Antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica and its bioactive component ellagic acid against diclofenac induced oxidative stress and hepatotoxicity

Long term usage and overdose of diclofenac (DCF), an anti-inflammatory drug is known to cause oxidative stress and liver injury. The present study reports the antioxidant, anti-inflammatory and hepatoprotective activities of Terminalia bellirica (Tb) fruit aqueous and ethyl acetate extracts and its bioactive compound ellagic acid (EA) against DCF-induced toxicity. in vitro antioxidant activities were measured by ABTS and FRAP assays while anti‐inflammatory activity was assessed by the albumin denaturation method. The adverse effects of DCF and hepatoprotective potential of Tb extracts and EA were assessed in serum and liver tissue of rats after oral administration for 21 days. Silymarin was used as standard hepatoprptective agent for comparison. Hepatic markers analyzed in serum included ALP, GPT, GOT, LDH, γ-glutamyl transferase, total protein, creatinine, and uric acid while superoxide dismutase (SOD) and catalase (CAT) were analyzed in liver tissue. The EA exhibited superior ABTS radical scavenging, FRAP, and anti-inflammatory activities as compared to fruit extracts. DCF treatment led to rise in the levels of most of the serum hepatic markers with decline in total serum protein as well as SOD and CAT in liver tissue. The supplementation of extracts, EA and silymarin in DCF treated rats significantly reduced the adverse effects of DCF on serum and tissue markers. Histopathology of the liver indicated that extracts and EA significantly decreased the degree of liver fibrosis. The hepatoprotective ability of EA was comparable to the silymarin but activity of Tb fruit extracts was little lower. Among fruit extracts ethyl acetate extract exhibited better activity than aqueous extract. The results revealed that ellagic acid and T. bellirica fruit extracts have potential to mitigate oxidative stress and hepatotoxicity produced by long term use of diclofenac.