Ameliorative effect of ethanolic extract of roots of Tetracera akara (Burm. f.) Merr. on D-galactosamine induced hepatotoxicity in Wistar rats by downregulation of inflammatory mediators like TNFα, COX-2 and iNOS

Abstract

Tetracera akara, a climbing shrub locally called Nennalvalli or Pattuvalli, is an ethnomedicinal plant used by Kani tribe of Kerala to treat chronic liver disorders and inflammatory conditions.  The present study was aimed to evaluate the hepatoprotective activity of ethanolic extract of roots of Tetracera akara root on D-Galactosamine induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced in Wistar rats by intraperitoneal injection of D-GalN (400 mg/kg in saline) in Wistar rats. Ethanolic extract of T. akara root (TA ETH) was administered to the experimental rats in varying doses of (50, 150 and 300 mg/kg/day), p. o. for 7 days. The hepatoprotective effect was evaluated by the estimation of biochemical markers of hepatic injury, anti-oxidant status of the liver by estimating hepatic catalase, superoxide dismutase, glutathione and malondialdehyde, gene and protein expression level of inflammatory marker genes and histopathological evaluation of experimental animals. Administration of TA ETH (150 and 300 mg/kg) significantly (P ≤0.05) restored the levels of serum bilirubin, protein and other hepatic enzymes almost comparable to the standard drug Silymarin-treated groups. The levels of antioxidant enzymes like SOD and CAT were elevated and lipid peroxidation was inhibited as evident from the reduced levels of MDA. The gene expression studies by quantitative PCR method showed that TA ETH significantly (P ≤0.05) downregulated pro inflammatory cytokines, inflammatory COX-2 genes and upregulated IL 10 gene levels in D-GalN induced liver tissue, which was further confirmed in protein estimation by ELISA method. The histopathological observations were in correlation with the biochemical findings showing the presence of normal hepatic architecture, which further evidenced the hepatoprotective effect of TA ETH. Ethanolic extract of the root of T. akara possesses significant hepatoprotective activity mainly by scavenging reactive free radicals, boosting the endogenous antioxidant system in liver and inhibiting pro-inflammatory mediator like TNF α, COX-2, iNOS and promoting the anti-inflammatory IL 10, thus substantiating the tribal claim.