The role of gallic acid in liver disease: a review of its phytochemistry, pharmacology, and safety.

BACKGROUND: The development of liver diseases adversely affects global health, emerging as a prominent cause of mortality globally and imposing a significant economic strain on society. Gallic acid (GA) is the natural polyphenol that is present in a variety of plants, fruits, tea, traditional Chinese medicine and so on. PURPOSE: This review was aimed to analyze the available literature on GA with a focus on its mechanism of action. METHODS: Several literature databases were searched, including PubMed, Web of Science, Google Scholar, and Scopus to find relevant research on GA and liver disease over the last decade. RESULTS: Our finding indicate that GA can effectively reduce non-alcoholic liver injury, alcoholic liver disease, hepatic fibrosis, drug-induced liver injury, and liver cancer. GA displays remarkable antioxidant effects by activating nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, the anti-inflammatory mechanism is mainly related to the nuclear factor kappa B (NF-κB) signaling pathway and down-regulating some inflammation-related factors such as interleukin 1 (IL-1), interleukin 6 (IL-6), transforming growth factor-beta (TGF-β) and tumor necrosis factor alpha (TNF-α). GA mitigates non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) through the reduction of lipid accumulation, achieved by modulating the AMP-activated protein kinase (AMPK) signaling pathway. In the context of liver cancer, GA additionally modulates the wnt/β-catenin and JAK/STAT3 signaling pathways, as well as their downstream molecular components. CONCLUSION: In this review, different studies indicate that GA have an excellent protective effect against various liver diseases associated with various signaling pathways.