Hepatoprotection in a rat model of acute liver damage through inhibition of CY2E1 activity by total alkaloids extracted from Rubus alceifolius Poir

Int J Toxicol. 2011 Mar;30(2):237-43. doi: 10.1177/1091581810390711. Epub 2011 Jan 11.

Abstract

We aimed to examine the effect of an alkaloid extract of the roots of Rubus alceifolius Poir on liver damage and cytochrome enzymes, and underlying mechanism. Hepatotoxicity was induced in rats by treatment with carbon tetrachloride (CCl(4)). Rats were then treated with the hepatoprotective drug bifendate, or with low, medium, and high doses of an alkaloid extract from the roots of R alceifolius Poir. Both bifendate and alkaloid treatment decreased the increase in liver enzymes and cell damage caused by CCl(4). Carbon tetrachloride treatment alone caused a decrease in total cytochrome P450 content, an increase in CYP2E1 and CYP3A1 messenger RNA (mRNA) levels, and an increase in CYP2E1 and a decrease in CYP3A1 enzymatic activity. Alkaloid treatment brought these concentrations and activities back toward normal. In summary, these results suggest that alkaloids from R alceifolius Poir may act to protect the liver through decreasing CYP2E1 enzymatic activity through decreasing its mRNA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Biomarkers
  • Biphenyl Compounds / pharmacology
  • Carbon Tetrachloride / toxicity
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism
  • Female
  • Male
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • Protective Agents / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rosaceae / chemistry*

Substances

  • Alkaloids
  • Biomarkers
  • Biphenyl Compounds
  • Plant Extracts
  • Protective Agents
  • RNA, Messenger
  • bifendate
  • Carbon Tetrachloride
  • Cytochrome P-450 CYP2E1