Inhibition of P-glycoprotein leads to improved oral bioavailability of compound K, an anticancer metabolite of red ginseng extract produced by gut microflora.

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Zhen YangMing Hu

Abstract

Ginsenosides are hydrolyzed extensively by gut microflora after oral administration, and their metabolites are pharmacologically active against lung cancer cells. In this study, we measured the metabolism of various ginsenosides by gut microflora and determined the mechanisms responsible for the observed pharmacokinetic behaviors of its active metabolite, Compound K (C-K). The results showed that biotransformation into C-K is the major metabolic pathway of ginsenosides after the oral administration of the red ginseng extract containing both protopanaxadiol and protopanaxatriol ginsenosides. Pharmacokinetic studies in normal mice showed that C-K exhibited low oral bioavailability. To define the mechanisms responsible for this low bioavailability, two P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporine A, were used, and their presence substantially decreased C-K's efflux ratio in Caco-2 cells (from 26.6 to <3) and significantly increased intracellular concentrations (by as much as 40-fold). Similar results were obtained when transcellular transport of C-K was determined using multidrug resistance 1 (MDR1)-overexpressing Madin-Darby canine kidney II cells. In MDR1a/b(-/-) FVB mice, its plasma C(max) and AUC(0-24h) were in...Continue Reading

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Citations

Sep 28, 2012·Journal of Agricultural and Food Chemistry·Bing ZhangZe-Yuan Deng
Feb 22, 2014·Journal of Agricultural and Food Chemistry·Jing-Rong WangZhi-Hong Jiang
Sep 16, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Huinan ZhaoBaojian Wu
Mar 5, 2015·Journal of Agricultural and Food Chemistry·Jing-Rong WangZhi-Hong Jiang
May 17, 2014·Food & Function·Kyoung-Sik HanHarjinder Singh
Dec 25, 2013·Antimicrobial Agents and Chemotherapy·Suresh Kumar GorlaLizbeth Hedstrom
Oct 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhenzhou WangJinping Liu
Mar 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xu ZhangMancang Gu
Feb 8, 2020·Pharmaceutics·Ji-Hyeon JeonIm-Sook Song
Nov 1, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Siyu ChenXiao Han
Jul 31, 2020·Pharmaceutical Development and Technology·Liyan ZhaoYiling Wu
Jul 27, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·En Hyung Kim, Wonnam Kim
Mar 29, 2018·European Journal of Drug Metabolism and Pharmacokinetics·Feng-Ling YuHe Zhu
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Panudda DechwongyaKorbtham Sathirakul
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yun-Yan KuangWei Zhou

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