Induction of antioxidant and detoxifying enzymes by oriental bezoar

Oriental bezoar, a gallstone formed in the gall sac of Bos taurus Linne var. domesticus Gmelin (Bovidae), has been used as an antipyretic, sedative, antispasmodic, and detoxifying drug in oriental medicine. It reportedly has an antioxidative effect; however, its underlying mechanism remains unclear. Therefore, we investigated the effects of oriental bezoar and its main components on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which transcriptionally regulates the gene encoding an antioxidant enzyme, heme oxygenase-1 (HO-1), and detoxifying enzymes glutathione-S-transferase alpha 1 (GSTA1) and quinone oxidoreductase 1 (NQO1) in vitro. Using a dual-luciferase reporter assay and real-time PCR, oriental bezoar and its main constituent bilirubin were shown to induce ARE activity and up-regulate the expression of HO-1, GSTA1, and NQO1 in HepG2 cells in a dose-dependent manner. These results suggest that activation of the Nrf2-ARE pathway is partially involved in the antioxidative effect of oriental bezoar, thus providing a scientific basis for oriental bezoar9s traditional use for detoxification.