Influence of ginsenoside Rh1 and F1 on human cytochrome p450 enzymes.
For an oral herbal medicine, the components that can enter the systemic circulation may be the really effective components. In the present study, the effects on the human cytochrome P450 activities of ginsenoside Rb (1) and two hydrolysis products of 20( S)-protopanaxatriol ginsenosides in humans, namely ginsenoside Rh (1) and F (1), which may reach the systemic circulation after oral administration of ginseng extract, were evaluated. Our results showed that Rb (1) exhibited no marked effects on the activities of human cytochrome P450, whereas Rh (1) and F (1) exhibited competitive inhibition of the activity of CYP3A4 with K(i) values of 57.7 +/- 9.6 microM and 67.8 +/- 16.2 microM, respectively. F (1) also exhibited a weaker inhibition of the activity of CYP2D6. Rh (1) exhibited a weak stimulation rather than an inhibition of the activity of CYP2E1. The degradation of ginsenosides in the gastrointestinal tract may play an important role in the ginseng-associated drug-drug interactions, but the effects might be not due to Rh (1) and F (1).
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, 457 Zhong-shan Road, Dalian 116023, P. R. China.
Yong
Y
Liu
Hong
H
Ma
Jiang-Wei
JW
Zhang
Mai-Cun
MC
Deng
Ling
L
Yang
D000328:Adult; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D036145:Ginsenosides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D005894:Panax / Q000737:chemistry
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D036145:Ginsenosides; C055327:ginsenoside F1; C425564:ginsenoside Rh1; D003577:Cytochrome P-450 Enzyme System