Pharmacological Studies on the Efficacy of Polyherbal Formulation Dawa ul kurkum in DEN-Induced 2-AAF-Promoted Hepatocellular Carcinoma in Male Wistar Rats

The purpose of this study was to explore the anti-cancer activity and the possible mechanism of Dawa-ul kurkum (Duk) against diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in male Wistar rats. We administered Duk at 3 doses, viz., 75, 150, and 300 mg/kg/day, 2 weeks before the DEN and continued it for 16 weeks. We found that Duk significantly reduced the DEN and 2-AAF induced phenotypical changes in rats and restored the activities of serum markers. Furthermore, Duk counteracted the oxidative stress induced by carcinogens as observed by restoration in the levels of superoxide dismutase (SOD) and catalase (CAT). Duk significantly diminished the levels of malondialdehyde (MDA) in a dose dependent manner and restored the liver microarchitecture as assessed by histopathological studies. The results of immunohistochemical staining showed that Duk inhibited the DEN-induced decrease in the number of cells positive for Bid and Caspase-9. It also reduces the number of cells positive for Cyclin D. This study shows that Duk significantly protects rat liver from hepatocarcinogenesis by regulating oxidative damage and restoring serum markers. The chemopreventive effect of Duk might be through induction of apoptosis.