Inhibitory effects of Citrus unshiu pericarpium extracts on palmitate-induced lipotoxicity in HepG2 cells

Citrus unshiu pericarpium (CP), a rich source of flavonoids, has been used as a traditional medicine for purposes of exhaustion, cold, and cancer treatment in East Asia including China and Korea. This study investigated the effect of CP extracts on palmitate-induced lipotoxicity in hepatocytes, HepG2. Cell viability and apoptosis were measured by Tryphan blue staining and Hoechst staining, respectively. Cellular uptake of free fatty acid was measured by Oil Red 0 staining. The results show that CP extracts attenuated palmitate-induced intracellular lipid accumulation and lipotoxicity in HepG2 cells. CP extracts also blocked the expression of apo B protein; an apolipoprotein with functional roles in intracellular lipid accumulation. Moreover, CP extracts inhibited the release of the mitochondrial cytochrome c through regulation of apoptosis-related proteins, Bax and Bcl-2. These results demonstrated a novel function of CP extracts in preventing lipotoxicity in HepG2 cells, implicating a promising phytotherapeutic approach for lipo-detoxification.