title: Deglycosylated ginsenosides are more potent inducers of CYP1A1, CYP1A2 and CYP3A4 expression in HepG2 cells than glycosylated ginsenosides.
abstract: Ginseng is one of the most commonly used herbal medicines worldwide. Ginsenosides are believed to be responsible for the therapeutic activities of ginseng; however, co-administration of prescription drugs with ginseng products may give rise to ginseng-drug interactions. Cytochrome P450 enzymes are major phase I enzymes involved in the metabolism of most currently used drugs. Inhibition or induction of P450 enzymes can lead to pharmacokinetic drug interactions. Previous reports on ginseng-drug interactions have been controversial and confusing. In the present study, we examined the effects of thirteen ginsenosides on the expression of CYP1A1, CYP1A2 and CYP3A4 in HepG2 cells. We found that eight ginsenosides and aglycones potently induced CYP1A1 expression, and that structure-activity relationships existed for these effects. Moreover, we discovered that deglycosylated ginsenosides, some of which are putative ginsenoside metabolites, were more potent inducers of CYP1A1, CYP1A2 and CYP3A4 than glycosylated ginsenosides. This finding indicates that ginsenoside metabolites may partially account for ginseng-drug interactions, and that differences in the composition of intestinal bacteria and the extent of deglycosylation of the ginsenosides could be a contributing factor to the inconsistencies observed in previous clinical and pre-clinical studies with regard to ginseng-drug interactions.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Graduate School of the Chinese Academy of Sciences, Sanghai, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Hao
authors.forename: Qian
authors.initials: Q
authors.lastname: Ba
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Jingquan
authors.initials: J
authors.lastname: Li
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects*; D036145:Ginsenosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006031:Glycosylation; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D005894:Panax / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D036145:Ginsenosides; D010936:Plant Extracts; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human