Ethyl gallate isolated from Gypsophila licentiana Hand. -Mazz reduces the risk of liver injury by modulating the RAS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shanyin Chaihu (Gypsophila licentiana Hand. -Mazz) is a traditional Chinese medicine and possesses a history of use for the treatment of various diseases, including hepatitis. Ethyl gallate (EG), the natural pharmacologically active ingredient of Shanyin Chaihu, exerts obvious pharmacological effects against inflammation. However, the underlying therapeutic mechanisms of EG against ALI remain unknown.

AIM OF THE STUDY: To investigate the role and elucidate the mechanisms of EG in ALI mice underlying by performing an integrated analysis.

METHODS

EG was isolated and identified from Gypsophila licentiana Hand. -Mazz. The effects and action mechanisms of EG on ALI in mice were assessed using H&E staining, DIA proteomics, western blotting, immunohistochemistry, molecular dynamics, CETSA, and immunofluorescence.

RESULTS

The results showed that EG was able to significantly decrease the liver coefficient, reduce the levels of ALT and AST in serum, attenuate the expression levels of ROS, F4/80 and LY6G in liver tissue. EG treatment significantly regulated the alteration of RAS signaling pathway in mice. In addition, EG had a good binding score with RAS. Furthermore, we added RAS agonists (ML-099) to mice and found that the effect of EG on improving liver injury was weakened. The experiment further proved that EG could target RAS.

CONCLUSION

These results suggest that EG has the vigour to alleviate liver injury in mice through RAS signaling. The findings provide a strategy for developing the EG, the compound isolated from Shanyin Chaihu, as a potential therapeutic agent for ALI.