Hepatoprotective activity of the neem-based constituent azadirachtin-A in carbon tetrachloride intoxicated Wistar rats

Can J Physiol Pharmacol. 2014 Apr;92(4):267-77. doi: 10.1139/cjpp-2013-0449. Epub 2014 Jan 9.


The aim of this study was to investigate the hepatoprotective role of azadirachtin-A in carbon tetrachloride (CCl4) induced hepatotoxicity in rats. The group allotment for the animals used in the hepatoprotective study included a vehicle treatment group, CCl4 (1 mL · (kg body mass)(-1)) treatment group, silymarin (100 μg · (kg body mass)(-1) · day(-1)) + CCl4 treatment group, and groups treated with different doses of azadirachtin-A (100 or 200 μg · (kg body mass)(-1) · day(-1)) + CCl4. On the 9th day, blood was obtained for measuring the biochemical parameters, and liver tissue was obtained for pathological examination. The acute toxicity test with azadirachtin-A (500, 1000, or 2000 μg · (kg body mass)(-1)) indicated no mortality after 14 days of treatment; further, there was no change in behavior, food consumption, or organ mass. However with the higher dose, some hematological parameters showed changes. Hepatoprotective studies revealed that the CCl4 treatment group exhibited a decrease in total protein and albumin levels, whereas a significant increase in BUN, AST, ALT, and ALP levels were noticed compared with the vehicle-treated control, indicating that there was liver damage caused by CCl4. Histology and ultrastructure study confirmed that pretreatment with azadirachtin-A dose-dependently reduced hepatocellular necrosis and, therefore, protected the liver against toxicity caused by CCl4. The results from this study indicate that pretreatment with azadirachtin-A at the higher dose levels, moderately restores the rat liver to normal. This study confirms that azadirachtin-A possesses greater hepatoprotective action; however, the effective concentration needs to be determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azadirachta / chemistry*
  • Carbon Tetrachloride*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / pathology
  • Female
  • Limonins / chemistry
  • Limonins / therapeutic use*
  • Liver / blood supply
  • Liver / pathology*
  • Male
  • Necrosis
  • Phytotherapy
  • Rats
  • Rats, Wistar


  • Limonins
  • Carbon Tetrachloride
  • azadirachtin