The inhibitory effect of intestinal bacterial metabolite of ginsenosides on CYP3A activity.
The intestinal bacterial metabolites of ginsenosides are responsible for the main pharmacological activities of ginseng. The purpose of this study was to find whether these metabolites influence hepatic metabolic enzymes and to predict the potential for ginseng-prescription drug interactions. Utilizing the probe reaction of CYP3A activity, testosterone 6beta-hydroxylation, the effects of derivatives of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol families on CYP3A activity in rat liver microsomes were assayed. Our results showed that ginsenosides from the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol family including Rb1, Rb2, Rc, Compound-K, Re, and Rg1 had no inhibitory effect, whereas Rg2, 20(S)-panaxatriol and 20(S)-protopanaxatriol exhibited competitive inhibitory activity against CYP3A activity in these microsomes with the inhibition constants (Ki) of 86.4+/-0.8 microM, 1.7+/-0.1 microM, and 3.2+/-0.2 microM, respectively. This finding demonstrates that differences in their chemical structure might influence the effects of ginsenosides on CYP3A activity and that ginseng-derived products might have potential for significant ginseng-drug interactions.
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, PR China.
Yong
Y
Liu
Wei
W
Li
Peng
P
Li
Mai-Cun
MC
Deng
Sheng-Li
SL
Yang
Ling
L
Yang
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001419:Bacteria / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D004365:Drugs, Chinese Herbal / Q000378:metabolism; D036145:Ginsenosides / Q000378:metabolism*; D006900:Hydroxylation; D006915:Hydroxytestosterones / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000378:metabolism / Q000494:pharmacology*; D014315:Triterpenes / Q000378:metabolism / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D006915:Hydroxytestosterones; D012502:Sapogenins; D014315:Triterpenes; C081552:protopanaxatriol; C025591:6 beta-hydroxytestosterone; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; C062916:protopanaxadiol