[Inhibitory effect of PNS on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis].
OBJECTIVE
To study the inhibitory effect of total saponins of the root and rhizome of Panax notoginseng (PNS) on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis.


METHODS
Microsome enzyme was prepared by differential velocity centrifugation. Michaelis constant (Km) and maximum velocity (Vmax) of CYP3A, 50% inhibitory concentration of PNS on CYP3A, and the inhibition type and the inhibition constant of CYP3A (Ki, Kis) of PNS on CYP3A were calculated by Lineweaver-Burk and the low of semi-effect-probit.


RESULTS
Total saponins of the root and rhizome of panax notoginseng inhibited CYP3A activity, with IC50 of 689.54 mg x L(-1). Compared with the substrate aminopyrine, CYP3A showed Km of 0.036 mmol x L(-1) and Vmax of 21.01 micromol min(-1) x g(-1). Total saponins of the root and rhizome of panax notoginseng showed a mixed inhibition on CYP3A, with the inhibition constants of 247.79 mg x L(-1) (Ki) and 321.79 mg x L(-1) (Kis).


CONCLUSIONS
Total saponins of the root and rhizome of panax notoginseng have a significant effect on CYP3A activity in rat livers.
Department of Pharmacology, Faculty of Pharmacy, Guangxi Traditional Chinese Medical University, Nanning 530001, China.
Zi-Ming
ZM
Yang
Xiu-Fen
XF
Yang
D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D053723:Panax notoginseng / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*
D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D012503:Saponins; D051544:Cytochrome P-450 CYP3A