Punicalagin Reversed the Hepatic Injury of Tetrachloromethane by Antioxidation and Enhancement of Autophagy

Hepatic injury is significant in the pathogenesis and development of many types of liver diseases. Punicalagin (PU) is a bioactive antioxidant polyphenol found in pomegranates. To explore its protective effect against carbon tetrachloride (CCl(4))-induced liver injury and the mechanism, Institute of Cancer Research (ICR) mice and L02 cells were used to observe the changes of serum biochemical indicators, histopathological liver structure, cell viability, antioxidative indices, and autophagy-related proteins were assessed. In ICR mice, PU ameliorated the CCl(4)-induced increase of the serum aspartate aminotransferase, alanine aminotransferase, the activity of liver lactate dehydrogenase, and the damage of histopathological structure, and exhibited a hepatoprotective effect against CCl(4). PU attenuated oxidative stress by decreasing the liver malondialdehyde level and increasing the activities of liver superoxide dismutase, glutathione peroxidase, and the expression of the liver nuclear factor E2-related factor (Nrf2) protein. Furthermore, according to the vivo and vitro experiments, PU might activate autophagy through the mediation of the Akt/FOXO3a and P62/Nrf2 signaling pathway. Taken together, these results suggest that PU may protect against CCl(4)-induced liver injury through the upregulation of antioxidative activities and autophagy.