Pharmacological research progress of ursolic acid for the treatment of liver diseases

Ursolic acid is a natural pentacyclic triterpenoid with various pharmacological activities such as anti-inflammatory, hepatoprotective, antitumor, and hypoglycemic activity. This natural product is widely present in many common Chinese herbal medicines such as Hedyotis diffusa and Prunella vulgaris. The present review highlights the pharmacological research progress of ursolic acid in liver disease, with a focus on providing directions for future research and clinical practice of ursolic acid. Modern studies have demonstrated that ursolic acid can adjust the activities of enzymes such as superoxide dismutase and NADPH oxidase to balance oxidative stress, reduce inflammation, as well as to repair damaged liver. Research also showed that ursolic acid targeted lipid metabolic genes, activating autophagy and reducing lipid deposition in hepatocytes, further preventing the progress of fatty liver. Besides, the combination of ursolic acid with caspase-3 was able to prevent apoptosis and relieve liver injury. Furthermore, ursolic acid was showed to target the intestine by alleviating mucosal injury and restoring the balance of the intestinal microecology and protect liver through the enterohepatic axis. In terms of antitumor activity, ursolic acid targeted several tumor suppressor genes including gene of phosphate and tension homology deleted on chromsome ten and p53, and affected the expression of cyclin and apoptosis-related proteins involving Bax, Bcl-2, and Bcl-x, which acted on signal transduction pathways including phosphatidylinositol-3-kinase/protein kinase B, extracellular regulated protein kinases and proteina fosforilata 21 wide-type actiated factorlp 1. The same compound interacted with caspases, resulting in inhibition of cell proliferation and induction of apoptosis. In addition, ursolic acid also exerted anticancer activity through inhibiting angiogenesis, tumor invasion and metastasis, and improving immunity. Other studies have noted the importance of nano-preparations of ursolic acid for its clinical applications. This review provides essential information on the role of ursolic acid in liver protection. Further research on the mechanisms of action of ursolic acid would be useful for its pharmaceutical development and clinical application