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    11 views8 pages

    Stevens Xanthohumol Human PK Paper 2014

    Uploaded by

    Michael Raharja Gani
    artikel

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 8
    0 ote enone Resear Anneve Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops ‘LeeCote Legette'2, Chanida Kemnpracha’, Ralph L. Reed", Jaewoo Cho, Gerd Bobo’, J Mark Christensen?, Rosita Rodriquez Proteau. Jonathan Q, Purnell and Jan & Stevens)? ‘Linus Paling nse, Oregon Site Univer, Cova, OR, USA *Cotago of Pharmacy, rego Sate Unvoray, Covell OR, USA 3Doparment of Anima ances and Rangel ‘Deparment ot Madele, Oregon Heath Sane Unive, Poland, OR USA Scop Xai (x bce rena Fo hp Aine pari okie PH xy war cance In en = 29) ad wean (2 = 29 dene {neonentton comp Dee ede Sj cco x pol dan f 20680 80 XN, Had encod 16,425,051. 3 48 12 2 ah 72, 9a 120 Pos of AN {dis meats, sentinel 09 rennin PN), ad ee {G2 wee meaty LEMS). Kenton (A) and eos were ‘eltng tvs among alte Level of PM md PN er dese mm ‘bjt The XN PX re showed pst coeeaton send Than ween 45 hater Ingestion. The msi XW concentrate Cpa wee 337g 8-2 gh a 120 2 magi forthe 20,6, aed 10 mp de, Paget Un nomrngrnca ‘nedeing he aes eth cre AUC an) 0 were 92:46 pg 3284 160 2 ny 863-38 pl fe the 30, an 18 pds eget. Te Me Tate oN as 20 he dN ore TD ng de, ‘ons: Xt arin paseo ten wth XN and 1X ojos Belg ome ccusng eee Keyword: Flavonoids / Hops Human metabolism Purmacoints Xathohurol Alain! upon intron ay befor fi ace ‘epblibersvebate Scans, Organ State Univers, Cora ‘on, usa seca in 283 1) Introduction ‘ype 2 des emerged mje pi els se ‘wean of spent on heh are cass, an {ein dewopent of te ree disease sho in enzo ota tna gee arian duatatd ey 20th Unie Stee {U5 Cones r Duan Cnt Ce) ete at 96 Amerans 5 iin seed Go Sates with 3% dagen ds 220 yeas of ae eng pe {adore kha ren vim abs raed oe tet neh cre cee f S17 tilon In 2012) Tp coe whieh cone tbeledingcassoda inie US cs ment fedige migget Aaeeide ight all in reeton andor mito of type 2 abe.) Pca cent eviece sige hat anal (0, peony ne ‘heat ara fr etic dace inn pe 2 ae 6 iveigaons ae shown at XN passes bral ange lagi sc wch a tant Ph ataasry 9} sn [0 nod rm ‘woman mame voll cl molto ain 1), Se ofthe bh hee and oti err eect of 8 yb ee oh te fe ctv of on ft mtb, 8 premarin {GP sich porns ger este aly an he Syne gest 1219. Te mor payee 5a mon fve tre eed (9) 3 et {sparen coven oad (2) at ‘netmlesar Wiel don undeges ena ‘dation BPN vis hepatic CYPIA 1 ga ‘iil ens 179. XW an 0 neg et eile emerson fe deneysutoutol hihi "ier crs no ete preying PN} 3PX 4 "ny impac ipsa gcse malin by cing end forte reat cep ches esd Fumes wel gees oe pl rea, ipl wasp aed hc avons 6 Nz be re pel hat ata andr rer rece sndte ‘leneiton i ak ed loner pla ipl ol he (urs Sar anced noe a me 3 owe psa aoe clare dp ‘eos! pd me On ee ae Zaha "a Dspe mens we Ini seen nia Seis, rei ed a 2 tele Pt, termine iparmacbinieP}prcs r XN elt estat eon nn goed sebale ydeome 2. Materials and methods 21, Human subjects Sy sales wee ered fre PK stay by eH ‘lnel Tanti! Reach Cen at Og Heth usin De a OU Rasen om, Snes Univesly (ONSU) tse on flowing ey ia ty mats inde (BM betwen 1-32 ee ‘raga seat i condos See oe ho texte set orn comme pr pt ‘Sit and magn fh a Sb! chance se deed ln Table LA proses and proeas Shing human bets were appro y cn I cere ith ilies of the OHSU an Oregon Sse Unity nse Ree Bord (IR Pres? 90057), Wien flor ens ine er dy atany te Hes sje tn and 3 women ‘wereld and comp he Pst Te were ‘resented sete vets ep In the sy The ay was gird wth he Clear laner 122 Woatmant rus Sbjct wee rnd bed ot gender oe of the faonng rl eset 26 e190 mq XN. sd wat ‘led 0,025 05,12 4 8 ae ough oe ‘tan interno ther Bled sap 244672. 56, $d 20 hmv clad sen pea Sub we Tle. Supt orn rhe kt Sie Foren) iene von dot bleh 2, 4872.96 a MO ad ‘has: bjt ese ting 2 afer Ob tine pit emit flowing tie, 8,729 a 0b rte Std cps nd ivetignrseelde ‘andre of sy weet sent 2 capi ere opr ing nl grade 6 pre XN Ponder (oar, RY. USA). Caps cntanel sl. hulaigsoopi mse a Noe Toren ed opine yeaa rv debe} Cope ere Felted oy Ce Phong (eta, OF ade ‘onniirnnpeann css tet al ‘ninco hte et eee begrang est, {plot tho 0 cape ae ome td never ‘tena and pe stay tester, 9 onthe ‘ftrge Al apse were fund we itn 10% of oe ‘itl oe, Cpe er anand dg i ‘eater lewd yin th mal lw {110 mL igus were conse ign 20 ‘na Lina C18 etn Phen Tareas, USA) lel wi gdint e016 ACN in 15.TFA nS 24 Sample preperation atoning ech oa draw, sampler wee sted ‘ere cum Ded conse a cxed wath an Irpain QD Vain A Dips Frain kes NL'USA) Somes were emigre hl ond ‘int won sore t-sample pce Ei Primi nek op 3 ut pa amps ‘ir condided to vey congo ensue by Represent plans mls fol este po ‘erate or puoi sales aie ‘nd ster las paren weeded is S/S ang sed acon monitoring SR) of pl samples bef enya ass: loving enjatic Iara nese in XN Sov wa nen and 3 ‘hears old no ng be dee (ot se salto were atc er ear er “retical af ate pam spe To oir ‘mesons war pts Shee fn 2 ono Ite snd ws pero anda eed proce from 2,2 and dsr oppor tr, XN rmoosaive was charac by LE-QTOP MS anc {SuppeingIrmstin Tie 1 3 2 ad detected when Speen sk ps samp el weed Jewingenpati hein ie fr ae ‘cumaichyrpncomid ofthe llocngcoonee ‘pn gut 004 Msn a baer 123 iso ath an tera sts 42S 22012 EHH Wg OH Cn aA Wn (01,10, mete eye sand led in otha Nora aro Pond BPH Oj ad Fate pomata suites (20 Upeaion “02 gt 10x erst vem" 0 Spee wer ined fr 2h at °C 2m cremcap es Faloingeeamtchydaysis ses erevoresed (09) ‘dct (13 00 pen, in or sagen ‘hew method was doped ing 8 4 mm paces of ‘Wea Mike per All sna ere aed a hupe mip wacion mcd ind of he pein teol a dercen wt 3) Te per sp ‘incon meds sera teeter ued hd ‘extacionInulig Ls sent se oer ler cn, {hd netgaor eee to eae men Meth ‘alton ser ih showed fate per stp “ction wend wt US aod sd Dra Adit Bilis n ems fury fs 18K eget $n e156 RSD) and reece fe 18% RSD] serene ‘lige comet ong A fl destin af ype ‘ripeacton mtd wb dale cheer In Pott pper sp ws ced each spe ae wih Seimned ine natn mt, Samples we died atthe per spe seit fea dessa oer Deri) Dred persia were atl th led (016 fac acto Smt by cing) and {aking Aer enon epperps enact ee ‘eid 1340 rn 2m aay LEMS {ing He SR ederim ee nd conse) XN and tale AP ad om, 25 Mase spoctomet LeMS/Ms canons fer quiifion of XN and its ‘mealies re ia hn dele nor peas ‘wor 2) Inbee LCA MS a ered ona ped yen 09 QTRAP ibid na Fei udp {tee ABS Cane Cad) peed st sae: temper f SOC with 2 nee vay of S00 {Gonstppie eprom of RN and mcr ‘ete schied an 02 50min Zeran M088 CR caren (gen Sots Cnr, CA, USA) ted wh pet of 206 salon (019 frm i a ACK eet oe O15 emi cd in 4 in fo ae af er denn of nie esp {ating SHO anion wee wel: me S979 fr ed 30 For don af ite ous, th lawn SRO tapon wan sue mf 8-019 for XN eon. sults A gandaplTOF mse pom (ABST “ple TOF 0, AB Se, Fae hy CA USA) wan ed te Cactsae XN conus Te 50 TiheTOF ‘gente n patie iow mde thx re peti of {Gor an pei S502. onogiacireise {Caln0, Janda yHDy ase 38 Imonolie (GFy095) hd ne (tO) vmitoans eo sere arate f inet in the TOF MS amis howe, {iy ane HN won wih 3 ae pe a S31873 pas fale for py S311) ws Siete in ptm se The homoge a Aor ole tne thw XM a cog soo a. 2 PK medel and parameters Mean asm concent ine pols fr both XN and [were ered ing Graph rs fre en ‘40h Son legs CA USA) Mannan pen concen (Go) tl i th Cn Ta ee teri {nt he ns encnrna Ste caves PX peters eres yng oncmprinetl med he ‘Speimetal XN psa oe vets tae dal ‘Optimize PX psc etiam te mal were ‘Sind ingress nd Winter {Winkel Sa Phang, Sams CA, USA) PE [ieee eins were ed tee fovng ‘ah: ser tnder te puna coment ine came {yn} le fe) tnd eel ely ces ‘Toe fie of one aba (fw 9 teed reniean menos dw ar aiid be 27. Senter ‘ang Sut Ana Sofware aS). Vion 98 GAS Ine, Cay NC, USA) te et dose and ener Pe prc of and te tele PROC GLE ih de 6 nd 180 X09, eer fa ad fae, {here Bd fie. To even {he Pn pratense tantra oth matrd eps aus Sal lean we dered st P00 ands tendency 00 «7030 441. PK paramoters of XM and its metas sing Hof fee XN were fant be very ow “Cron between lg fat nd fee pao Sted XN ee bt ot ea or 8 Teese mero pants fri ebaraton-) pee ‘he XM may ot acres tase eae 2 Sram ace mete he lng Fy beet ‘tae scat) XN conus ses ey ‘Serta efits nd a te ey rede pl ee Or eater king a el ‘o2ma Mecha ceca Kak an ‘Wa cnn of 2 en ‘cate Yeconeon Je flac capone of hy wp fo XN dei ine cps bter hr plana eco hee Thre Fre, cle tfc on lpia eels oN sa m 1 so conenaton of XN and fs mee ncRPN GP were deine sing LEMS)NAS flog ‘cts tremore conten Pevou esearch Teton tt on ean ntl om aor ove gest arden cre {nen the Fd and Dog Aiton BS) eh ‘Spemi epsie profes ermine thal pos) Se fn of XN and rte for PR tag ‘bat of pr tales ns aaj Yo deerme ‘een af canine owed ha 2 (9 ad ives (10) re primary rset cen 2 congue (ale 2) Th ret wry in XN pln ‘Gncenrann afc cing he 20mg on wl ot Ue roenceof only tae suns of Ome PR osc fer tide ee! ie and ce. Tete, PR ersten were oly dined deat fr the (aan 1D mg 3N does PE paatn for Nad ‘te dled In Ttes 9 ad Thre went dey of ee and gender erica fr XN 60 Tae (0 ~ O08) 1 Tn a ened only he 180 de in me, Male fs f 2N doe were bene for AUC aed {au AVE ip 0000 for a p= 0008 fr 9 ed (Con = 007 fr AM and p< D001 fr DS were Maher ene eve bee 9 fr nnd Bo CU, ij ea be peer nto Foe = {809 tnd Cy eel be Torr Ini ha es (p=. ich nase the 1 mg XN dee {© = 0.05, beens in Ce col partly be a he ear ut ene acs neal Ma ower body ‘eran ae able nated gh deco XN perbdy weigh 180mg NC germ 10g XN pie). The st Tn of Xap ih ing rot ‘imen PE snes fee ee 29) hse ‘omar pa coment rage sd pet ele ‘uma oemal com 252 Cage lea Pk am ort ea ena Horm atc ng een gn) On = oe tr ele werk Som wet ‘ot wot ‘Si ne " aie Bee Soret seer tir tm rma br a 8 vm ns ao dete ete ae” Sy etme 1-2 a ojos wee edit cin ‘ating reali non al jc Leo GPR we ‘dette inal abt esting tht Ose {Fi nota jor tao pay n haa Fe 1 gh ees 0a ah el ek of PN ee ‘oor daring ot caer 2 reent PC stay (3, However ees o BPN wre ery ow ne sje nd tet dein thr Ts beaten ct es PA study a9 which showed PN fran ‘ouhing plane cncntcn of a. Tee ngs ‘rd coer, hh se coded Tor fie wok ‘Sshating alate o XN ete ese 7) fend that 5 of poneropaal momen coming 2 pete uppmen for nal apy we poor PM trodes elon rary oxen Tu, mdb ht Foden ay beste reer, he hey {Spreice PN inne vse pes Ths evorenn es ko een cleaved ih ther favnce nay ‘ol ‘eid repeal nan ond tment ee eg ase eit wth other fon oat ‘ur stay oat 23 Be avenge RN P paler ‘how ssid pli concnttian i Slowing ‘ein abortion maxi or sf Whe conse gd of 20 180 XN (24, The na ‘Suaion mau war rnd Uh he od rd {atime XN pls ees exci tt 4 The ‘cand gral nese XN pl lw tae ‘ewe PA ple fr he 6 mg ene po (20). ower sea PX pfs of mie carmaing he {ing oe sowed cen gadis n XN pls leesendthetnigofteneaneiflr grea among ican ha war nt pret when cating he pe Profle Tee ae rey f ft tat cud een ‘ring the ced cen ap el ld Inna ection oral boron {the genes. Thebiphanesbnpion paternal aber oan nial pd apn fm th Tide slain flowed bys dyed dl ssp de ‘Saori ted XN ta ny hae prepei ‘neti ie, Dolton ste ae ede odie = ie RIE BIS tE me. fe He Br HE Ieee My cosmo nite wt ne tt (92013 Ng tt A Han umitoena oe a8 Paani Got) : Sie eat cams fhe ihc spin pte In {nthe AN PR, XP cues Fi A Bho all pakia pa levels hand eer sa ‘Medone won ehich nate sow commento 3 {eters pda ea. 42. Steady-state plasma concontetions acto thecal af N Pde] PRequations or een sey teens were tlsppealelor Ahead, proceed sone tre cls ‘dy using epee eb pan concent ‘oama Reh eng cca Ka, aan econo ua Patna tal as anne pan con

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