Umbelliferone and daphnetin ameliorate carbon tetrachloride-induced hepatotoxicity in rats via nuclear factor erythroid 2-related factor 2-mediated heme oxygenase-1 expression.

Among various phytochemicals, coumarins comprise a very large class of plant phenolic compounds that have good nutritive value, in addition to their antioxidant effects. The purpose of the present study was to investigate the protective effects of two coumarin derivatives, umbelliferone and daphnetin, against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and elucidate the underlying mechanism. Treatment of rats with either umbelliferone or daphnetin significantly improved the CCl4-induced biochemical alterations. In addition, both compounds alleviated the induced-lipid peroxidation and boosted the antioxidant defense system. Moreover, the investigated compounds attenuated CCl4-induced histopathological alterations of the liver. Finally, umbelliferone and daphnetin induced the nuclear translocation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective heme oxygenase-1 (HO-1). These results suggest that umbelliferone and daphnetin ameliorate oxidative stress-related hepatotoxicity via their ability to augment cellular antioxidant defenses by activating Nrf2-mediated HO-1 expression.