Suppression of Hepatic Cyp1a2 by Total Ginsenosides in Lipopolysaccharide-Treated Mice and Primary Mouse Hepatocytes

J Agric Food Chem. 2016 Mar 23;64(11):2386-93. doi: 10.1021/acs.jafc.5b06170. Epub 2016 Mar 9.

Abstract

The roots of Panax ginseng (ginseng) have been extensively used in traditional Chinese medicine. However, herb-drug interactions between ginseng and other co-administered drugs are not fully understood concerning the effect of ginseng on drug metabolism and clearance. The current study aimed to elucidate the effect of total ginsenosides, a typical ginseng extract, on the regulation of Cyp1a2, a key enzyme to regulate drug metabolism under the normal and inflammatory conditions in mice. Female C57BL/6J mice treated with vehicle and lipopolysaccharide (LPS) were intragastrically administered ginseng extract for 7 days before hepatic P450 expression was analyzed. Primary mouse hepatocytes were also employed to further explore the effects of total ginsenosides on Cyp1a2 expression. The results showed that total ginsenosides in P. ginseng extract exhibited a concentration-dependent suppression on Cyp1a2 mRNA and protein level in both mice and primary mouse hepatocytes. Notably, the inhibitory effects of total ginsenosides on Cyp1a2 mRNA and protein expression were further enhanced following LPS treatment. Therefore, future research is warranted to investigate the role of ginsenosides in the regulation of hepatic CYP450s. Moreover, consumption of ginseng as food or supplement should be monitored for patients on combinational therapy, especially those with inflammatory diseases.

Keywords: C57BL/6J mice; Cyp1a2; ginsenosides; lipopolysaccharide; murine primary hepatocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A2 / analysis
  • Cytochrome P-450 CYP1A2 / drug effects*
  • Cytochrome P-450 CYP1A2 / genetics
  • Female
  • Gene Expression / drug effects
  • Ginsenosides / pharmacology*
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology*
  • Lipopolysaccharides / pharmacology*
  • Liver / enzymology*
  • Mice
  • Mice, Inbred C57BL
  • Panax / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • RNA, Messenger / analysis

Substances

  • Ginsenosides
  • Lipopolysaccharides
  • Plant Extracts
  • RNA, Messenger
  • Cytochrome P-450 CYP1A2