Abstract

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 (CCl4)-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 CCl4-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 CCl4. 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 CCl4-induced liver injury through the upregulation of antioxidative activities and autophagy.

Highlights

  • Liver is an important organ for metabolism of drugs and chemicals, while liver disease has been a major global health problem

  • MTT assay showed that the survival of L02 cells treated with 30 lM CCl4 decreased compared with control group (P < .01) (Fig. 2a)

  • CCl4, a colorless, volatile nonflammable liquid, is a haloalkane widely used in industry and chemical laboratories to produce commercial fats, lacquers, and other organic compounds

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Summary

Introduction

Liver is an important organ for metabolism of drugs and chemicals, while liver disease has been a major global health problem. Some extrahepatic factors, such as alcohol, toxins, and drugs, can lead to liver injury, and liver injury is one of the pathological bases of liver cirrhosis or liver failure.[1] the prevention of liver injury is essential. Searching for phytochemicals extracted from natural food, which can prevent and control liver injury and liver diseases with high efficacy and low toxicity, is of significant interest. We focus primarily on the effect of punicalagin (PU), one of the major polyphenols isolated from pomegran-.

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