Differential response of antioxidant defense in HepG2 cells on exposure of Livotrit(®), in a concentration dependent manner

Livotrit(®), a polyherbal formulation (Zandu, India) is commonly prescribed for liver health. The present study was undertaken to elucidate possible mechanism of antioxidant potential of Livotrit(®). Livotrit(®) exhibited concentration dependent radical scavenging activity, inhibition of lipid peroxidation as well as activation and gene expression of antioxidant enzymes. Interestingly, lower concentration of Livotrit(®) (0.05%) significantly increased activities and gene expression of catalase, Glutathione reductase (GR) and Gluthathione peroxidase (GPx), while higher concentration of Livotrit(®) (0.5%) significantly increased antioxidant enzyme Heme-oxygenase 1(HO-1) and not catalase (CAT), GR and GPx. Transcription factor, Nuclear factor erythroid 2-related factor 2 (Nrf2) required for expression of catalase, GR, GPx and HO-1 was efficiently translocated into the nucleus at both concentrations. Inspite of this, concentration dependent activation of these enzymes was found to be mediated through miRNAs involved in regulation of their gene expression.