{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:39:36Z","timestamp":1784547576983,"version":"3.55.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u00a0mL\/kg) was evaluated against intragastric-fed PZW (0, 60, 120, 240\u00a0mg\/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-1\u03b2, TNF-\u03b1) 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&amp;amp;E\/Sirius red\/immunohistochemical staining. The expressions of MMP1, TIMP1, IL-6, JAK2, STAT3, p-JAK2, p-STAT3, TGF-\u03b2, Smad2\/3 and p-Smad2\/3 were determined by Western blotting technique.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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-1\u03b2, IL-6, TNF-\u03b1, 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-\u03b2\/Smad2\/3 signaling pathway inhibition favoring MMP1\/TIMP-1 ratio that attenuated collagen deposition and promoted collagen degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PZW alleviated hepatic fibrosis\n                      <jats:italic>in vivo<\/jats:italic>\n                      , primarily by inhibiting collagen accumulation through navigating IL-6\/JAK2\/STAT3 and TGF-\u03b2\/Smad2\/3 signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1667685","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T06:29:32Z","timestamp":1762756172000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tibetan medicine Pa Zhu Wan ameliorates carbon tetrachloride-induced liver fibrosis in rats by regulating the TGF-\u03b2-Smad2\/3 and IL-6\/JAK2\/STAT3 signaling pathways"],"prefix":"10.3389","volume":"16","author":[{"given":"Linlin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tin Wui","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"754098","DOI":"10.3389\/fmolb.2021.754098","article-title":"The hepatoprotective effect of piperine against thioacetamide-induced liver fibrosis in mice: the involvement of miR-17 and TGF-\u03b2\/Smads pathways","volume":"8","author":"Abdelhamid","year":"2021","journal-title":"Front. 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