,8l~n(dQtinc~y99,9%),chungtoc6tinhtr.;mgbuyho~ite'baanhuma galltrendQngv~tthi nghi~mdo CC14.C5 16khangdi~uhi, de'nngaytht17 men gallv~ncaohon1,96l~nsovditrudckhigaydQc.Trangkhido,mengallcua La thi sO' I Trudckhi HamIU<;1ngGPT (UIIl) sailgaydQCCC4 nghim SV I gaydQC 1ngay 3 ngay 7 ngay BlnhthU<1ng 10 57,0:t11,2 55,8:t10,4 63,1:t 7,24 56,2:t16,6 CC4+H2O 10 59,7:t8,9 130,5:t19,3*** 164,7:t24,2*** 117,1:t17,5** CC4+K92 10 62,1:t 16,5 78,3:t19,7* 82,5:t 9,96* 61,2:t16,7 127 chuQttrong16di6utri b~ngK92 tangit bon,khoang1,4l~nd ngaythli nh:Itsail gaydQC(dQtinc~y95%),valId v6gioi h~nblnhthuongsail7 ngaydi6utrio CC14khivaocoth€ segiaiphongcacg6ct1tdocl*,CytP-450dongvaitra quailtrQngtrongvi~clo~icacgoctl..1'do nayva MRz clingvoi cach6nhQp Saponinroanph~ncuaSVN di gapph<lnthlicd:1yquatrinhlo~idQccuacac Monooxygenasenay[51],[52],[53],[76],[86]. 180 160 140f- :l. 120..:; ~100 0 r~ 80 ffi 60 1:. 40 20 0 --+--BT ---8--' cc11- , -".-- ccl1+K92! TruoeTN 1 3 Thoidi::m1 7 Bini.!3.21:HamlU:(lngGPT (ALAT) trenchuQtnhdtgaynhilm dQcbang Terracloruacarbon Ph6ihQpvoike'tquabang3.22,3.23va 3.24,xacdinhduQCrftng:ch6 ph:1mK92 la cokhananggaycamlingva lamtangsinhht$Cyt.P-450,quado d:1ynhanhquatrmhlo~ig6ct1tdoxayrat~igall. 3.7. Thamdolac dQngcuaK92tren quatdnh chuy~nhoachfftl~ GangillvaitraquailtrQngtrongchuy€nhoacacch:It,d~cbit$tla chuy€n hoathu6c.Nhi6u thu6cduQcoxyhoaquamicrosomeegall voi sl..1'thamgiacua CytP-450. Cac enzymchuy~nhoathu6ccuamicrosomeegall co th€ duQcearn ling bdi cac hoa ch:It (thu6ctri.fSail co Clo nhu'DDT, Lindan...),ho~cthu6c 128 (Phenobarbital,Rifampicin,Diaezepam...)h~uquala nhi€u thu6cbichuy~nhoa nhanhvamc1ttacdl,mg[1],[5]. Thu6ckhiVflOcoth~thuongduQcchuy6nhoaqua2 pha:phaI g6mcac i phanungoxyboa,khl1ho~cthiiyphan;phaII la nhungphanunglienhQp[5], [134]. Codein(alkaloidcotacd~gchinhla giamho)bi chuy6nhoaquaCyt.P- 450nhophanlingQ-khitmetyl(pha1)t~othanhchelfmeltacdl,mg[I11],[134], [152]. Morphin(alkaloidcotacdvnggiamdatim~nh,nhungtacdvnggiamdati l~iy€u honCodein)bi N-khitmeryl(phaI) va glucurolienhQpa microsomee gall d6 cho Morphin-3-monoglucuronidmelt ho~t tinh va Morphin-6- monoglucuronidconho~tinh[Ill], [136],[155]. Cacke'tquachungtoi thuduQctuthvcnghit%mdffchungtoche'ph~mK92 cotuongtacvdih~enzymchuy~nhoa(ph~n3.4),t11doco anhhuangde'ntac dvngcuacacthu6cduQcchuy~nhoat~igall(ph~n3.5va3.6.1.4).Trudckhitim hi6utacdQngcuacacSaponintriterpentrongK92 trenquatrinhchuy~nhoa thu6ct~igall,chungtoi khaosatsv thayd6i tacdl;mggiamho,giamdaticua Codein,MorphintrenchuQtdffchositdl,mgPhenobarbital- mQtchelfearnung enzymMonooxygenasekinhdi~n. 3.7.1.Khao satannhudngCIiaPhenobarbitaltren tac dl}.ngiamGauCW:L MorphinvaCodein: TrenchuQtnhatdffduQCgayearnungenzymbiingPB,chungtoikhaosattac dt,mgiamdaticuaMorphinvaCodeind~ki6mchunghit%uquakichho~tenzym cuatrenmohinhgaydatibiingacidAcetic(bang3.28) 129 Bang3.28:s6 tanxuathi~ncandautrong20phutcuachui)tbinhthuifngva gayearnlingbdngPhenobarbital 30 25 5 0 ,- :8NC! i~PBI ==20:-:: '0 ,:: 15~ ';55 10 MOrp,r. code;' La thinghit$ill mnh 3.22:s6 tanxuathi~ncandautrong20phutcitachui)tbinhthuifng vagaycamlingbdngPhenobarbital PhenobarbitalEimgiamtacdl,mgucchedaticuaMorphin(4,9l~n),cua Codein(2,3l~n).Ke'tquath1!Cnghi~mnayhoantoanphuh<;1pvoily thuye'tkinh di6nv~khanangho~thoah~MonooxygenasecuaPhenobarbital,quad6lam Uing-chuy€n-hoa,tangthaitrU'chiltl~,lammilttaGdl,mgcuaMorphinvaCodein, [124]. Tli ke'tquatren,choph6pchungtoisli'dl,mgmohinhgaydatid6khaosat chuy€nh6acuaCodein.Morphindu'oianhhu'angcuacacchiltc6khanangtu'dng tacvoi enzymchuy€n h6achilt l~cua microsomeegall, voi chiltd6i chungla Phenobarbital. SIT Thu6cthli'nghim ! S6ln daticua10chuQtdiu tribftng Morphin Codein 1 Nu'occilt 5,5:t0,41 100% 6,5:t0,41 100% 2 Phenobarbital 27,0:t2,15 490,9% 15,0:t2,15 230,8% 130 3.7.2.Khaosatanhhu'dngcuaK92trentacdQnggiamhocuaCodein: CodeinlamQthu6cgiamhokinhdi€n, la mQtlo<;tithu6cehuy€nh6at(;ligall. Chungtoi etati€nhanh thl1qghi<$mtacd~nggiamhocuaCodeintrenehuQtda duQchou6ngeh€ ph~mK92,sosanhvai16chung(u6ngnuaceftt)va16sitd~ng ehfttearn1i'ngenzymd6iehi€u(Phenobarbital),k€t quatrinhbaytrongbang3.29 Bang3.29:Socan hotrong5phzitcuachuQtuongCodeinvagaycdmung K92,Phenobarbital Codeinh€u 45mg/kglamgiamr6r<$ts6l~nhocuachuQtsovai 16ch1i'ng.K92 khonganhhuangd€n lac d~ngeuaCodeineNhungtrenW chuQtduQcho<;tthoa enzymb~ngK92 thi lacd~ngliech€ canhocuaCodeinda giamc69ngma th6ngke, va theechi€u huangtu'dngt1;1'nhuPhenobarbital. S1;1'thayd6i lac d~nggiamho cua Codeinduai anhhuangeuaK92 va Phenobarbitalc6th€ duQc19giainhusail: Trong qua trinh chuy€n h6at<;tipha I, Codein (thu6cc6 lac d~nggiamho ffi<;tnh)bi 0 - demety1h6aboicaeenzymMonooxygenasechuy€n thanhMorphin (thu6cgiamdatim<;tnh,nhunggiamhoy€u honCodein).PhenobarbitalvaK921a nhU'ngehfttcam1i'ng,lamtangsinhh<$enzymnay,dod6 thucd~y quatrinhbi€n STT Thu6cthl1nghi<$m S6ln ho TI1<$%sovai %giamho ch1i'ng 1 Nuaccftt 36,8:t5,25 100 o 2 K92 I 35,2:t6,00 95,7 4,3 I 3 Codein 12,45:t2,05 33,8 66,2 4 I PB +Codein I 18,74:t3,03 50,9 49,1 5 K92+Codein 17,52:t2,74 47,6 52,4 131 d6iCodeinthanhMorphintrongpha1.VI the',chuQtd 10u6ngPN +Codeinva K92+Codeinhonhieuhan10chiu6ngCodein. 40 35 30 .2 25 c: '~ 20 a 15 10 ,5 0 C K92 Co PB+Co K92+Co L6 thinghi~m IDnh 3.23: SosanhsffltindwQthotrong5phutcuachul)tnhiitblnhtlutiJng vachul)tdu(!cgaycarnzingbeIngPB, K92saukhichou5ngCodein30phut 3.7.3.Khao satanhhu'dngcuaK92trentacdQngghimdaDcuaCodein: Bang3.30:S5ltinxuathi?nC(/ndautrang20phutcuachul)tu5ngCodeinvagay earnzingblingK92,Phenobarbital STT Thu6cthti'nghi<$m S61§ndati TI 1<$% sovdi % giamdati chung 1 Nudcca't 43,4:t4,70 100 0 2 K92 41,5:t4,19 95,6 4,4 3 Codein 6,85:t0,70 15,8 84,2 4 PB +Codein 15,75:t2,20 36,3 63,7 5 K92 +Codein 3.58:t0,32 8,3 91,7 132 NgOaltac dl,1ngiamho, Codeincon co hi~u1\;1'cgiam dati.s6 li~uthu duQctrongbang3.30chotha'ycosl;1'thayd6itac dt,mggiamdaticuaCodeinkhi coanhhuangcuache"phefmJ(92. CodeinIi~u45mg/kgcotacdl;mgiamdatira'tm~nh,ticche"84,2%s6con datisoVOl16chung.TrenchuQtnh~tdffchou6ngK92 3 IfintruockhistYd~ng Codein,sO'condaticuachuQtdffgiamgfin1/2soVOl16chiu6ngCadell (coy nghlath6ngke,dQtinc~y99,9%).Vi K92hoanroankh6ngco hi<$uquagiam dati,Denkh6ngth6chor~ngco s1;1'cQnghQptacd~nggiii'a-K92va Cadell. Phil changIa do K92 thtic defyqua trlnh O-demetyl d6 chuy6n Codein thanh Morphin? 50 45 40 ::: 35 ,g 30 c 25"0 :.> '<0 20 C/) 15 10 5 0 C K92 Co PB+Co K92+Co La thinghi~m ffillh 3.24:Sosanhso lanxuathi?nC(Jndautrang20phutcuachuQtblnh thu:iJng,chUQtgaycamlingbangPE, K92saukhi u6ngCodein30phut 3.7.4.Khao satanhhu'dngcuaK92trentacdt;mgiamdaucuaMorphin: MorphinduQcxe'pvaonhomthu6cgiamdatim~nh,clingIa thu6cduQc chuy6nh6at~igand6chodftnsua'tchuy6nhoagiamho~cma'tacdl,1ngiam 133 dau.Ke'tquatrongbang3.31chothtyras1,1'thayd6ihic$u11,1'ccuaMorphinduoi anhhudngcuache'phftmK92 vaPB. Bang 3.31:S6 ltinxuathi?ncandautrang20phuteuaehut)tiernduaida i\1orphinvagayearnangblingK92,Phenobarbital 50 45 40 ::! 35 ~ 30 i3 25 u . '<0 20 r.I) 15 10 5 0 c K92 MO PB+Mo K92+MO La thinghi<$m mnh 3.25:Sosanhs6 ltinXllathi?ncandautrong20phuteuaehut)tblnh thuiJing,chut)tgayearnU'ngblingPB, K92 saukhztiernMorphin30phut Morphin(li~u5mg/kg)comcdl:mgiamdatirtt m<;tnh,ucche'86,75%sO' condatisovoi16chung.K92kh6ngcotacdl,mggiamdati.Khi chochuQtu6ng SIT L6 S61n dau % sovdi chung % giamdati 1 I Chung 43,4:i:4,70 100 0 2 K92 41,5:i:4,19 95,6 4,4 3 I Morphin 5,75:i:0,63 13,25 86,75I 4 PB +Morphin 27,00:i:5,30 62,21 37,79 5 K92 +Morphin 9,50:i:1,45 21,89 . 78,11 134 K923 l~ntn1'ackhi tiemMorphinthls6candaticuachuQtanglen65,22%so vai10chuQtchidungMorphinrheachi€u huangtu'angt1,(vaiPhenobarbital.Do do, co kha nangK92 cling gi6ngnhu'Phenobarbital,da ho~thoa enzym MonooxygenasedSthucd~yquatrlnhN-demetyl. Cacbang3.29,3.30va3.31chothfiyK92daanhhu'angde"nchuySnhoacua MorphinvaCodein(2alkaloidcocfiutruckhagi6ngnhau),varheachi€uhuang tu'angt1,(nhu'Phenobarbital. V~ythanhph~n aGtrongK92gaylenhi~uungnay?f)~Hmhi~uvaitracua Nhansamtrongche"ph~mK92.trongcacthtl'nghi~mtie'prhea(ph~n3.7.5), chungtoi sl'tdl,mgmohlnhgaydaubangacidAceticd~khaosattacdl,mgiam daucuaMorphinvaCodeinduaianhhuangcuache'ph~mK92,d6i chie'uvai che'ph~mK92da10';libeNhansam(K92khongSam). 3.7.5.Khaosatanhhu'dngcuaNhansamvaK92trentacdt;mgiamdau (:uaMorphinvaCodein: DicDchie'tNhansam(co51,(hi~ndi~ncuaSaponintriterpen)aac!uQc chungminhco khanangtu'angmcvai enzymchuySnhoathongquacactJ."l1,(c nghi~mphan3.3.che'ph~mK92clingcohi~uquatu'angt1,(ph~n3.4).Calihei duQCd?traa dayla:SaponincuaNhansamcophaila thanhph~ndongvaitra quye'tdinh tronghi~ul1,(camlingenzymcua che"ph~mK92 hay khong?Cac thanhph~ncanl';li(7 du'Qcli~u)cuache'ph~mK92 co vai tra nhu'the"naG?Ne'u khongcos1,(hi~ndi~ncuaNhansamthlK92coth~tu'angtacvaienzymchuySn hoadu'Qckhong? 135 f)~coth~giaidapphcin aonhungdiuhoitren,chungtoikhaosattac dl:mgiamdaticuaCodein/Morphintrencae16ehuQtdiiehou6ngehe'ph~mK92 vaK92khongcoNhansam. Bang3.32:St/ttinxu{{thi~necJndautrong20phuteuaehuQtLIangCodein ho(ictiemdl1aidaMorphinvagayearnWIgbangNhansam,K92 :3 ~ "0 i::: '0 (,) '<0 (".I) 10 9 8 7 6 5 4 3 2 1 0 8NC I ~ K92-NSI I ONS i D-K92 Morp,il coreil Thuocgiamdau IDnh 3.26:Sosanhsa ttinxuathi~ncandau trong20phutcuachuQtnhdt blnhthl1iJngvachuQtgayeam[i:ngbangNhansam,K92saIlkhi dungthuac giamdau30phut STT Lo thil'nghim S61cindatieua10diu hi bng Morphin Codem 1 N\idccat 5,5:t0,41 100% 6,5:t0,41 100% 2 K92khongNS 5,0:t0,32 90,9% 6,3:t0,45 96,9% 3 Nhansam 6,5:t0,45 118,2% 5,0:t0,45 76,9% 4 K92 9,5:t0,43 172,7% 3,0:t0,45 46,2% 136 Khi lo~iboNhansam,cueph~mK92 khongcongayannhll'dngdenhit%u ll!cgiamdaucuaMorphinvaCadellnua. DungNhansam(li~u20g/kg)3 l~ntru'dckhi gaymohInhGall,dfflamtang 23,1% lacdl:mgiamdaucuaCodein,nhll'ngvdiMorphinl~iticcue18,2%tile dl;lngnay. K92 clingchohit%uling cunghll'angvdi Nhan sam,nhll'ngm~nhhdn:tang 53,8%tacdl;lngcuaCodein,vagiam72,7%lac dl;lngcuaMorphin.Trangkhido, hamlll'<;1ngNhansamtrongK92chib~ngkhoang1/10 sovdi 10chidungrieng Nhansam(Nhansamchiemtilt%9,375%trongcongthliccuaK92).f)i~unayco th6la dos1,1'tll'dngtaccuacacSaponin.triterpenNhansamvdi cacthanhph~n conl~icuaK92. M~cduchll'acodi~ukit%nd6khaosattit ca.cacthanhph~ncotrongcue ph~mK92'd6ivaiquatrlnhchuy€nhoaMorphinvaCodein,nhll'ngketquacua th1,1'cnghit%mlo~itrU(ph~n3.7.5)offchlingminhvai trocuacaeSaponintriterpen Nhansamtrongd6ivdi enzymchuy6nhoa. TheoTheoTestaB. vacs..cacchitgaycamlingthuQctypPhenobarbital lamtangsinhCytP-450[109],[110],[155],dodolamm1tlacdl,mgcuaCadell vaMorphin. Ket quath1,1'cnghit%mchungtoi thudll'<;1choanroanphuh<;1pvai cae tai lit$utrongvangoainll'dedffcongb6 trll'dcday,chophepchungtoi comQtso' nh~nGinnband~uv~annhll'angeuaK92tren2 d6itll'<;1ngCodeinvaMorphin nhll'sau: K92 lamtangsinhCytP-450,quado lam m1tlac dl;lnggiamhocua Codeintll'dngtl! Phenobarbital.Trongqua trinhchuy6nh6athongquacae Monooxygenaset~igall, Cadell bien thanhMorphin qua phanling O-demetyl 137 trongphaI cuaquatrinhchuy6nhoa[136],[155],dodo10chuQtdl1Qcgayearn lingbflngK92honhi€uhall,nhl1nglq.idatiithansovdichuQtblnhthl1ong. K92lamtangsinhCyt:P-450,tangchuy6nhoaMorphin,lamchoMorphin nhanhchongbimit lacd1,1ngvdibi6uhi~nla lacdl,mgticch€ daticuaMorphinbi giamdi. D6 rimhi6uxemcophaicornQtphftnCadell trongco th6dl1Qchuy6n hoathanhMorphinhaykh6ng,chungt6il~pbang3.33d6sosanhlacd1,1nggiarn dan,trongdo liy Morphinlamchit giamdatichuinvdihi~uquagiarndatila 100%. Bang3.33:Sosanhtacd~l1g iamdaucuaMorphinvaK92+Codein 45 40 35 ;:! 30 ;";1 ~ 25 B 20 a 15 10 5 0 K92 Me Co K92tCo Lo thinghi~m ffinh 3.27:Sosanhs6'C(Jf1daucuacacL6chUQtsad~ngMorphin vaCodein+ K92 5TT L6 th1l'nghirn sO'candati % giamdati i 1 K92 41,5:t4,19 0 '1 Morphin 5,50:t 0,41 100"'-' 3 Codein 6,85:t0,70 83,50 4 K92 +Codein 3,58:t0,32 153,63 138 Trangdi~uki~nchuy~nhoacuacoth~binhthuong:Codeingiamdatiye'u honMorphinva co khoang10%luQngCodeinduQcchuy~nthanhMorphin,vi the'phaith~ntn;mgkhisadl;mgCodeinli~ucao[136};SlIcomi;itcuacacSaponin trongK92dalamtang.sinhenzymchuy~nhoa,thucd~yquatrlnhoxyhoakhli metylcuaCodein,nenlamtangs6luQngMorphintrongco th~,ph6ihQpvdi phc1nCodeinconl~i,khie'nchotic dl,mg iamdaticua10chuQtu6ngK92ph6i hQpCodeinm~nhhonkhi chi511d~ngCodeinhoi;icMorphinriengIe. Theocacbang3.29,3.30va3.31,K92 cokhanangcamungvdienzym chuy~nhoa thu6c t~i microsomeegall rhea ki~u Phenobarbital. Nhung ali~u khaosat (20gduQcli~ukho flAgth~tn;mgchUQt),che'ph~mK92 th~hi~ntac d~ngkhongtri~td~nhu ch:ltd6'ichungPhenobarbial,phai changla do K92 khongphailamQtdoncha'tvacoslltuongtacgifi'acacthanhphc1ntrongK92vdi nhau?Phaichangtacdl,mgchuyellcuaK92la a phaI cuaquatrinhchuy~nhoa: giaido~nCodeinthanhMorphinquaCrt P-450nhophanungO-demetyl[136], [142]. Trangtu'onglai,cc1nphaitiert~ckhaoCUlld~lamsangtova'nd~nay. M(}t56tieuchufi'ncuache'phfi'mK92 dcacthinghi~mtuphc1n3.4de'n3.7noitren,K92daduQcchungminhla mQtche'ph~mco tacdl,mg iaidQc,co khananglamthayd6ihi~ull1ccua4 3.8. nhomduQcph~mdi;ictriof)~codi~uki~nduache'ph~mK92 tra thanhmQtche' ph~md~ttieuchu~nduQcphepsli'd~ngtrennguoi,chungtoi tie'nhanhcackaho satmQtvai thongs61yhoavadQctinhcuaK92. 139 3.8.1.TH~uchuin ly boa: - M~lUsa:c:chc1tlongmaumiud~m,trong(d~lauco th~coit c~nla:ng, nhungkhi la:cse tand€u). Mlii vi: mlii thornd~ctru'ng,vi hoingQt,d~uO'ng. - 8Q c6n:10:t2% Hamlu<;jngSaponinroanph~ntrong100ml:33,15:t7,25mg%. 3.8.2.DQctinhca'pcuaK92 ThatrenchuQtnha:tdngd 2 phaicotrQnglu<;jng20:t 1g,sO'luQng:30 can. Sailkhichom6ichuQtuong1mlche'ph~mK92dffcod~ct6idad6ndQco th~borndu<;jcquakimVaGd~daychuQt(tuongduong270m1'kgth~trQng,gc1p 13,5l~nli€u sa dl,mgtrenchuQt).chungtoi thc1ychuQtco xuc1thit$ntrit$uchung giamv~ndQngsailuO'ngthuO'ckhoang30phut,r6isau dokhoang60phutchuQt trdl~iho~tdQngbinhthuang.Trangthaigianquailsatla 48gia k~tukhicho uongthuoc:khongcochuQtche't. Nh4nxi!: che'ph~mK92codQanroancaD,chuaxacdinhduQcli€u toi thi~ugayche'trenchUQtnha:ttra:ngkhisadt;mgduanguO'ng. 140 3.8.3.A.nhhuangcuaK92 trenmt}tvai chIs6sinhhQccuachuQtnhilt(dt}c tinhbantruongdi~n) 3.8.3.1.Khaosatanhhudng,cuaK92tren thanhph~ncdbancuamallchut}t nhilt: Bang 3.34:Solu(/ngh6ngcdu(tri~uJmm3)tru(Jcvatrangquatrinhthitnghi~m 88 f, 86 li I(~ 8A I~ :...> I ~ 82 l 1<0 I ..:= 8f ~ I :s 78 !::. I- [ '<0 76 f C/j f 7A ~ i 72 l . Chang ~K92 TruocTN sau15ngay Thaidiem sau30ngay ffinh 3.28:Sosdnhso lu(/ngh6ngcducuachuQtnhdttru(Jc vaTrangquaTrinhthitnghi~m ChC'ph5mK92khanglamthayd6is6luc;5ngh6ngdu coy nghlath6ngke vdidQtinc~y95%sauu6ngthuoclientl,lC30ngay. Thaidim La chung La K92 T P <0,05 TruckTN 7.75:t1.26 7.91:t0.86 0,56 - Sauu6ng15ngay! 8.36:t0.47 8.55:t0.95 0,57 - i Sauu6ng30ngayi 8.05:t1.04 8.34:t 1.00 0,64 - 141 Bang3.35:56'll1(/ngbc;zchcdu(ngan/mm3)trl1acvatrangquatrinhthitnghi~m Soluqngbi,lchc~utrttocva sauTN -- 95 M ~ E 9 ........ c: '~ 85 c:'-" 00 8 c: E" ~ 75 . Chung: 1mK92 '<0 CI') 7 truoeTN 15ngay Ngay 30ngay I ffinh 3.29:Soll1(/ngbc;zchcducuachuQtnhdttrl1acvatrongquatrinhthitnghi~m Sauthtinghi<$m30ngaysoluqngb~chdu ca 2 16d6utang,nhu'ngsl,t khacbi~tgiua216khongcoynghiath6ngke. Thai dim L6 chung [ L6 K92 T P <0,05 TniocTN 8.17:t1.61I 8.03:t1.36 0,21 - Sailu6ng15ngay 8.06:t1.03I 8.07:t1.35 0,18 - Sailu6ng30ngay 9.23:t1.56I 9.37:t1.76 . 0,18 - 142 Bang 3.42: nl~%b(lchcdudanhantru:acvatrongquatrinhthil:nghi~m 42 --- 415 ,<~ :J ...c :J 41 II Chung: rnK92 ~o ..D * 405 r<C)o -- E= 40 395 TruoeTN sau15ngay Thaidi€m sau30ngay Flinh3.30:n l~% b(lchcdudanhancuachuQtnhdt truccvatrongquatrinhthitnghi~m Che'ph£mK92khonglamthayd6id 1<$b~chc~udanhancoynghIath6ng ke voi dQtinc~y95%sailu6ngthu6clien U;lC30ngay. Thai dim I La chung La K92 I T P<0,05,I TnI'ocTN 40,2:t4,55 40,8:t5,89 0,25 - Sail u6ng15ngay 41,6:t6,99 40,8:t5,98 0,28 - Sail u6ng30ngay 40,5:t7,02 41,0:t6,90 0,16 - 143 Bang 3.37:n l~% bq.ehedudannhantruaevatrangquatrinhthitnghi~m 60 i 595 l V') (]) 'p 585 ~.r!- §; 58 . Chung! ~K92 57 TruDeTN sau15ngay ThC1idi~m sau30ngay IDnh 3.31:171~%bq.ehedud(JflnhaneuaehuQtnhdt trUde1"iItrangquatrinhthitnghi~m Ch6ph~mK92 khanglamthayd6i ti lt$b~chc~uddnnhancoynghla thongke vdi dQtinc~y95%sailuongthu6clien tt,lC30ngay. ii l Thaidim La chung I La K92 T P <0,05 I TrudcTN 59,8:!:4,55 I 59,2:!:5,98 .0,25 - Sailu6ng15ngayI 58,0:!:7,35 i 59,2:!:5,97 0,40 - Sail u6ng30ngay 59,5:t7,06 I 59,0:t5,69 0,35 - 144 3.8.3.2.Khao satanhhu'dngcuaK92 tren chi 86sinhhoacd bancuamall chuQtnhiit: Bang 3.38:HamlLtlJ11gGPT (ALAT)tntoc vatrong.quatrinhthitnghi~m(UU) 70 60 t 50 0 ~ 40= ~.30 := :§ 20.... 10 0 II Chung 1mK92 T ruDeTN sau15ngay ThiJidiem sau30ngay Bang 3.32:HamlLtlJ11gGPT (AlAT) cuachuQtnhdt tntocvatrongquatdnhthitnghi~m(U/fl) Ch€ ph<fmK92khanglamthayd6ihamlu'<1ngGPT coy nghlath6ngke YDidQtinc~y95%sanu6ngthu6elien~e30ngay Thaidim La chung La K92 T P <0,05 TruDeTN 50,31:t4,50 48,23:t5,78 0,90 - Sanu6ng15ngay 55,40:t6,98 57,89:t6,90 0,80 - Sanu6ng30ngay 46,96:t6,79 48,09:t7,09 0,84 - 145 Bang3.39:HamlLl(JngGOT(ASAT)rntacvatrongquatrinhthitnghi~m(um) E-o 0 40 ~ ;:: 30-5 E 20,~ ::I: 60 50 i tI Chung: mlK92 10 0 TrtJocTN sau15ngay Thaidi~m sau30ngay Bang 3.33:HamlLl(JngGOT (ASAT)cuachuQtnhdt tntacvatTongquatrinhthitnghi~m(UII!) ch6 pha'mK92khanglamthayd6ihamluQngGOT co.ynghiath6ngke yoidQtinc~y95%sauu6ngthu6Clien t\1c30ngay Thaidim La chung La K92 T P <0,05 TntocTN 41,78+7,01 46,09:t5,67 1,51 - Sauu6ng15ngay 47,84:t8,09 50,56:t4,56 0,87 - Sauu6ng30ngay 56,58:t9,67 55,98:t7,89 0,18 - 146 Bang3.40:Hamlu(JngUre(mg%)mdutrU(1cvatrongqua'trinhthi/:nghi~m 14 135 <v .... ~ ~ 13 g S 125 ,~ ::I: . Chung mK92 12 115 TruceTN sau15ngay Th<'Jidi~m sau30ngay Hinh 3.34:Hamlu:qngUre(mg%)maucuachuQtnhdt tnMcvatrongqua'trinhthiinghi~m Ch€ phimK92khonglamthayd6ihamhiQngUrecoy nghIath6ngkevdi dQtinc~y95%sauu6ngthu6clientl;lc30ngay Ch€ phimK92khonglamthayd6ihamluQngUrecoy nghIath6ngkevdi dQtinc~y95%sauu6ngthu6clientl;lc30ngay Lo chung Lo K92 T P <0,05 Thaidi6m Tru'ocTN 13,26:t0,71 12,89:t0,67 1,19 - Sauu6ng15ngay 12,85:t0,52 12,30:t0,76 1,89 - Sauu6ng30ngay 13,71:to,92 13,87:t0,60 0,92 - 147 3.8.3.3.Khaosatanhhu'dngcuaK92trenems6sinhhoacdbancuanu'oc ti~uchuQtnhiit: Bang 3.41: pH nz({jeti!utntGeva trongquatrlnhthitnghi~m -~ 568 566 ~~ 564 :: 562 '8 C 56 :;.558 <c. ~ 556 554 552 --- i . II CJ:ung I . :1~K92 '---I I TruoeTN sau15ngay Thoidiem sau30ngay mnh 3.35:pH nz({jetiiuehuqtnhdtn({jevatrongquatrlnhthitnghi?ln Ch€ phcfmK92khanglamchayd6itrisO'pHnudeti6uCO:fnghIath6ngke vciaQtinC?y95%sauu6ngthu6clienWc30ngay. Bang3.42:Tl trr;mgnUGetiiu tnidevatrongquatrinhthitnghi?m Thaidi6m Lachung LaK92 'T P <0,05 TrudcTN 5,67:t0,61 5,57:t0,23 0,49 - Sauu6ng15ngay 5,60:t0,76 5,64:t0,34 0,15 - Sauu6ng30ngay 5,63:t0,54 5,57:t0,47 0,53 - Thaidi6m La chung La K92 T P <0,05 TrudcTN 1,024:t0,007 1,025:t0,005 0,3 - Sauu6ng15ngay 1,023:t0,006 1,022:t0,005 0,3 - Sauu6ng30ngay 1,025:t0.005 1,024:t0,006 0,3 - 148 Che'pha':mK92lu~onglamthayd6id trQngnuocti€u c6y nghlathongke VOldQtinc~y95%sailuongthuoclientl,Ic30ngay. K€t quakhaosatduongvaAlbumintrongnuocti€u chuQtnh~tsailkhi uongK92 15,30ngayla:amtinh. . Che'pha':mK92 VOl li~uthti'nghi~m0,2ml1kgth€ tn;mg, u6nglien tl,Ic trang30ngaykhonggay anhhuangc6ynghIath6ngke d6i VOlcactri sO'huy€t hQc,sinhh6agall, th~ncila chuQtnh~ttr~ngthi nghi~m.J:?i6ulJay chungtoche' pha':mK92 anlean,c6th€ sti'dlplgtrangdi6utri daingay. Tli c~ickGtquath1,1'cnghit%mcila chuong3, chungtoi c6 mQtsonh~nd:mh sail: 1) Khd niing lingd1:lngnghifmphdpBrodie vao linh VlfCnghiencztuchuyinh6a chdtIt;ltrangddu kifn Vift Nam: CochegiaidQcthongquah~th6ngenzymchuy€nh6aMonaoxygenaseIa mQfva."nd6davadangra."tduyccacnhanghiencti'usinhhQcquartam.Trong di~uki~nCJn thie'uth6nv6trangthi€t bi nhuVi~tNamhi~nnay,vi~cTIghten cuuffiQtchuyennganhSailnhuv~yconra."tnhi6ukh6khan.Chungtoidfiapd~mg nghi~ffiphapAntipyrin- mQtphuongphaptuongd6i don gian,phuhQpVOldi€u ki~nkinht€, ky thu~thi~ncovabuocd~uthuduQcnhungk€t quanghiencuu. dangtinc~y. PhuongphapBrodie dUngAntipyrin lam cha."tchi thi mall d€ danhgia tr~ngthaidQnghQccilas1,1'thairrUvatr~ngthaidQnghQccilacacenzymxuclac 51,1'chuy€nh6acuavi ti€u th€ gall(Stevenson1977),d1,1'atrencosaphanU'ngsinh hoahQcdi€n ratrangcoth€ theaphuongtrinhduoiday: , ~CH3 0 6 '" if N"", CH3 I~ ~ Antipyrin 149 HO :ex: CH3 Hydroxl'ase - Monooxygenase 0 ifN"", ., 0 CH3 4-hydroxyantipyrin PhftnAntipyrinconI(,!.i!TongmatiseduQcxacdinhquaphanlingmfmvoi HNO2rheaphanling: r=:==-!CH3 o 6 lif~"'" CH3 I~ ~ Antipyrin /-;;,>/02. NO~CH3 0l. /~' 6 ifN"", CH3 I~ ~ 4-nitrosoantipyrin Sanph:lm4-nitrosoAntipyrinco matixanhngQc,se du'QcdinhIuQngb~ng phuongphapdoquang.M~tdoquangcuachitnaynIt$thu~nvoin6ngdQ,day1a . . mQtdftnsuit phananh ham 1uQngAntipyrin th1,1'c,kh6ngbaa g6m bit cli san ph:lm chuy~nhoa naGkhac, kh6ngbi can tra bai cac chit khac, ngo(,!.itrU suifadiazin(B.H.Phlicvacs. 1990). Ke'tquath1,1'cnghit$mchodUlY:nghit$mphapAntipyrinquath1,1'ccogiatritren d6i tu'QngnghienCUumoi Ia chuQtnhcltrclng,vi nhii'ngIf dosail: a) Voi maydoquangSECOMAM S-750,chungt6i dffxac dinhdU<;1Cbuoc songhip thu c1,1'cdai cua 4-nitrosoAntipyrin (san ph:lm cua IU<;1ng Antipyrincon l(,!.itrongmall chuQt)ke'thQpvoi Natri nitrit trongmoi truongacid Sulfuric. Tli do, chQnbuoc song 345nmlam bUGCsong thichh<;1ptrongcac thli'nghit$mtie'pthee.Bay la buoc songdodu<;1c 150 trenh~uh€t cacmaydoquanghi<$ncot?i cacphongthinghi<$mVi<$t Nam,chonenvi<$ctri~nkhaiapd\lngsed€ dangbon. b) Cacy€u t61yboacuamoitntongkhfh~utl!nhienanhhudngror<$td€n k€t quath1,I'cnghi<$m,nhu'ngkhongphailakhongkha:cpht;lcduQc:m~u chu:1nAntipyrinn6ngdQ1% coth~baaqUailtrong15ngay;thu6cilia NatrinitritlamQthoach!td~bioxyhoa,nhungn€u d~trongchaithuy tinhmallnau,nutkinthlclingchok€t quatinc~ytrongvonglOngay. SodIchungtoichQn hi<$tdQ:.baoqUaillanhi<$td~phongbinhthuong, VIkhongphait!t cacaephongthinghi<$mhi<$nnayd~uduQctrangbi mayI?nhtieuchuffn.bellc?nhdo,tlnhtr?ngm!tdi<$nd(?txu!tclingco xay fa, thoiquellngfttdi<$ncu6i gio lam vi<$c...se lam inh huangd€n ch!t luQngch!t chu:ln\-athu6crbii'.K€t quakhaosatdQb~ncuacac hoach!t thamgiaphanlingchoth!y nghi<$mphapAntipyrincokha nclngling d\lng rQngrii aVi<$tNam,khongchi a nhungphongthi nghi<$mtieu chuffnrna con sii' d\lng duQccho ca.nhungphongthi nghi<$mlUlldQng,VIcaely do:hoach!t dongian,d€ tlm;di€u ki<$nbaa qUailkhongquang~tngheo;khongc~nphaiphathu6ctham6ingay. c) PhuongtrlnhduongchulnAntipyrin(Ct =Et x 0,034 + 0,0107)co h<$s6tuong quail (R =0,9998)r!t ch~tche,lamQtcongct;ldangtinc~y dungd~xacdinhn6ngdQch!t thii'theom~tdQquang.Bliongchu:1n tuy€n tinhtrongkhoangn6ngdQkhaosat:0,5- 20~g/mlvdi saisO' ch!p nh~nduQc.Dt;1'aVaGphuongtrlnhnaysexacdinhmQtcachnhanh chongn6ngdQAntipyrintrongcacthii'nghi<$mkhaosattu'ongmccua cach<Jpch!tthiennhienmangho?ttinhsinhhQcvdiHydroxylasecua h<$enzym chuy~nhoa. 151 d) Voi lieu luqngAntipyrinduavaGco th~chuQtnhiitla lOmglkgth~ trQng,chungtoichQndu<;1CthaigianIffymatichuQtla:30phut,1gia30 phut,3gia,5gia.T:p.cacthaidi~mnay,n6ngdQAntipyrinn~mtrong c, gioih';lntuy€'ntinhvad6thibi~udi~ntuongquailgiualogariritn6ng dQvoi thaigianla IDQtduangth~ngdi xu6ng,thu~nlqi chovi~ctinh roanthaigianbanphanbuycuathu6c.K€'t quathl,icnghi~mchothffy: cacthaidi~mdachQnphuhqpydi yeticftuthanghi~mvad6ituqng moidungtrongnghiencoo. e) DQnh';lycuaphuongti~ndoquanghi~nco chophepsa dvngcacm~u thii'co th~rich,n6ngdQkhiLnho(tu0,5Jlg/ml),phuhqpvoi th~tich matiIffyduqctrenchuQtnh~h,lo';lisucv~tcotrQnglu<;1ngcoth~nho, tu6ithQngiin,t6cdQchuy~nhoanhanh. f) Vit$cxacdinhduqcn6ngdQAntipyrinconl';litrongmatichuQtsegiup sur ra t6cdQchuycfnhoaAntipyrin,nhodo danhgia duqcho';ltdQ enzymHydroxylase- IDQtenzymchuy€'ucuah~Monooxygenase. g) D~dambaadQdungcUaphuongphap,chungtoidasad1:mg2chfftd6i chti'nglaPhenobarbiral(PB)vahqpchfftSaponintriterpenchi€txufftU SamVi~tNam(SVN).PBlamQtchfftcamti'ngenzymchuy~nhoakinh di~n,vi tri tuongtact:P.52KDa,hftuh€'t cacthii'nghit$mkhaosatkha nangtuongtacenzymdeliIffyPB lamchfftd6ichti'ng.HqpchfftM.R2 vah6nhqpSaponintoanphftntrongSVN cfingla mQtcffutrUcdaduqc c6ngb6vekhanangtIl'dngtacvoiCytochromP-450t';livi tri57va54 KDa [51],[52],[53].Trennghi~mphapAntipyrin,caPB vaSVNdeli th~hit$ntacdvngc:imti'ngenzymHydroxylase,thucd§yquatrlnh hydroxyhoaAntipyrinITathanh4-HydroxyAntipyrin.Dieunayduqc th~hit$nquatacdl,mgnitngiinthaigianbanphanhuyAntipyrinvalam_. 152 gia tangra r<%ttrQngluQnggallchuQt.Ktt quathuduQctutht,tcnghi<%m dffchungminh dQtinc~ycuanghi<%mphapAntipyrin va la cd sa d€ chungtoiapdl:mg;nghi~mphapnaytrongcackhaosattitptheo. Cac ktt quathl,tcnghi~mmota trongph~n3.1cho tha"yvi<%capdl:mg nghi~mphap Antipyrin trend6i tu'QngnghienCUumdi - chuQtnhfttclng- la hoanroancocdsakhoahQcvacogiahi tht,tcti8n. 2) TinhquylugtsinhhQccuacaecaythu5ctronghQAraliaceae: Cacnhatht,tcv~thQccanctyVaGh1J.hthaigiai ph~ude phanlo~icayco,xtp caccaycod?cdi€m v~hinhthaivagiaiph~ugi6ngnhauVaGmQthQtht,tcv~t. Khiphanrichthanhph.1nhoahQc,nguoital~itha"yr~ngh~uhtt caccaythuQchQ Nhansam(Araliaceae)d~uco chua~1QPcha"tSaponin(ph~l~c1),trongdo Saponintriterpenla ho~tcha"tchinhth€ hi<%nLaCd~ngsinhhQCchuytu cilahQ nay.Theo cacnghiencUumaidaytren60 m~uduQcli<%uthuQc25 loai tronghQ Araliaceaed?chl1ut~iVi<%tNam.cacnhakhoahQccilaTrung tamSamvaDuQc li<%uTPHCM clingd1,1'aV Gquylu~thoatht,tcv~td€ t~ptrungtimkitm hQpcha"t Saponintrongrn~urndiphathi~n.Ktt quaphandchsobQchotha"yhQdffill dung huang,trong60rn~uduQcphanrich,co45rn~uth€ hi<%ns1,1'co m?tcilahQpcha"t Saponinva hQpcha"tnay chitmti l~chliytu trongthanhph~nho~tcha"ttrongca la,than,r8.Ngoaifa,conco14m~unghingacoSaponin[166]. Theokinhnghi<%msad~ngc:1yconlamthu6ctUthaic6d~idtnnay,caccay thu6ctronghQAraliaceaeduQcxtpVaGlo~ithu6cb6duong,chilytu lanhomb6 khi.Nhansam,Tamtha"t,Binhlang,Ngligiabi duQccoi la nhungvi thu6cquy, DangcaDkhaDangd~khang,ch6ngdob<%nht~tcilaco th€, dunghi cacchung suynhuQctinhth~nva th€ ch{~anngukern,datinh(tcxu'ongkhap,cacb~nh ffiq.ntinh...Xua,nhungnguaiill rungthuongng~rnvai lat samd€ khongdn an u6ngmav~ncosuckhoedivaingayduong.Th~rnchi,vdinhungnguaigiaytu, L , 153 khis~plla doi,duejcnguoinhachong~msamd~dejiconchau(jxa v~g~pm~t. Nay,succhilidt;tngdeodaicuacacv~ndQngviendi~nkinhHanQu6c,Trung Qu6cmQtph~ndu<;1ccho Ia hQdadu<;1csa dl~ngcacIo<;linudcu6ngche'bie'ntit Nhan sam.Cac thanhvien cuadoandu hanhvii tn,INga (Lien xo cii) dii dung samtrongsu6tcuQcduhanhkh6nggian.Khaosattacdl.fngch6ngm~tmoivdi nhunghQIy tn1ccadem(jb~nhvi~nchotha"y:nguoidungNhansamcamtha"yit m~thdn,tinhcanhgiaccaDvanangdQnghdnso vdi nh6mkhongdungsam (FuiderS.) Ke'tquanghienCUlltittrudcdtnnaychotha"ycotinhquyIu~tv~v~tacdl.fng sinhhQccuacacdu<;1cli~uhQA.raliacea:tangh1c,ch6ngstress,tangkhanang sinhthichnghi,khangviem,giamdati,giai dQc,h6 tr<;1trongdi~utri IaudaimQt sO'b~nh(ti~uduong,timm<;lch.ungthu...)...Vi khongdu<;1ccoi Ia mQtthu6cd~c trt,Nhansamcom~trongkhanhi~ubaithu6cb6,sad\:mgsailgiaido<;lndi~utri ta"ncong,ho~ctrongcacb~nhID.<;lnti hnhamml.fCdichchuye'uIa nangdoth~ tr<;lngbi saynhu<;1c,d6cdth6tt;tcliy Iui b~nht~t.Ngaynay,clingvdi cactacdl.fng di~utq noi tren,Nhansamdu<;1ccoiIa mQtdu<;1cli~uco tacdl;lngantioxydant. CacnghienCUllsanglQcmoidaycuaTrungtamSamvaDu<;1cli~uTP HCM trentacdl.fngtangIt;1'c,h6ngstresstht;1'cnghi~m,dii clingcO'themnh~ndinhv~ tinhquylu~tsinhhQcnay.Khaosattren2mohlnhchuQtbdiki~tsucBrekhman (lg - 2g1kg)va stressn6ng(200mgJkg)chotha"y:co 25/34mftuth~hi~ntacdl.fng tangIt;1'c(76,5%mftuilia), trongdo18/34mftud<;ltynghlath6ngke;8/34mftuilia th6hi~ncatacdl.fngtangIt;1'cvaantistress(32%mftutha),chuye'uIa cacmftu du<;1cli~u thuQcchi Panax, Schejjlera,Acanthopanax,Polyscias,Macropanax, Aralia, Trevesia(phl.fIl.fc2). Ktt h<;1pvoi ktt quadinhtinhbangphudngphats~c kYlOpmong,cactacgiadiikh~ngdinhvaitrolienquailcuaSaponinvoicactac dl.fngsinhhQcdi6nhinhcuahQ:'-ThansamIa:28phando<;lnSaponinroanph~n 154 cua cac m~uco taGdl:mgtanglvc ci€u th6hic$ncacve'tco mall s~ctUongtVcac m~uci6ichlingcuasamTri€u Tien,SamVic$tNam,Binhlang [166]. TheoGongb6cuaKuongpD. 1989,hQpcha'"tM.R2 vah6nhQpSaponinroan ph~nchie'tur~ciiyPanaxviemamensisHaetGrushv.tuongtaGvoiCytochrom P-450t~ivi triproteinco trQngluQngphantu57va 54KDa, quadolamtang hamluQngCytochromP-450(160%),giamt6cdQphanlingoxyhoaAnilin(55% va44%),Amidopyrin(61%va49%);Dcche'g~nnhuhoanroanst;1'oxyhoaacid bee khongno (96%).B~cOic$(khanangantioxydantcua h6n hQpSaponin triterpenm~nhhondoncha'"tM.R2 [51],[52],[53].Tren invivo,Tam tha'"tco taG dl:mgantioxydant[132];SamLie;}xokhi dungchungvoi mQtsO'tanduQccialam thayd6itaGdl;mgcuachung[119]. Ne'uhQAraliaceaedamangtinhquylu~tv€ d~cdi6mtht;1'cv~t,thanhph~n hoahQc,taGdl:mgduQcly, lic$ude caytronghQnayco tinhquy lu~tv€ khanang camlingenzymchuy6nhoathuockhong? Phantichcacke'tquathunh~nt:Utht;1'cnghic$m,chungtoi co nh~nxet:4 m~u duQclic$ukhaosat(Nhansam.Binh lang,Tam tha'"t,Ngfi gia bi chanchim)d€u gaycamlingenzymMonooxygeilasetrenchuQtnh~tdng,th6hic$nquataed~ng lamtangt6cdQphanlinghydroxyhoa,rutng~nthaigianbanhuycuaAntipyrin, d6ngthaigiatangtrQngluQnggallehuQtnh~t.Tht;1'cnghic$mduQctie'nhanhtrong cungdi€u kic$nsongsongvoi 2h<;1pcha'"tcamling enzymdi6nhinhcoca'"utrUCva dQtinhkhie'tkhacnhaula Phenobarbitalvah6nhQpSaponinchie'tUSamVic$t Nam.Ke'tquatrinhbaytrongbang3.12chotha'"ythaigianbanhuyAntipyrincua cac10thli'la76,23- 87,50phut(giam23- 33%sovoi chling).B~thic$uqua38- 55%sovoi PhenBarbital(80mg/ kg)va63,4- 91% so voi Sam Vic$tflamkhi sli' d~ngcungmQtli€u 20gduQcli~ukho/ kg chuQt.Ke'tquabang3.13chotha'"yst;1' 155 ", gia tangtrQngh1Qngall chuQtcila410thii'tu12,5- 14,1%, tudngtVvai10chuQt u6ngSamVi<$tNam(15,32%)vaPhenobarbital(19,15%). Cac ke'tquaphftn3.3cia,chUngto rang4 mftuduQc1i<$utieubi~ucuahQ Araliaceaemachungtoi nghienc~"Uco d~cdi~mchungv~khanangearnung enzyrnchuy~nboa.Bay Ia cdsabandftucoth~nh~ndinhthemmQtmhquylu~t sinhhQcmaicilahQAraliaceae- quylu~tthamgia tudngtaGvai h<$enzym Monooxygenase,thongquadothJ hi<$ntaGd\:mg iai dQc,di~uboanQimoi. 3) Khdndnglingdlfngcila chi pMm K92: K92 g6m8vi thu6ctheeGongthUGcuabaithu6cc6truy~nB6Trung1chKhi. Nh:imml,lcGichthuGuQchftuhetho'.ltchfttanduQctrongdungmoikhongphan c1,1'cva dungmoiphanqtc, chUngtoi apdl,lngphudngphapchie'txuatngarnki<$t giamdftnGQc6nke'thQpvai phuungphapc6 truy~n- sacvainuac- d~duQch6n hQpcaolongc6n- nuac(KuongD.D.d~nghi) ChungtoiGaxacdinhti trQng.GQc6n,hamluQngSaponinloanph~ncilaK92 d~Himcdsalieuchu~nhoasanph~msailnay(phftn3.8.1).B~ki~mtratinhan loancuache'ph~m,chungtoichochuQtnhatu6ngK92lientl,lctrong1thi'ng,ke't qua.xetnghi<$mchothftyK92kh6nglamthayd6icactris6mau,chu'cnanggall, th~ncuachuQthingm<$m(phftn3.8.3).Bay la mQtrongcacdi~uki~ncftnthie't (theoquydinhcuaBQY te'Vi<$tflam)tru'ackill duamQtche'ph~mcongu6ng6c tVnmenVaGthii'ngm<$mlamsang. Khi thii'trennghi<$mphapAntipyrin,che'ph~mK92 dath~hi<$nlac d\:lllggia tangv~nt6cphanunghydroxyboa,rutnganthaigianbanbuyAntipyrincon 64%, giatang11,7%trQngluQngallchuQt.Tacdl,lngnaycuaK92tudngt1,1'nhu 2 G6ichungPhenobarbitalvaSamVi<$tNam.M~cdlihamluQngSaponinNhan samtrongche'ph~mK92nhohdn10lftn,nhungvftngayGuQchi<$uungtu'dngtV nhukhi sii'dl,lngNhansamdQcvi.Trongkill do,d 10chuQtu6ngh6nhQp7thanh 156 ph~nconl~icuab~liBTIK (K92khongNhansam)cothaigianbanbuy(bang 3.15)vatrQngluejnggall(3.16)tu'dngtv10chung(chuQtblnhthu'ang).Chungto lacd~ngcamungenzymcuafhephffmK92la docachejpch(tSaponintriterpen cuaNhansam. Di€u gl dat~onenhi~ulingtu'dngtva nhii'ngli€u luejngSaponinkhacnhau khaxanhu'v~y?Khi matrongthl1ctes11d~ngthu6cv6nconhii'ngquydinhch~t chev€ li€u luejng?!!D~tralai callhoinay,c~ntiept~cconhii'ngkhaosatlo~i trutrongtUdnglai.Theochungwi tienli~uthldaycoth6la lacd~ngtu'dngh6 cuacacthanhph~ntrongbitithu6cd~nangcaohi~uquadi€u ttimaDongy gQi la "tu'dngsa"- cacvi thu6ckhacnhau,ld1is11d~ngchungselamtanghi~u111c cuanhau.Ho~cclinggiathietmea19lu;~ndungthu6ccuaDongy 1:1l(y "khi" lamchinh- h~uhercacvi thuocc6truy€nco khoangli€u lu'ejngkharQng:4- 16g,8-20g...[129],[175].Ma Nhansamla mQtvi thu6cb6khi,khisad~ngdQcvi thu'ang1:1ng~m,ho:)chamd6gillla'yph~n"khi"cuavi thu6c. Khi s11d~ngchungvoi mQtsoduejcph~mtrencacmo hinhb~nh19thvc nghi~m,K921amtanglacdl,mgcilanhungc(a tnichoahQcr(t khacnhau: Voi Morphinli€u 5mg/ kg(nhanPhenanthrenvaPyridin),K92 lamtang lacd~ng iamdati1,461~n[145]. Voi Paracetamolli€u 300mg/ kg (dftnxu(t Anilin), K92 lamtangtaG d~ngh~s6t 5,5- 11,2lfuLtangtaGd~nggiamdati1,47lin, keGdaithai gianlacd~ng30phut. Voi Insulin li€u 1VI/kg (ca'utrUcpolypeptid),K92 lam tanglac d1,1Ilgh~ duangbuyer1,38- 1,51lh. Tac d~ngnay th~hi~nsail20phutvaduytrl trongtrangsu6tthaigiantheod6icuamohlnhgaytangdu'anghuyet.Lo sadl,mgK92chungvoiInsulindu'adu'angbuyertumUG400mg%trav€ gioih~nblnhthu'angsail40- 90phutsad~ngthuoc.T~ithaidi6m40va 157 60 phuts1,1'khacbit$tv~n6ngdQglucosetrangmallchuQtgiii'a2 10dung K92k€t hQpInsulinva10cmdungInsulinkhacbit$tco'1nghIath6ngke, chungtovaltraxuctaGcUaK92., D~cbit$tkhi ph6ihQpvoimQth6nhQpduQclit$u(bai thu6cNamh'J.duang huy€t), ch€ phim K92 clinglamthayd6i taGd\Ingh'J.duanghuy€t cuabai thu6c,mara tri€n vQngmoitrongph6ich€ nhflmnangcaohit$ul1!ccua thu6cY hQcc6truy~n.Cin ti€p t\ICkhaosatd€ xacdjnhtu'ongtaGcua K92d6iVOl.thanhph~naotrangbatth?6cg6m2duQclit$uKh6quavala Danay. Morphin,Paracetamolc1uQccongnh~nla nhii'nghQpchcftchuy€nhoaqua microsomeegall.K€t quatrongph~n3.5chothcfyK92cokhananglamtang taGd\:mgduQc1'1chuyenbi~trencachoachcftcoccfutrucphantakhacnhau: vangdon,vangeta,polypeptid.Do chuaco nhii'ngnghienCUllSailv~ham luQngho'J.tchcftv~nchuy€nquamangt€ baa,nenchungtoid~tgiathi€tday lakhananghinhthanhcacchathoahQctronggallcuaK92. NghienCUllkha nangcarnlingenzymd€ iiai dQccuaK92chungtoinh~n thcfy: TrenchuQtnh:ltbi chi€uCosoroanthan(1i~uSOy),cacchisO'huy6thQc: h6ng c~u,ti€u c~u,b'J.chdu beltdati giam ngay sail khi chi€u X'J.1 ngay va khongt1!h6iph\Icsail28ngaytheedol.Trangdo,sO'luQngti€u c~ugiamro nhcft,sailchi€u X'J.3 - 28ngaychi cankhoang37- 46%so voi trUockhi chi€u X'J.va so VOlchuQtblnhthuang.s6 luQngb'J.chc~ucfinggiamm'J.nh trongkhoang3 - 14ngaysailchi€u X'J.,can khoang25 - 60%.K€t quath1!c nghit$mnayphuhQpVOlGongb6cuaNguy~nXuanPhachvacQngs1,1'v~anh huangcuaphongX'J.trenthanhph~nhuy€t du cuachuQtnh:lt[156].0 10 chuQtduQcdi~utri bflngK92 s6 1uQngh6ngc~u,b'J.chc~u,ti€u du cfing 158 gram,nhungba:td~uh6iphl,lcsail7 ngayva co khuynhhuangtrdv~blnh thuangsail28ngaydi~utrioD~cbi<$t,s\fkhacbi<$tv~t6cdQgramti<5uc~u cua16chuQtu6ngK92va16kh6ngdi~utrinit co y nghla:tt;!ithaidi<5mti<5u c~ugrammt;!nhnh1tdophongxt;!thlK92lt;!icolacd\!ngr6r<$tnh1t. Khi khaosatlacd\!nggayngucuaBarbitaltrenchuQtnhi~mxt;!,chungt6i th1ythaigianngucuachuQtang2,25- 3,9l~nso vai chuQtblnhthuang trongclingdi~uki<$n.Trangkhido,thaigranngucua16chuQtduQcdi~utri b~ngK92 vaSVN It;!itU'ongtV16chuQtkh6ngbi chie'uxt;!.Cac thu6cngulot;!i Barbituricchuy~nhoa qua microsomegall, duOianh huang cua phongxt;!, chUGnanggallsuygram,lamchokhanangchuy<5nhoathu6ccuagallclingbi ?nhhuang.Khi h<$enzymchuy~nhoatt;!igallkh6nglamtronnhi<$mV\!,thl Barbiturichill giutrongcoth~lauhonblnhthuang,ke'tquaIa thaigianlac dl,lngcuathu6cnguBarbituricbikeodaihonblnhthuang.Tren16chuQtchie'u xt;!va di~utri b~ngK92,giacnguBarbituricchi bi keodai 1,8l~ntt;!ithai di<5m10ngaysailchie'uxt;!,chungtotrongkhoangthaigrannayh<$enzym chuy<5nhoaconchinanhhudngcuaphongXt;!.Nhunga nhungthaidi~msail, anhhuangcuaphongxt;!lIengi1cnguBarbiturich~unhukh6ngconQua.Ne'u- ke'thQpthai granngu Barbiturricvai ke'tquahuye'thQCthl co nhi~utuong hQp:sail 14ngay,noi chungcactri s6 huye'thQcd~ugia tangco y nghlaso VOl16kh6ngdi~utri,nh1tIII s6luQngti<5uc~uluGnay dfftrdv6 giai ht;!nblnh thuang. Cac th\fcnghi<$mph~n3.3,3.4va 3.5cho th1yhQpch1tSaponincuacac cay trong hQ Nhan sam va cua che'ph:fmK92 dff tuong lac VOlenzym Hydroxylase,quadocamungh<$enzymnay,lamtangt6cdQchuy~nhoach1t. It;!,trongdocophongxt;!vaBarbituric,quado,lamgramvam1tdQctfnhcua chung. 159 Dt!aVaGcacsoli<$uthudu'<;1Ctuthvcnghi<$mtrongphftn3.6.1,chUngtai co th€ kh~ngGinntaGdl;lngbaav<$phongx~GuaK92 trencact6nthu'dnghuye't hqcvachuGnangchuy€nh~acuaht$enzymgall. ChuGnangho~tdQngcuagall du'<;1cdanhgia dva VaGcaechuenang,. chuy€n hoa (glucid,lipid...)va cac roi lo~nenzymdo t6n thu'dngt6 chue. SGPT (Serumglutamicpyruvictransaminase)haycongQila ALAT (Alanin aminotransferase)khutnichuye'utrongnguyensinhchit te'baagall,khico hi<$ntu'<;1ngtieuhuyte'baagalltill enzymnaytangcaDtrongmati.TrenchUQt gaydQcgallb~ngTetracloruacarbon(CC14),hamlu'<;1ngGPT huye'thanhtang gip 2,1-2,6 Iftnchungtocohi<$ntu'<;1ngfillYho~ite'baanhumagallvat6n thu'dngallv~ncontie'pdi~nde'n gayrhead5icuoieuathinghi<$m(ngaythu 7)(bang3.27).vdi16chuNau'<;1Cdi6utrib~ngK92,GPT tangit varIav6gidi h~nblnhthu'ongsau7ngay,chungtohi<$ntuQnghuyho~ite'baagallill giam sovdi 16gaydQckhangdi6utrio Ban thanTetracloruaearbonkhangco dQclinn,ma sanph~mchuy€nhoa cuanomdicodQctinh.TaedQng ayho~itagallcuaTetracloruacarbondu'<Jc giaithiGhquadayphanungphongthiGhgoctVdosauday: . CacgoetVdodu'<JcphongthiGhrheadayphanungtrenla taGnhangayt6n thu'dngnhumagall,s11giatangenzymchuy€namin(GPT)huye'tthanhlamQt trongcaediu hi<$uchothiy mUGdQt6nthu'dngall. Ham lu'<;1ngCytochromPA50 khi tangse lam giamlien ke'tgiuaCC14va CytochromP-450d€ nhanhchongciaothaiCC14ra ngoai[51],[52],[53]. CC14* -7 * cl*CC13 + CC13 * -7 * cl*CC12 + CCh * -7 ccl* + Cl* 160 Cac chit camlingh<%enzymMonooxygenaselamtangsinhh<%nayvaqua do thucdffyquatrlnhloC;!ig6ctVdo cl*, hi<%nnaynguoita thuonggQila mc dl,mgantioxydant.K€t quathltcnghi<%mcua-chungtoi rit phil h<Jpvdinhung nghiencU'uv~lac dl;mgantioxydantcuacaccay tronghQAraliaceaedacong b6trongcactaili<%ukhac[51],[52],[53],[76],[86]. f)~clingc6nh~ndinhv~khananggiaidQccuah<Jpcha'tK92,chUngtoi th6ngke ty 1<%chuQtch€t trongnhomchuQtdii gaydatib~ngacidAceticu6ng Paracetamol.K€t qua cho thiy: s6 chuQtch€t sau tha nghi<%mla 13/18 (72,22%),trongkhi do,n€u chochuQtu6ngthemK92, tmbell cC;!nhkhanang gia tang lac dl:mggiam daticua Paracetamol,trongyang 6 ngay sau thi nghi<%mkhongco chuQtchet(bang3.26).Giai thfchv~hi<%nt1i<JngchuQtch€t rai racsauthinghi~m,chungr6ichorangdayla dotudnglac giuaacidAcetic vdi Paracetamol,anhhuangdenkhanangAcetyl boa.Tha nghi<%mtrenchuQt nh~tcho thiy t€ baa th~nkha Acetyl cua Paracetamolchuy~nthanhp- aminophenol(mQtchitdQcvdith~n)dochuy~nhoathanhNAPQI [162].Sau do,chlicaminb~cnhit nayselienh<JpvdiacidAcetictc;!osanphffmaceto- h<Jp,it tantronglipid.d€ thaitrUquath~nvaquam~tvahetdQC.K92lachit camlingenzymchuy~nboa,thucdffyquatrlnhAcetylboa,kh~cphlJ,cdu<Jc nhu<Jcdi~mcua Paracetamol,nhodo nen giamtY l~ chuQtch6tsauthf nghi<%mdodQctinhph6ihQpcuaParacetamolvdi acidAcetictrenth~nva gall. Cackhaosatv~anhhuangcuaK92d6ivdicaclacnhan:phongxc;!,CC4, Paracetamoldii chungminhthemffiQtung dlJ,ngcua h<Jpchit Saponin triterpen,dola tacd~ng iaidQc. 161 Chungt6iclingda:khaosatanhhuangcilacacSaponinNhansamd6ivoi enzymchuy~nh6athongquatacdl;lngduQc19chuyenbi~tcila Cadellva Morphintrenmohlnhgay,hovagaydatitht!cnghi~m. CadeinvaMorphinla2 alkaloidthu6cphit$n,c6ciu tnicg:lngi6ngnhau, chikhacmQtnh6mchlicd carbonsO'3 (Codeinla nh6m metyl,Marphinla nh6m-OR phenol),chinhst!khacbi~tv6ciu trucnaymataedl;lngduQc19 chilyS'ucilachungkhacnhau:Codeingiamhom~nh,Morphinla mQthu6c giamdatikham~nh.Rai alkaloidnayd6uchuy~nh6aquagall,dangthai CodeinclingduQch~enzymgallchuy~nh6athanhMorphin.Trangdi6uki~n binhthuang,10%Cad~inbi O-demetyld~thanhMorphintrongco th~[136]. Tac giaNguy~nTr:ln GiangHuong-1997da:ling dl;lngd~~ctinh nayd~khao satcochS'taGdQngcilaArtesunatrenenzymchuy~nh6a [155].Khi ki~mITa mohinhvoi chit d6i chungPhenobarbital,chungtoi tha'yr~ngtrenchuQt duQcearnlingb~ngPhenobarbital,taGdl;lngucchS'conhocilaCadellgiam 25,83%,taGdl;lngtic chS'condatiqu~nbl;lngcila Morphin giam56,44%.KS't quanay tu'onghQpvoi 19thuyS'tv6 taGdl;lngcila chit ho~thoa enzymkinh di~n:Phenobarbitalam tangt6cdQchuy~nboa, tangthai tnI, quad6giam taGdl;lngcilaMorphinva Cadein. TiS'nhanhthanghi~mvoiK92,kS'tquathuduQcclingtheechi6uhuang tu'ongt1!: Voi Cadein:taGdl;lnguc chS'ho giam20,85%,taGdl;lnglie chS'dati tang 190%.Di6u nayclIo thiy cohon 10%CodeinduQcoxy hoaO-demetyld~ chuy~nthanhMorphintrongcoth~,dodokhanangticchS'hogiam,kha nangucchS'datitang[142]. Voi Marphin:taGdl;lngticchS'dati.chI giamkhoang9,96%.Trangcdth~ s6ng,Morphinbi chuy~nh6athongquaqua trinhN-demetylva glucura 162 h<jpd mierosomeeegalld<iehoMorphin-3-monoglueuronidma'tho~ttinh va Morphin-6-monoglucuronidv~ncon tae dl;lng[136], [155].KGt qua th1!enghit$mehoth1ycokhanangK92earnunglamtangsinhenzymxue taephanunglienh<jp,tangt~osanphffmMorphin-6-monoglueuronid,VI v~ymamedl;lng iamdaticuaMorphinchigiamehutit (hlnh3.36)[142]. CjtP-450. demetyl CH3 I N / OH Codein Morphin I ~ GlucuronidGlucuronid OH M orphi n-3 -m onoglu cu ran id Morphin-6-m 0noglucuTonid IDnh 3.36: Chuyinh6acuaCodein vaMorphintrongc(]thi £)~chungminhvaitrokfchhQatenzymcuaSaponinNhansamtrongchG phffmK92,chungtoitiGnhanhkhaosattu'ongtaccuaCodeinvaMorphinvdi K92, Nhansam,K92 khongNhansamtrenmo hlnhgay datibangacid . 163 Acetic.K{tquath1,icnghi~mchoth!ys6candaticua16chuQtkh6nggaycam lingenzymva16sii'd\mgK92kh6ngNhan~amtu'angduangMail, cost!khae bi~tdangk~vdi so'candaueua16chuQtearnlingb~ngK92vaNhftnsam. Trongdo,Codeingiatang23%tacd~nggiamdati,conMorphin1~ibigiam 18%tacd~ng. Tht!cnghi~mnay gapphftnclingco'nh~ndinhv€ khanangDehho~t enzymehuy~nhoacuathanhphftnSaponincuaNhansamtrongehe'ph~m K92,mynhien,d~lamsangtov!n d€ naye.1nphaidinhluQnghamluQng Codein,Morphinva caedclnch!teuachungtrongcoth~.Chungt6isetie'p t~cnghiencUuSailhall. Khi sos:inhanhhudngcuaPhenobarbitalvaK92trentaed~ng iamdati cuaCodein.,chungtoi th!yPhenobarbitallam giamtacd~ngcuaCodein, trongkhi l~iK92 lamtangmcd~ngnaycuaCodein.f)~giai thichs1;1'trai nguQcnay,chungtoinghIde'nkhanangtu'angtaccuacacthanhph.1nconl~i trongK92vdiSaponinNhansamvagiuachungvdiMail. Trongcaenghien CUutie'pthea,c.1ntachriengtUngthanhph.1nduQcli~ud~tlmhi~um6itu'ang taccuachung. Ke'tquanghiencoov€ taed~ngiamdaucuaMorphintrongbang3.26va 3.40tho~tnhillco ve nguQenhau:d bang3.26s6candaucua10ehuQtsii', d~ngd6ngthaiMorphinvaK92it hankhi chi dungMorphin[145];cond bang3.31va3.32thls6lftnqu~nb~ngcuaehuQtgaycamlingb~ngK92t~i nhi€u han10chidungMorphin[145].St!khacnhaunaycoIe tadothayd6i cachsii'd~ngcuaK92 trenmohlnh.Khi co di€u ki~ndinhluQngMorphin, Codeincungcacsanph~mchuy~nhoacuachungthlv!nd€ naysesangto. Trangdi€u ki~nhip thublnhthuang,chi co 1%li€u dungMorphinqua duQchangraGth.1nkinhtrungliang,giinvdi cacreceptord~chi~ud~gay J 164 ho~tinhgiamdati[136].Vi ehuacodi~ukic$nxacdinhcaesanph5mehuy~n hoacuaMorphin,lienchungtoigiathuy€tding:khisii'd~ngmQtl~nMorphin clinglucvdiK92,Saponin.Nhansamlamtangt6cdQv~nchuy~nMorphin quahangraGth~nkinhtrungudng,vi v~yconhi~uhdn1%Mprphing~nk€t vdi receptord~chic$u,nhadomaho~tIt!egiamdatigiatang.CankhiK92 du'<;1esii'dl:mgtru'delien ti€p trong3 ngay,SaponinNhansamdongvaitra tangsinhisoformenzymchuy~nboa,lienlamtangnguonggiamdati,dftnd€n lamgiamtacd~nguech€ daticuaMorphin.l:)i~un~yphuh<;1pvoi thl,tct€: nhii'ngnguainghic$nMorphin£huangphaitangli€u d~dapungnhudu gay earngiacsangkhoai. K€t qua£ht!cnghic$mdachothclyquatht!cco st!khacbic$tv~ho~tinh giamdatieuaMorphinkhithayd6ieachsii'd~ngK92.ChothclythemmQtkha nangungdl;lngnii'acuaSaponinNhansamtrangvai tra earnungenzym chuy~nhoala: co th~di~uehinhdu'<;1ctaed~ngcuathu6etheoymuon.N€u mu6ntangtacdl;lnggiamdau.d6ngthaigiamkhananggay nghic$ndolu<;1ng IOnMorphint6ndQngngoairebaa(99%)thi lien sa d~ngcling lucMorphin (li~unho-hdn)voiK92. Khi sli'dl;lngMorphindaingay,d~giambotdQc-tInh- dost!tichIllY theoehuky "ruQtgan"coth~chobc$nhnhanu6ngK92 lien~e. Nho khanangcamungenzym,ch€ ph5mK92 sedongvai traquantrQng trongchudngtrinhqu6cgiaphangch6ngmatuynhotaed~ngc~tedn,h6i ph~csuekhoe,vagiamkhanangtainghic$n[142]. Toml~i,khanangungdl,lIlgcuaSaponinNhansamt~ptrungchuyellvao 2 linh vt!csail: Thayd6iho~tIt!ceuathuoedungchungtheeymu6ncuanguoith~ythu6c b~ngeachxuctaccacphanungoxykhii'trongquatrinhchuy~nhoathu6c ho~ctangcuongv?nchuyenthu6cquamango 165 Giam ho<,1ttfnhva 10<,1icaccha'tdQcb~ngcachkichho<,1tmQts6 phanling cQngh<Jptrongcoth6. Tuy Saponintrongch6phfunK92 la cuaNhansam,nhungchungtoi dii xacdinhtmhquylu~tsinhhQccuaSaponintronghQAraliaceae,nennhung lingdl:mgtrensecoph<,1mvi lIngdvngrQngdi bon,d~cbi~tla co th6t~n dvngnhungdu<Jcli~uclinghQd~Id6m,d~tr6nghonNhansamd6t<,10ngu6n nguyenli~uvah<,1giathanhsanph.1m,nhu:Binh lang,Ngii giabl.... 4)sa d1:lngif thuyttearnzlngenzymdi phanrichvai fro cuaNhansamtrongbili thuoccdphl1angBd Trungich Kili: Khi nghienCUutIchh<JpDongTay y ta tha'yY hQcc6truyenchill anhhudng SaDsaccualy lu~ntri6thQcphudngBong. Cac hQcthuy6tamduong,ngiihanh, t<,1ngtu<Jng,kinh l<,1c,thuyboa...chiph6i roandi~n,tu nguyennhanb~nhsinh, phuongphapch.1ndoan,pheptilc tIt b~nhd6n cach ca'ut<,10nQi dungphuong thu6c,ch6bi6nthu6c,phan10<,1ithu6c. Phuongthu6cY hQcc6 truy€n it khi chi co 1 vi thu6c,ma thuangbaag6m nmeuvi thu6c,m6idu<Jcli~usedamnh~nmQthaynhieuvaitrakhacnhautrong tUngphuongthu6c.Chinhvi the.nenkhi sosanhvoi tandu<Jcthi1tudi6md~c tningnha'tcuaphuongthu6cyhyec6truyen13.tmhdad<,1ng,phlih<JpvoitUngca th6,tunggiaido<,1ndi~nti6ncuab~nh,d6ngthail<,1iit dQch<,1i. N6u xacdinhvai tracuacaevi thu6crheaQuan,Thftn,Ta, Sli theoquail di6mc6truyen(phftn1.5),tmkhaini~mtUonglac thu6ccuay hQcc6truyenco m6ilien quailnhu'th6naovoihi~ntu<Jngcamlingenzymchuy6nboacuasinh hQchi~nd<,1i? 166 Gi6ngnhu'y hQcc6truy~n.hi~uquacuatu'dngtacthu6chi~ndg.isegayra cactacdl;lngkhonghofmroanla t6ngcuaphepcQng:1cQngvdi 1khongphai bftng2,maco th61On.hdn2nitnhi~u,clingcokhi 19.ibftngO. Sl;i'camungenzymchuy6nhaathu6cse lamgiamthaigianbanphan.huycua thu6c,quadolamthayd6itacd1p1gvadQctinhcuathu6c.TrongmQtbaithu6c, caccha"tcamungenzymchuy~nboathu'angthlkhongth6la Quanmacoth61a Th~n,hayTa,haySu Qualy lu~ntu'dngmcthu6c uay'hQcB6ngphu'dng.thlh<lpcha'tSaponincua Nhansamtrangche'ph~mK92cos1;1'tu dngd6ngkichho~tenzymchuy6nboa,do ciamagayracaetacdQng: Giamthaigianbanphanhu~rAntipyrin,co khanangNhansamdamnhi~m vaitraSu Khi sadl;lngd6ngthaivdiParacetamol,Insulin,Morphindi!lamgiatangtac dl;lngd~ctricuacacdu'Qcphimnay,Nhansamcoth6dongvaitraTh~n. Khi sadl;lngtru'dc3ngay,Nhansamlamtangt6cdQchuy6nboaCadellva Morphin,dodolamgiammcdl;lngd~ctricuathu6cnguyenthuy,theoDongy tillday1avaitracuasa. TrenchUQtnhi6mdQcCC4,phongXg.:NhansamcotacdlJnggiaidQc,mall chongh6iphl;lCcacchisO'huye'thQc,sinhboa,sinhly cuasucv~thanghi~m, dayclingIamQtnhi~mVl;leuasa. Giamtll~ehuQtche'tdotu'dngtaccuaParacetamolvdi acidAcetic,mcdl;lng naychotha'y:Nhansamcoth~lamnhi~mVl;lcuasa. Ne'ud6ichie'uvdiphu'dngphapxacdinhvaitracuacacvi thu6ctheoyhQcc6 truy~nthlSaponincuaNhansammytungtru'anghQpCl;lth6,co nhi~mVl;lcua Th~n(h6trQ,tangtacdl:mgcuathu6cdungchung);ho~ccuaSu(d§:nthUDC,giai quye'tacdl:mgphl,l,boahoansl1manhli~teuadQceha't). 167 Vic%cxacdinhvaitracamlingenzymcuaNhansamtrongch€ phc1mK92,da: morQngph~mvi ungd\,mgcuaNhansamnoiriengvabaiBTIK noichung: Nhansamkh6ngnhungla1:h~n,maclingcoth~dongvaitracua511. Bai BTIK ngoaitacd\lngc6trUy€ncancoth~dunglamthu6cgiclidQc,di€u chinhtacd~ngcuacacduqcphc1md~ctrikhidungchungrheachi€u huangco lqi chovic%cdi€u tri [142].