Research Paper Volume 16, Issue 5 pp 4759—4777
Network pharmacology and transcriptomic profiling elucidate the therapeutic effects of Ranunculus ternatus Thunb on liver fibrosis via MK3-NF-κB inhibition
- 1 Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China
- 2 Department of Gastroenterology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
- 3 Department of Cardiology, Guiqian International General Hospital, Guiyang, Guizhou Province, China
- 4 Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
Received: October 24, 2023 Accepted: January 23, 2024 Published: March 8, 2024
https://doi.org/10.18632/aging.205629How to Cite
Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of β-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with β-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of β-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of β-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas β-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of β-sitosterol in the treatment of liver fibrosis, suggesting that β-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.