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Arctigenin (ATG), a natural product isolated from the roots of Arctium lappa L., has been reported to exhibit a variety of biological properties, such as antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. In the present study, the effects of ATG on oxidative stress-induced mitochondrial function and apoptosis in HepG2 and SMMC-7721 human hepatoma cells were investigated. Pre-treatment with ATG significantly reversed the oxidative stress-induced decline in the mitochondrial functions. In particular, ATG prevented t-BHP-induced mitochondrial depolarization, NAD(P)H redox state, and reactive oxygen species (ROS) production in HepG2 cells. Furthermore, the expression of anti-apoptotic proteins Bcl-2, Bcl-xl, and