Comparison of the effects of hydroalcoholic extract of Dracocephalum kotschyi and silymarin on diclofenac-induced hepatotoxicity in rats: inflammation signaling HMGB1, NLRP3, IL1B

Background and Objective: Excessive and prolonged use of NSAIDs causes hepatotoxicity. The hydroalcoholic extract of Dracocephalum kotschyi 's anti-inflammatory and antioxidant properties are known. This study investigates the potential of Dracocephalum kotschyi in inhibiting diclofenac hepatotoxicity in rat liver. Materials and Methods : 42 male Wistar rats were divided into 6 groups control, diclofenac, 3 groups of diclofenac + hydroalcoholic extract of Dracocephalum kotschyi , and the diclofenac + silymarin group. The control group did not receive any medication. In the other groups, diclofenac (50 mg/kg) was first injected, then in three groups the hydroalcoholic extract of Dracocephalum kotschyi (HEDK) at doses of 40, 80, and 120, in the last group, silymarin was administered at 100 mg/kg for 7 days. Liver enzymes (ALT, AST, ALP), antioxidant enzyme activities, and inflammatory factors were measured and the histopathological changes were assessed. Results: Diclofenac remarkably increased the levels of ALT, AST, ALP, MDA, IL1-β, NLRP3, and HMGB1 and simultaneously reduced the amount of SOD, CAT, and GPX. Treatment with the HEDK reduced Liver biochemical parameters, inflammatory markers, enhanced antioxidant defense and improved histological outcomes. Conclusion: HEDK, with its antioxidant and anti-inflammatory effects, provided significant liver protection against diclofenac-induced toxicity.