{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T05:17:51Z","timestamp":1737695871357,"version":"3.33.0"},"reference-count":38,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>We investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the oxidative metabolism of valproic acid (VPA) in hepatic microsomes from donors with the CYP2C9*1\/*1 genotype. G. biloba extract decreased 4-ene-VPA, 3-OH-VPA, 4-OH-VPA, and 5-OH-VPA formation with mean\u00a0(\u00b1 SE) IC<jats:sub>50<\/jats:sub>values of 340\u00a0\u00b1 40\u00a0\u03bcg\/mL, 370\u00a0\u00b1 100\u00a0\u03bcg\/mL, 180\u00a0\u00b1 30\u00a0\u03bcg\/mL, and 210\u00a0\u00b1 20\u00a0\u03bcg\/mL, respectively. This was associated with inhibition of not only CYP2C9*1, but also CYP2A6 and CYP2B6. Bilobalide, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, quercetin-3-O-rutinoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-rutinoside were not responsible for the inhibition of VPA metabolism by the extract. When analyzed as the sum of the aglycone and total glycosides present in the extract, quercetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 76%, 51%, and 70%, respectively, kaempferol decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 65%, 46%, and 49%, respectively, and isorhamnetin decreased 4-ene-VPA, 4-OH-VPA, and 5-OH-VPA formation by 29%, 26%, and 31%, respectively. The 3\u00a0aglycones did not affect 3-OH-VPA formation. In summary, G. biloba extract decreased hepatic microsomal formation of 4-ene-VPA, 4-OH-VPA, 5-OH-VPA, and 3-OH-VPA, but the effect was not due to the terpene trilactones or flavonol glycosides investigated in our study.<\/jats:p>","DOI":"10.1139\/y06-085","type":"journal-article","created":{"date-parts":[[2007,12,7]],"date-time":"2007-12-07T16:16:55Z","timestamp":1197044215000},"page":"848-855","source":"Crossref","is-referenced-by-count":11,"title":["Effect of Ginkgo biloba extract on oxidative metabolism of valproic acid in hepatic microsomes from donors with the<i>CYP2C9*1\/*1<\/i>genotypeThis article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products."],"prefix":"10.1139","volume":"85","author":[{"given":"Andrew M.","family":"Numa","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank S.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas K.H.","family":"Chang","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"atypb1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)00161-4"},{"key":"atypb2\/ref2","doi-asserted-by":"publisher","DOI":"10.1021\/tx00004a001"},{"key":"atypb3\/ref3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1212\/WNL.46.2.465","volume":"46","author":"Bryant A.E.","year":"1996","journal-title":"Neurology"},{"key":"atypb4\/ref4","first-page":"5629","volume":"53","author":"Chang T.K.H.","year":"1993","journal-title":"Cancer Res."},{"key":"atypb5\/ref5","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1124\/dmd.105.005751","volume":"34","author":"Chang T.K.H.","year":"2006","journal-title":"Drug Metab. 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