Tanshinone IIA reduces palmitate-induced apoptosis via inhibition of endoplasmic reticulum stress in HepG2 liver cells

Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Palmitate, a saturated fatty acid, is known to induce toxicity and cell death in various types of cells. Tanshinone IIA (Tan IIA), one of the effective components of the traditional Chinese medicine Danshen, was reported to exhibit a variety of biochemical activities, including amelioration of ER stress-mediated apoptosis in renal preservation. To address the hypothesis that tan IIA attenuates apoptosis and triglycerides (TG) accumulation via reducing ER stress, we studied the effect of tan IIA on experimentally induced ER stress using palmitate in HepG2 cells. Palmitate led to cytotoxicity, TG accumulation, and apoptosis in HepG2 cells and also strongly induced ER stress indicated by increased GRP78, phosphorylation of eIF2 alpha, ATF6, and CHOP. Pretreatment with tan IIA (10 mu m) significantly increased cell viability, decreased apoptotic cell death, and reduced the activity of caspase-3. Meanwhile, tan IIA significantly decreased palmitate-induced TG accumulation. Moreover, tan IIA significantly suppressed the phosphorylation of eIF2 alpha, and inhibited GRP78, ATF6, and CHOP expression. In conclusion, tan IIA protects the HepG2 cells exposed to palmitate partially by inhibiting excessive ER stress, ER stress-induced apoptosis, and hepatic steatosis. Therefore, tan IIA has therapeutic potential in the treatment of NAFLD.