Hepatoprotective Effects of Terminalia chebula Fruit Extract against 2-AAF–Induced Hepatic Damage in Albino Mice: Role of MDR1 and COX-2

Abstract

Terminalia chebula extracts were evaluated on 2-acetylaminofluorene (2-AAF)-induced hepatocellular carcinoma in mice. The 25 mg.kg⁻¹ b.w. 2-AAF treatment showed liver aberration and up-regulation of multidrug resistance-1 (MDR1), generation of reactive oxygen species (ROS) and cyclooxygenase-2 (COX-2) expression via phosphorylation of Akt-MAPKs and nuclear translocation of NF-κB. Pre-administration of 50 mg.kg⁻¹ TCE along with 25 mg.kg⁻¹ 2-AAF inhibited the expression of MDR1 by preventing ROS generation and COX-2 expression through Akt and MAPK signaling pathway. T. chebula may overcome the 2-AAF-induced oxidative stress and drug resistance in the hepatic tissue of mice and prevent the possible neoplastic transformation leading to hepatocarcinoma.

KEYWORDS:

• 2-acetylaminofluorine
• reactive oxygen species
• cyclooxygenase-2
• mdr-1