{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:47:13Z","timestamp":1790282833612,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T00:00:00Z","timestamp":1475539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Liver fibrosis is one of the leading causes of morbidity and mortality worldwide with very limited therapeutic options. Given the pivotal role of activated hepatic stellate cells in liver fibrosis, attention has been directed towards the signalling pathways underlying their activation and fibrogenic functions. Recently, the hedgehog (Hh) signalling pathway has been identified as a potentially important therapeutic target in liver fibrosis. The present study was designed to explore the antifibrotic effects of the potent Hh signalling inhibitor, forskolin, and the possible molecular mechanisms underlying these effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male Sprague\u2010Dawley rats were treated with either CCl<jats:sub>4<\/jats:sub> and\/or forskolin for 6 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed. Hepatic fibrosis was assessed by measuring \u03b1\u2010SMA expression and collagen deposition by Masson's trichrome staining and hydroxyproline content. The effects of forskolin on oxidative stress markers (GSH, GPx, lipid peroxides), inflammatory markers (NF\u2010\u03baB, TNF\u2010\u03b1, COX\u20102, IL\u20101\u03b2), TGF\u2010\u03b21 and Hh signalling markers (Ptch\u20101, Smo, Gli\u20102) were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Hepatic fibrosis induced by CCl<jats:sub>4<\/jats:sub> was significantly reduced by forskolin, as indicated by decreased \u03b1\u2010SMA expression and collagen deposition. Forskolin co\u2010treatment significantly attenuated oxidative stress and inflammation, reduced TGF\u2010\u03b21 levels and down\u2010regulated mRNA expression of Ptch\u20101, Smo and Gli\u20102 through cAMP\u2010dependent PKA activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>In our model, forskolin exerted promising antifibrotic effects which could be partly attributed to its antioxidant and anti\u2010inflammatory effects, as well as to its inhibition of Hh signalling, mediated by cAMP\u2013dependent activation of PKA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13611","type":"journal-article","created":{"date-parts":[[2016,9,3]],"date-time":"2016-09-03T02:13:18Z","timestamp":1472868798000},"page":"3248-3260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Forskolin, a hedgehog signalling inhibitor, attenuates carbon tetrachloride\u2010induced liver fibrosis in 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