Research Paper Volume 12, Issue 11 pp 10614—10632

Ursolic acid reverses liver fibrosis by inhibiting interactive NOX4/ROS and RhoA/ROCK1 signalling pathways

Sizhe Wan1, *, , Fangyun Luo1, *, , Chenkai Huang1, , Cong Liu1, , Qingtian Luo1, , Xuan Zhu1, ,

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
* Equal contribution

Received: February 13, 2020       Accepted: April 20, 2020       Published: June 3, 2020
How to Cite

Copyright © 2020 Wan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Liver fibrosis is the reversible deposition of extracellular matrix (ECM) and scar formation after liver damage by various stimuli. The interaction between NOX4/ROS and RhoA/ROCK1 in liver fibrosis is not yet clear. Ursolic acid (UA) is a traditional Chinese medicine with anti-fibrotic effects, but the molecular mechanism underlying these effects is still unclear. We investigated the interaction between NOX4/ROS and RhoA/ROCK1 during liver fibrosis and whether these molecules are targets for the anti-fibrotic effects of UA. First, we confirmed that UA reversed CCl4-induced liver fibrosis. In the NOX4 intervention and RhoA intervention groups, related experimental analyses confirmed the decrease in CCl4-induced liver fibrosis. Next, we determined that the expression of NOX4 and RhoA/ROCK1 was decreased in UA-treated liver fibrotic mice. Furthermore, RhoA/ROCK1 expression was decreased in the NOX4 intervention group, but there was no significant change in the expression of NOX4 in the RhoA intervention group. Finally, we found that liver fibrotic mice showed a decline in their microbiota diversity and abundance, a change in their microbiota composition, and a reduction in the number of potential beneficial bacteria. However, in UA-treated liver fibrotic mice, the microbiota dysbiosis was ameliorated. In conclusion, the NOX4/ROS and RhoA/ROCK1 signalling pathways are closely linked to the development of liver fibrosis. UA can reverse liver fibrosis by inhibiting the NOX4/ROS and RhoA/ROCK1 signalling pathways, which may interact with each other.


ECM: extracellular matrix; UA: ursolic acid; AP: apocynin; FA: fasudil; HSCs: hepatic stellate cells; NOX: NADPH oxidase; ROS: reactive oxygen species; MFBs: myofibroblasts; CCl4: carbon tetrachloride; AAV: adeno-associated virus; ALT: aminotransferase; AST: aspartate aminotransferase; TBIL: total bilirubin; MDA: malondialdehyde.