Protective effect of andrographolide against concanavalin A-induced liver injury

Naunyn Schmiedebergs Arch Pharmacol. 2012 Jan;385(1):69-79. doi: 10.1007/s00210-011-0685-z. Epub 2011 Sep 24.

Abstract

This study was designed to investigate the hepatic protective effect and the molecular mechanisms of andrographolide in concanavalin A-induced liver injury model. Results showed that andrographolide (Ag) attenuated concanavalin A (Con-A)-induced liver injury and inhibited hepatocyte apoptosis. Further results showed that oxidative stress response genes were significantly elevated during the pathogenesis induced by Con-A. Meanwhile, gadolinium chloride and N-acetyl-L-cysteine (NAC) treatment, which inactivates Kupffer cells or reduces reactive oxygen species, respectively, prevented the liver injury. So the messenger RNA levels of the oxidative response genes mentioned above were detected, and the following results showed that Ag treatment reduced their expression. Besides, serum lactate dehydrogenase and myeloperoxidase activity was significantly reduced by Ag. Finally, Ag treatment did not further reduce serum tumor necrosis factor-α production compared with NAC treatment alone. Thus, our results indicate that Ag prevents Con-A-induced liver injury and reduced the hepatic oxidative stress response. The hepatic protective effect of Ag indicates that Ag supplementation may be beneficial in the treatment of immune-mediated liver injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Concanavalin A / toxicity*
  • Cyclooxygenase 2 / genetics
  • DNA Fragmentation / drug effects
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Glucose Transporter Type 1 / genetics
  • Heme Oxygenase-1 / genetics
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • L-Lactate Dehydrogenase / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / blood
  • Nitric Oxide Synthase Type II / genetics
  • Oxidative Stress / drug effects
  • Peroxidase / blood
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • RNA, Messenger / metabolism
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Diterpenes
  • Glucose Transporter Type 1
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Protective Agents
  • RNA, Messenger
  • Slc2a1 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • andrographolide
  • L-Lactate Dehydrogenase
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase-1
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1