The effect of anthraquinones in daiokanzoto on increasing the synthesis of sennoside A-metabolic enzyme derived from bifidobacteria
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(2) 216. Me c ha ni s m ofa c t i ono fRGonSAme t a bol i s m. e f f e c tofame di c i nea nd r e l i e vi ng s i dee f f e c t s ,by pha r ma c ol ogi corpha r ma c oki ne t i ca c t i on.Wepr e s e nt e d e vi de nc et ha tt heme t a bol i ca c t i vi t yofs e nnos i deA i n i nt e s t i na lba c t e r i awa ss i gni f i c a nt l ya c c e l e r a t e dwhe n bDgl uc opyr a nos i de ( RG)i nr hu ba r bo r r he i n 8Ol i qui r i t i n( LQ)i ngl yc yr r hi z ac oe xi s t e dwi t hs e nnos i de e nnos i deA wa s A.Mor e ove r ,t hep ur ga t i vea c t i ono fs s i gni f i c a nt l yi nt e ns i f i e dwhe nRG a ndLQ we r ec o7, 8) a dmi ni s t e r e dor a l l yt omi c e . The s er e s ul t ss how t ha t t he i nf l ue nc e oft he s ec ons t i t ue nt so nt he f a t e of r he i na nt hr onet r a ns f or me df r om s e nnos i deA ma ypr ovea c t i onofs e nnos i deA.Thr ought he s e mot et hepur ga t i s t udi e s ,weha ver e c ogni z e d au s e f uli nt e r a c t i on i n r ,we DKT,whi c hha smu l t i pl ec ons t i t ue nt s .Howe ve ha dn ote l uc i da t e dt heme c ha ni s m ofa c t i onbywhi c h t he s ec ons t i t ue nt sa c c e l e r a t es e nnos i deA me t a b ol i s m. oc l a r i f ys uc hame c ha ni s m. Thepr e s e nts t udyi nt e nde dt. HOH2C HO HO. O. O. O. OH. OH COOH O. Fi g.1 Che mi c a lSt r uc t ur eofRhe i n8ObDGl uc opyr a nos i de. Mat e r i al sandMe t hods Mat e r i al s :Se nnos i deAa ndpur omy c i nwe r epur c ha s e d f r om Wa koPu r eChe mi c a lI ndus t r i e s( Os a ka ,J a pa n) . Rhe i nwa spur c ha s e df r omFuna kos hiCo. ,Lt d.( Tokyo, bDgl uc opyr a nos i dewa si s ol a t e d J a pa n) .Rhe i n8Of r om r huba r b( LotNo.100901,Toc hi mot ot e nka i do, Os a ka ,J a pa n)a nd wa si de nt i f i e da c c or di ng t ot he 8) hodi napr e vi ouspa pe r . Li qui r i t i nwa si s ol a t e d me t f r om g l yc yr r hi z a( LotNo.050202,Toc hi mot ot e nka i do, db yc omOs a ka ,J a pa n) ,a ndi t ss t r uc t ur ewa si de nt i f i e nd13CNMRda t awi t ht hos er e por t e di n pa r i ngi t s1Ha 9) lot he rr e a ge nt swe r eofa na l yt i c a l t hel i t e r a t ur e . Al gr a de . LACB Gr a nul a rPowde rN a sbi f i doba c t e r i a( e a c h ma nd gr a mi nc l udi ng1 0mgofBi f i dobac t e r i um l ongu Bi f i dobac t e r i um i nf ant i s )wa spur c ha s e df r om Kowa. Co. ,Lt d.( Ai c hi ,J a pa n) .Thi ogl yc ol l a t eme di um wa s pr e pa r e d by s us pe ndi ng 5. 86 g o f Thi ogl yc ol l a t e Me di umFl ui d・ Ni s s ui ・pur c ha s e df r omNi s s uiPha r ma c e ut i c a lCo. ,Lt d.( Tokyo,J a pa n)i n100mLofwa t e r , s s ol vet heme di um c ompl e t e l y,a nda ut oboi l i ngt odi 2 ℃ e s s ur e( a t121 )f or20mi n. c l a vi nga t15l bs / i n pr Ul t r a pur edi s t i l l e dwa t e rwa spr e pa r e dwi t hde i oni z e ddi s t i l l e d wa t e r .Al lot he rc he mi c a l swe r ea na l yt i c a l r e a ge nt -orHPLCgr a dec omme r c i a lpr oduc t s . r i me nt swe r ea l lc a r Ani malpr e par at i on:Ani ma le xpe r i e douti na c c or da nc ewi t ht heGui de l i ne sf orAni ma l Expe r i me nt a t i onofFukuya maUni ve r s i t y.Ma l eddY g3040g,we r eobt a i ne df r omSHI MI ZU mi c e ,we i ghi n La bor a t or ySuppl i e s( Kyot o,J a pa n)a ndh ous e di na12 ora tl e a s tonewe e k hl i ght da r kc yc l ea t21t o24℃ f be f o r et hee xpe r i me nt s .The ywe r egi ve nf r e ea c c e s st o f ooda ndwa t e rbe f or et hee xpe r i me nt s . Chr oma t ogr aphi cc ondi t i ons :TheHPLC a ppa r a t us wa sa n Agi l e ntTe c hnol ogi e s 1100 Se r i e ss ys t e m ( Wa l dbr onn,Ge r ma ny)c ons i s t i ngo fabi na r ypump,a n r ,at he r mos t a t t e dc o l umnc ompa r t me nt ,a nd a ut os a mpl e aphot odi odea r r a y( PDA)de t e c t or .Al lmodul e sa nd ms t a t i on da t ac ol l e c t i onwe r ec ont r ol l e dbyAgi l e ntChe s of t wa r e .Thec ol umnwa saTSKge lODS8 0Ts QA r e ve r s e dpha s ec ol umn,pa r t i c l es i z eofpa c ki ng5mm, 6mm i . d.( Tos oh,Tokyo,J a pa n) .Themobi l e 150× 4. 1 c a . pha s ewa sag r a di e nts ys t e m wi t h 200 mL・ L ( 0. 017%)phos phor i ca c i di nwa t e r( A)a nda c e t oni t r i l e ( B) ,whi c hwe r ede a e r a t e dbys oni c a t i onbe f or eus e .The spe r f or me df r om19t o20% Bf or3 e l ut i onpr ogr a mwa mi n ,20t o2 1% Bf or5mi n,as t e pwi s ei nc r e a s et o43% Bf o r8mi n,a ndas t e pwi s ei nc r e a s et o90% Bf or5mi n qui l i br a t i o npe r i odof12mi nwa s f orwa s hi ng.A r e e us e dbe t we e ni ndi vi dua lr uns .Thef l ow r a t ewa s1. 0 1 .Thei nj e c t i onvol umewa s5mL.Thec ol umn mL・ mi n ℃ t e c t i onwa ve l e ngt hwa s t e mpe r a t ur ewa s5 0 .Thede s e ta t265nmf orde t e r mi na t i ona ndi nt her a ngeof200 t o500nm f orva l i da t i onofpe a kpur i t y. i cac t i vi t yofs e nnos i deA by As s ayi ngt heme t abol mo us ei nt e s t i nalbac t e r i a:Fr e s hf e c e so bt a i n e df r om mi c ewe r ehomoge ni z e di n320vol ume sof0. 01M a t eb uf f e r( pH 7. 4)bybubbl i ngwi t h pot a s s i um p hos ph st oe l i mi na t ea i r ,a nd t he s e di me nt swe r e CO2 ga.
(3) J .Tr a d.Me d.( Vol . 30No. 5/ 62 013). r e move dbyf i l t r a t i ont hr oughga uz e .Se nnos i deA( 0. 4 mM)wa spr e p a r e dwi t h0. 01M p ot a s s i um phos pha t e bu f f e r .RG,r he i n,a ndl i qui r i t i n,e a c ha tac onc e nt r a t i on of2mM,we r epr e pa r e dwi t h0 . 5% s odi um hydr oge n c a r bona t e .Thea s s a ys a mpl e sp r e pa r e df r om mi xi ng os i deAa nde a c hc ons t i t ue nts a me qua la mount sofs e nn pl e .Tu be sc ont a i ni ngt hea s s a ys a mpl e s( 0. 25mL)a nd or t hef e c a ls us pe ns i on( 1mL)we r ei nc uba t e da t37℃ f di f f e r e nti nc uba t i onpe r i ods( 2,4,8,24h)unde ra na e r obi cc ondi t i ons .Ana e r obi cpr oc e dur e swe r ec a r r i e dout r obi cj a rwi t ha nAna e r oPa c k( Mi t s ubi s hi us i nga na na e Ga sChe mi c a l ,Tokyo,J a pa n) .Ther e a c t i onwa si mme i ca c i d di a t e l ys t oppe dbya ddi ng0. 425% v/ vp hos phor i nme t ha nol( 1. 25mL) .Af t e rc e nt r i f uga t i ona t1500g f or5mi n,t hes upe r na t a ntwa spa s s e dt hr oughMi ni s a r t ,Tokyo,J a pa n)a nds ubj e c t e dt o RC15( J a pa nSa r t or i us HPLC.Thec ont r olpr oc e s si nvol ve da ni nc uba t i onmi xt ur ea t0mi n,a sme nt i one da bove .Me t a bol i cr a t ewa s c a l c ul a t e dbyt hepe r c e nt a geoft hec ont e ntofs e nnos i de Ai nt hei nc uba t i onmi xt ur ec omp a r e dwi t ht ha ti nt he c ont r ol . i t ue nt s on t he s ynt he s i s of Ef f e c to fDKT c ons t s e nnos i deAme t abol i ce nz ymebymo us ei nt e s t i nal f l or a:Fr e s hf e c e sobt a i ne df r om mi c ewe r ehomoge 01M pot a s s i um phos pha t e ni z e di n20vol u me sof0. s .RG,r he i n, buf f e r( pH 7 . 4)bybubbl i ngwi t hCO2 ga a ndl i qui r i t i n,e a c ha tac onc e nt r a t i o nof0. 4mM,we r e pr e pa r e dwi t h0. 01M p ot a s s i um phos pha t ebuf f e r .The spr e pa r e df r om mi xi nge qua la mount s s a mp l emi xt ur e ofe a c hc ons t i t ue nts a mp l ea ndt hef e c a ls us pe ns i on. Pu r omyc i nwa sa dde dt ot hes a mp l emi xt ur e sa tf i na l t r a t i onso f1mgt o1mg/ mL.Thes a mp l emi xc onc e n or24hunde ra na e r obi c t ur e swe r ei nc uba t e da t37℃ f c ondi t i ons .RG,r he i n,a ndLQwe r er e mo ve df r om t he p r e i nc uba t e ds a mpl e sus i nga na ni one xc ha nger e s i n, Tos oh,Tokyo,J a pa n) ,a ndwe r e TOYOPAKDEAEM ( c onf i r me dt oha venope a kbyHPLC.Se nnos i deA( 0. 2 mM)wa spr e pa r e dwi t h0. 01M p ot a s s i um phos pha t e nn os i deA ( 0. 25mL)wa sa dde dt ot hep r e buf f e r .Se i n c uba t e ds a mpl ewi t he l i mi na t e dc ons t i t ue nt s( 1mL) , or24h a ndt h ea dde ds a mpl e swe r ei nc uba t e da t37℃ f unde ra na e r obi cc ondi t i ons .Ther e a c t i onwa si mme di a t e l ys t oppe dbya ddi ng0 . 425% v/ vphos phor i ca c i di n e nt r i f uga t i ona t1500gf or me t ha nol( 1. 25mL) .Af t e rc 5mi n,t hes upe r na t a ntwa spa s s e dt hr oughMi n i s a r tRC. 217. 15a nds ubj e c t e dt oHPLC. Ef f e c tofr he i n8 ODgl uc opyr anos i deont hes ynt he s i sofs e nnos i deAme t abol i ce nz ymebybi f i dobac s t e r i a:RG( 0. 4mM)wa spr e pa r e dwi t hwa t e r ,a ndwa s . mi xe dwi t haTGCme di um bybubbl i ngwi t hCO2 ga LACBGr a nul a rPowde rN ( 2mg )wa spr e pa r e dwi t h t hes a mpl emi xt ur e( 1mL) .Pur omyc i nwa sa dde dt ot he t i onsof0. 1t o10mg/ s a mpl emi xt ur e sa tf i na lc onc e nt r a or24 mL.Thes a mpl emi xt ur e swe r ec ul t ur e da t37℃ f hunde ra na e r obi cc ondi t i ons .Se nnos i deA ( 0. 2mM) wa spr e pa r e dwi t h0 . 01M pot a s s i um phos pha t ebuf f e r . ydr oge nc a r bonRGwa spr e pa r e dwi t h0. 5% s odi um h a t e .Thea s s a ys a mpl e swe r emi xe dwi t hs e nn os i deA. Tube sc ont a i ni ngt hea s s a ys a mpl e s( 0. 25mL)a ndt he ei nc uba t e da t37℃ f or24 c ul t ur e ds a mpl e s( 1mL)we r hunde ra na e r obi cc ondi t i ons .Ther e a c t i onwa si mme di a t e l ys t oppe dbya ddi ng0. 425% v/ vphos phor i ca c i di n me t ha nol( 1. 25mL) .Af t e rc e nt r i f uga t i ona t1500gf or 5mi n,t hes upe r na t a ntwa spa s s e dt hr ou ghMi ni s a r tRC 15a nds ubj e c t e dt oHPLC. aa r es ho wna st heme a n± St at i s t i c ala nal ys i s :Da t S. D.St a t i s t i c a lc ompa r i s onsbe t we e nt wogr oupswe r e ma deus i ngunpa i r e dtt e s t( KyPl ot ,Kye nc eI nc . ) .To nne t t ' st e s t( KyPl ot , c ompa r emor et ha nt wog r oups ,Du Kye nc eI nc . )wa sus e d.Apr oba bi l i t yv a l ueofp<0 . 05 wa sc ons i de r e dt oi ndi c a t es t a t i s t i c a ls i gni f i c a nc e .. Re s ul t sandDi s c us s i on Theme t abol i cac t i vi t yo fs e nnos i deAbyc ons t i t ue nt s ac c e l e r at i ngs e nnos i deAme t abol i s m:DKTi sma i nl y tc ons i s t soft wo us e da sal a xa t i veKa mpome di c i ne ;i c r udedr ugs ,r huba r ba ndgl yc yr r hi z a .Se nnos i deA,t he ma i npur ga t i vec ons t i t ue ntofr huba r b,e xhi bi t spur ga i vea c t i vi t ybybe i ngme t a bol i z e dbyi nt e s t i na lba c t e r i a . t Thusf a r ,weh a vec l a r i f i e dt ha tRGa ndLQc ont r i but e e nnos i deA bya c c e l e r a t i ng t ot hepur ga t i vea c t i onofs 7, 8) Howe ve r ,weha dnotc l a r i f i e d i t sme t a bol i ca c t i vi t y. t heme c ha ni s mo fa c t i onbywhi c ht he s ec ons t i t ue nt sa c nt s c e l e r a t es e nnos i deA me t a bol i s m.The s ec ons t i t ue s i gni f i c a nt l ya c c e l e r a t e dt he me t a bol i ca c t i vi t y of s e nnos i deAb ymo us ei nt e s t i na lba c t e r i a .Ass howni n es e nnos i deAme t a bol i s ml i ke Fi g.2,LQa c c e l e r a t e dt h.
(4) 218. Me c ha ni s m ofa c t i ono fRGonSAme t a bol i s m. Metabolic rate of SA (%). 100. *** ***. 80. ***. howas i gni f i c a ntdi f f e r e nc e .Thus ,i twa s LQd i dnots s ugge s t e dt ha ta nt hr a qui none s ,owi ngt ot he i rs ke l e t on, a c c e l e r a t e ds e nnos i deA me t a bol i s m byi nduc i ngt he me t a bol i cba c t e r i aort he i re nz ymer e l a t e dt os e nnos i de Ame t a bol i s m.. 100 Metabolic rate of SA (%). ahype r bol i cc ur v ec omp a r e dwi t ht ha tofs e nnos i deA a l o nea sac ont r ol ,r a i s i ngt hepos s i bi l i t yt ha tLQ ma y i nvol vequa l i t a t i v ec ha nge so fs e nnos i deAme t a bol i c e nz yme .Ont heo t he rha nd,RGd i f f e r e di nt e r msoft he me t a b ol i cc ur veofs e nnos i deAc omp a r e dwi t ht ha tof l yc onofRG,e xhi bi t e dt hes a mea c t i LQ.Rhe i n,a na g va t i ona sRG.The s ef i ndi ngss ugge s t e dt ha tt heme c ha a t e ni s m ofa c t i on by whi c ha nt hr a qui none sa c c e l e r s e nnos i deA me t a bol i s m ha sad i f f e r e ntpa t t e r nf r om t ha tofLQ.. ***. 80. ***. 60 40 20. 60 0 ***. 40 20 ** **. 0 2 4. Rhein. RG. LQ. bDg l uc opyr a Fi g.3 Ef f e c tofPr e i nc uba t i onwi t hRhe i n8Onos i de( RG) ,Rhe i n,a ndLi qui r i t i n( LQ)onMe t a bol i s mo f Se nnos i deA( SA) Ea c hc ol umnr e pr e s e nt st heme a n± S. D.of3s a mpl e s .***p <0. 001,s i gni f i c a ntdi f f e r e nc ef r om c ont r ol( Dunne t t ・ st e s t ) .. ***. 0. Control. 8. 24. Incubation time (hr) SA 㩿0.2 mM㪀㩷. SA + RG 㩿1 mM㪀㩷. SA + Rhein 㩿1 mM㪀㩷. SA + LQ 㩿1 mM㪀㩷. bDgl uc opyr a nos i de( RG) ,Rhe i n, Fi g.2 Ef f e c t sofRh e i n8Oa ndLi qui r i t i n( LQ)onMe t a bol i s m ofSe nnos i deA( SA) Ea c hpoi ntr e pr e s e nt st heme a n± S. D.of3s a mpl e s .**p<0. 01, * **p<0. 001,s i gni f i c a ntdi f f e r e nc ef r om SA( Dunne t t ・ st e s t ) .. I no r de rt oc l a r i f yt heme c ha ni s mofa c t i onbywhi c h t heme t a bol i ca c t i vi t yofs e nnos i deAi sa c c e l e r a t e d,t he e f f e c tont hes ynt he s i sofs e nnos i deAme t a bol i ce nga t e d us i ng pu r omyc i n. z yme mol e c ul e swa si nve s t i Pur omyc i ni nhi bi t spr ot e i ns ynt he s i st os uppr e s st he e l onga t i onofpe pt i dea tar i bos ome ;i ti nhi bi t snotonl y hes e nnos i deAme t a bol i ce nz ymebuta l lpr ot e i ns ynt. Metabolic rate of SA (%). 100. I nf l ue nc eo fc ons t i t ue nt st hatac c e l e r at es e nnos i deA me t abol i s m ont hes ynt he s i sofs e nnos i deAme t abol i c e nz ymebyi nt e s t i nalbac t e r i a:Toe xa mi net hei nf l ue nc eofc ons t i t ue nt sa c c e l e r a t i ngs e nnos i deA me t a bocba c t e r i aort he i re nz yme , l i s mons e nnos i deAme t a bol i t hes ol ut i onsoft he s ec ons t i t ue nt swe r ea dde dt of e c a l s . s us pe ns i ons ,a ndt hemi xt ur e swe r ei nc uba t e df or24hr Af t e re xc l udi nge a c hc ons t i t ue ntf r omt hemi xt ur eus i ng a na ni on e xc ha nger e s i n,t hepr e i nc uba t e ds a mpl e s t hs e nnos i deA( Fi g.3) .Thepr e we r es uppl e me nt e dwi i nc uba t e df e c a ls us pe ns i on,mi xe dwi t hRG,s i gni f i i deA c a nt l ya c c e l e r a t e dt heme t a bol i ca c t i vi t yo fs e nnos c omp a r e dwi t ht hec ont r ol .Aswe l la sRG,r he i ns i gni f i c a nt l ya c c e l e r a t e dt heme t a bol i ca c t i vi t yofs e nnos i deA.. 80. Control Pre-incubation with RG *** ***. 60 40 20 0. 0. 1. 10. 100. 1000. Puromycin (µg/mL). Fi g.4 Ef f e c tofPr e i nc uba t i onwi t hRhe i n8ObDg l uc opyr a nos i de( RG)a ga i ns tSe nnos i deAMe t a bol i cEnz ymeTr e a t e d wi t hPur omyc i n Ea c hc ol umnr e pr e s e nt st heme a n± S. D.of3s a mp l e s .***p <0. 001,s i gni f i c a ntvs .c ont r olbyunpa i r e dtt e s t ..
(5) J .Tr a d.Me d.( Vol . 30No. 5/ 62 013) 10, 11) t he s i sofba c t e r i a . Asar e s ul t ,i nc r e a s i ngRGc or r e s ponde dt od e c r e a s e ds e nnos i deA me t a bol i s m oft he pr e i nc uba t e ds a mpl ewi t houtRG bypur omyc i ni na nd e ntma nne r( Fi g.4) .Cons e que nt l y,i twa s dos e de pe c l a r i f i e dt ha tRG i nduc e dt hes ynt he s i so fame t a bol i c e nz ymeofi nt e s t i na lba c t e r i ar e l a t e dt os e nnos i deAme t a bol i s m.. I nf l ue nc eo fc o ns t i t ue nt st hatac c e l e r at es e nnos i deA me t abol i s m ont hes ynt he s i sofs e nnos i deAme t abol i c e nz ymebybi f i dobac t e r i a:Se nnos i deAi sa ni na c t i ve gl yc os i de ,a ndi st r a ns f or me dt oa na c t i veme t a bol i t e , i da s ede r i ve df r om bi f i doba r he i na nt hr one ,bybgl uc os ***. Metabolic rate of SA (%). 100 80 60 40 20 0. Control. RG. Fi g.5 Ef f e c tofCul t ur ei nBi f i doba c t e r i awi t hRhe i n8ObDgl uc opyr a nos i de( RG)onMe t a bol i s m ofSe nnos i deA( SA) Ea c hc ol umnr e pr e s e nt st heme a n± S. D.of3s a mp l e s .***p <0. 001,s i gni f i c a ntvs .c ont r olbyunpa i r e dtt e s t .. Metabolic rate of SA (%). 100. ***. Control Culture with RG. ***. 80 60. ***. 40 20 0. 0. 0.1. 1. 10. Puromycin (µg/mL). Fi g.6 Ef f e c tofCul t ur ei nBi f i doba c t e r i awi t hRhe i n8ObDgl uc opyr a nos i de( RG)a ga i ns tSe nnos i deAMe t a bol i cEnz yme Tr e a t e dwi t hPur omyc i n Ea c hc ol umnr e pr e s e nt st heme a n± S. D.of3s a mp l e s .***p <0. 001,s i gni f i c a ntvs .c ont r olbyunpa i r e dtt e s t .. 219. 25) The r e f or e ,wee xa mi ne dt hei nf l ue nc eofRG c t e r i a . ons e nnos i deAme t a bol i ce nz ymede r i ve df r om bi f i doba c t e r i a( Fi g.5) .Thec ul t ur e dbi f i doba c t e r i a ,mi xe d wi t hRG,s i gni f i c a nt l ya c c e l e r a t e dt heme t a bol i ca c t i vi t y ofs e nnos i deAc ompa r e dwi t ht hec ont r ol . ef e c e s ,i nc r e a s i ngRG Si mi l a r l yt ot hec a s ei nmous wa sde c r e a s e dbypur omyc i ni nados e de pe nde ntma nne r( Fi g.6) .Tha ti st os a y,t heme c ha ni s m ofa c t i ono f r i f i e d:i ti nc r e a s e dt hes ynt he s i sofs e nnos i de RGwa sc l a Ame t a bol i ce nz ymed e r i ve df r om bi f i doba c t e r i a ,t he t e r i a . ma i ns e nnos i deAme t a bol i cba c Ka mpome di c i ne sa r eor a l l ya dmi ni s t e r e d,a ndt he y c ont a i nma nyki ndsofgl yc os i de sa st hema i na nd/ ora c s egl yc os i de sa r enota bs o r be da nd t i vec ons t i t ue nt s .The e nt e rt hel owe rpa r toft hei nt e s t i ne .Mos tgl yc os i de s uc i ngbma ybeme t a bol i z e dbyi nt e s t i na lba c t e r i apr od gl uc os i da s e sbe f or ebe i nga bs or be di nt ot hebody.Tha t i s ,t hei nt e s t i na lba c t e r i ar e l a t e dt ot heme t a b ol i s m of or a l l ya dmi ni s t e r e dgl yc os i de sa r ei mpor t a ntt ounde r 1214) I no r de rt oi nve s t i s t a ndpha r ma c ol ogi c a le f f e c t s . ga t es uc hme c ha ni s ms ,wee xa mi ne dt hea c t i va t or sof gl yc os i det r a ns f or ma t i onus i ngours c r e e ni ngme t hod. ouss t udyt ha tt heme t a bol i ca c t i vi t y Wef oundi napr e vi ofs e nnos i deA i ni nt e s t i na lba c t e r i awa ss i gni f i c a nt l y nnos i de a c c e l e r a t e dwhe nRG o rLQ c oe xi s t e dwi t hs e 6, 8) I na ddi t i on,t hepur ga t i vea c t i onofs e nnos i deA A. wa ss i gni f i c a nt l yi nc r e a s e dwhe nRG orLQ wa sc o7, 8) I nt hi ss t udy,wema i nl y a dmi ni s t e r e do r a l l yt omi c e . e xa mi ne dt hei nf l ue nc eofRG o nt hes ynt he s i sof s e nnos i deAme t a bol i ce nz yme .Asar e s ul t ,i twa sc l a r i c c e l e r a t e dt he me t a bol i ca c t i vi t y of f i e dt ha tRG a s e nnos i deAbyi nt e s t i na lba c t e r i a ,e s pe c i a l l ybyi nc r e a s i ngt hes ynt he s i sofs e nnos i deAme t a bol i ce n z ymede r i ve df r om bi f i doba c t e r i a ,t he ma i ns e nnos i de Ame t a bol i cba c t e r i a .Ka mpo me di c i nei nvol ve sc r ude ons t i t ue nt s ,a ndt hei nt e r a c t i on dr ugsba s e donmul t i p l ec be t we e ne a c hc ons t i t ue nti si mpor t a ntf ort he i ra c t i vi t y, di c i nea ndr e s uc ha sbyr e i nf or c i ngt hee f f e c tofame l i e vi ngs i dee f f e c t s .I nt hi ss t udy,weha ver e ve a l e dt he pur ga t i ve pr omot i nga c t i onofs e nnos i deA i nDKTby et oa nt hr a qui none sa ndf l a vonoi ds .We adi f f e r e ntmod s ugge s tt heu s e f ul ne s sofKa mpome di c i nea sdr ugs ba s e d on mu l t i pl ec ons t i t ue nt s ,r a t he rt ha n We s t e r n ugswi t has i ngl ec ons t i t ue nt . dr.
(6) 220. Me c ha ni s m ofa c t i ono fRGonSAme t a bol i s m. Ac knowl e dge me nt s. Ts ur ut a ,Y. ,Oka mu r a ,N. :Hi ghpe r f or ma n c el i qui d l i cs t udyof c hr oma t ogr a phi cde t e r mi na t i ona ndme t a bo. Thea ut hor sa r egr a t e f ult oMr .Aki r aTa ka oka ,Mr . Mi t s uhi r oMi z ut a ni ,a ndMs .Yuki koYa ma mo t of or t he i rt e c hni c a la s s i s t a nc e .. s e nnos i deAi nd a i oka nz ot obymous ei nt e s t i na lba c t e r i a . Che m.Phar m.Bul l . ,59,11061109,2011. 7) Ma t s ui ,E. ,Ta ka ya ma ,K. ,Sa t o,E. ,Oka mur a ,N. :The i nf l ue nc eo fgl yc yr r hi z aa nda nt i bi ot i c sont hepur ga t i ve a c t i onofs e nnos i deA f r om da i oka nz ot oi nmi c e .Bi ol .. Re f e r e nc e s. Phar m.Bul l . ,34,1438144 2,2011. 8) Ta ka ya ma ,K. ,Ts ut s umi ,H. ,I s hi z u,T. ,Oka mur a ,N. :. 1) Mi yos hi ,A. ,Ma s a mune ,O. ,Fukut omi ,H. ,Mor i ,H. ,. Thei nf l ue nc eofr he i n8ObDgl uc opyr a nos i deo nt he. Mi wa ,T. ,Koj i ma ,K. ,Aono ,M. ,Na ka j i ma ,M. :The. pur ga t i vea c t i ono fs e nnos i deA f r om r huba r bi nmi c e .. c l i ni c a le f f e c tofTSUMURA da i oka nz ot oe xt r a c tgr a n-. Bi ol .Phar m.Bul l . ,35,22042208,2012.. ul e sf ore t hi c a lus e( TJ 84)bydoubl ebl i ndt e s ta ga i ns t t hec ons t i pa t i on.Gas t r oe nt e r ol ogy ,18,299312,1994. 2) Ma t s umot o,M. ,I s hi ge ,A. ,Yuz a wa ,Y. ,Kondo,M. ,. 9) Ya ha r a ,S. ,Ni s hi oka ,I . :Fl a vonoi dgl uc os i de sf r oml i c or i c e .Phy t oc he m. ,23,21082109,1984. 10) Ya r mol i ns ky,M. B. ,Del aHa ba ,G. L. :I nhi bi t i onby. Mur a ma t s u,K. ,Wa t a na be ,K. :Pr omo t i onofi nt e s t i na l. pur omyc i n ofa mi no a c i di nc or por a t i on i nt o pr ot e i n,. pe r i s t a l s i sbybi f i doba c t e r i um s pp.c a pa bl eofhydr ol yz -. Pr oc .Nat l .Ac ad.Sc i .USA. ,45,17211729,1 9 59.. i ngs e nnos i de si nmi c e .PLoSONE,7,e 31700,2012. 3) Koba s hi ,K. ,Ni s hi mur a ,T. ,Kus a ka ,M. ,Ha t t or i ,M. , Na mba ,T. :Me t a bol i s m ofs e nnos i de sbyhuma ni nt e s t i na lba c t e r i a .Pl ant aMe d. ,40,225236,1980. 4) Ha t t or i ,M. ,Na mba ,T. ,Aka o,T. ,Koba s hi ,K. : Me t a bol i s m ofs e nnos i de sbyhuma ni nt e s t i na lba c t e r i a . Phar mac ol og y ,36,172179,1988.. 11) Na t ha ns ,D. :Pur omy c i ni nhi bi t i onofpr ot e i ns ynt he s i s : i nc or por a t i onofpur omyc i ni nt ope pt i dec ha i ns ,Pr oc . Nat l .Ac ad.Sc i .USA. ,51,585592,1964. 12) Koba s hi ,K. ,Aka o,T. :Re l a t i ono fi nt e s t i na lba c t e r i at o pha r ma c ol ogi c a le f f e c t sofgl yc os i de s .Bi os c i .Mi c r of l or a. , 16,17,1997. 13) Ki m,D. H. ,J ung,E. A. ,Sohng,I . S. ,Ha n,J . A. ,Ki m,. 5) I s hi ha r a ,M. ,Homma ,M. ,Kuno,E. ,Wa t a na be ,M. ,. T.H. ,Ha n,M.J . :I nt e s t i na lba c t e r i a lme t a bol i s m of. Kohd a ,Y. :Combi na t i onus eofKa mp ome di c i ne sa nd. f l a vono i dsa ndi t sr e l a t i ont os omeb i ol ogi c a la c t i vi t i e s .. dr ugsa f f e c t i ngi nt e s t i na lba c t e r i a lf l or a .YAKUGAKU ZASSHI ,122,695701,2002. 6) Ta ka ya ma ,K. ,Ma t s ui ,E. ,Koba y a s hi ,T. ,I noue ,H. ,. Ar c h.Phar m.Re s . ,21,1723,1998. 14) Ki m,D. H. :He r ba lme di c i ne sa r ea c t i va t e dbyi nt e s t i na l mi c r of l or a .Nat .Pr od.Sc i . ,8,3543,2002..
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