ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1667685
Tibetan medicine Pa Zhu Wan ameliorates carbon tetrachloride-induced liver fibrosis in rats by regulating the TGF-β-Smad2/3 and IL-6/JAK2/STAT3 signaling pathways
Provisionally accepted
- 1Qinghai University, Xining, China
- 2Xining First People's Hospital, Xining, China
- 3Universiti Teknologi MARA Puncak Alam, Selangor, Malaysia
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Background: Pa Zhu Wan (PZW) is a Tibetan medicine with natural actives potentially for liver fibrosis treatment. This study determines the therapeutical effects and mechanisms of actions of PZW on carbon tetrachloride-induced hepatic fibrosis in rats. Methods: The chemical profiles of PZW and its serum metabolites were assessed. The liver elasticity of rats with hepatic fibrosis (induced by carbon tetrachloride-olive oil mixture 1:3 v/v, 0.5 mL/kg) was evaluated against intragastric-fed PZW (0, 60, 120, 240 mg/kg body weight daily for 8 weeks) vs ursodeoxycholic acid (positive control) with normal rats as negative control by shear wave elastography system (n = 8/group). The serum aminotransferase (ALT and AST), alkaline phosphatase (ALP), bilirubin (TBIL and DBIL), bile acid, inflammatory cytokines (IL-6, IL-1β, TNF-α) and liver fibrosis indicator (HA, LN, PC-III and IV-C) concentrations were measured by ELISA kits. Pathological changes and collagen deposition extent of liver were characterized by immunoassay and H&E/Sirius red/immunohistochemical staining. The expressions of MMP1, TIMP1, IL-6, JAK2, STAT3, p-JAK2, p-STAT3, TGF-β, Smad2/3 and p-Smad2/3 were determined by western blotting technique. Results: Piperine, trehalose, mulberroside F, chebulic acid, gallic acid and hydroxysafflor yellow A were main compounds of PZW. PZW alleviated liver fibrosis in a dose-dependent manner with reduced fibrous connective tissue/collagen, pseudolobules and inflammatory cell infiltration. The serum IL-1β, IL-6, TNF-α, TBIL, DBIL, ALT, AST and ALP levels decreased with rats treated with PZW where reduced liver inflammation halted its fibrosis and improved overall hepatic health. PZW mitigated hepatic fibrosis in association with IL-6/JAK2/STAT3 and TGF-β/Smad2/3 signaling pathway inhibition favoring MMP1/TIMP-1 ratio that attenuated collagen deposition and promoted collagen degradation. Conclusion: PZW alleviated hepatic fibrosis in vivo, primarily by inhibiting collagen accumulation through navigating IL-6/JAK2/STAT3 and TGF-β/Smad2/3 signaling pathways.
Keywords: Collagen, Inflammation, IL-6/JAK2/STAT3, liver fibrosis, Pa Zhu Wan, TGF-β-smad2/3
Received: 17 Jul 2025; Accepted: 07 Oct 2025.
Copyright: © 2025 Zhao, Jiang, Ma, Yong, Liu, Wang, Wong and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tin Wui Wong, wongtinwui@uitm.edu.my
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