Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl(4)-intoxicated mice

Toxicology. 2011 Feb 4;280(1-2):33-43. doi: 10.1016/j.tox.2010.11.005. Epub 2010 Nov 21.

Abstract

This study investigated the protective effects of isoquinoline alkaloid berberine on the CCl(4)-induced hepatotoxicity in mice. Berberine was administered as a single dose at 5 and 10mg/kg intraperitoneally (i.p.), 1h before CCl(4) (10%, v/v in olive oil, 2ml/kg) injection and mice were euthanized 24h later. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl(4)-intoxicated mice was markedly suppressed by berberine in a concentration-dependent manner. The decrease in hepatic activity of superoxide dismutase (Cu/Zn SOD) and an increase in lipid peroxidation were significantly prevented by berberine. Histopathological changes were reduced and the expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was markedly attenuated by berberine 10mg/mg. The results of this study indicate that berberine could be effective in protecting the liver from acute CCl(4)-induced injury. The hepatoprotective mechanisms of berberine may be related to the free radical scavenging and attenuation of oxidative/nitrosative stress, as well as to the inhibition of inflammatory response in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Berberine / pharmacology*
  • Carbon Tetrachloride / toxicity
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / genetics
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cyclooxygenase 2 Inhibitors
  • Tumor Necrosis Factor-alpha
  • Berberine
  • Carbon Tetrachloride
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Superoxide Dismutase
  • Alanine Transaminase
  • Alkaline Phosphatase