[Inhibitory effect of PNS on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis]

Zhongguo Zhong Yao Za Zhi. 2012 Nov;37(22):3486-9.
[Article in Chinese]

Abstract

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.

Method: 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.

Result: 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).

Conclusion: Total saponins of the root and rhizome of panax notoginseng have a significant effect on CYP3A activity in rat livers.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP3A / chemistry
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism*
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Kinetics
  • Liver / chemistry
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Panax notoginseng / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Rhizome / chemistry
  • Saponins / chemistry
  • Saponins / pharmacology*

Substances

  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Saponins
  • Cytochrome P-450 CYP3A