{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T13:24:38Z","timestamp":1772889878609,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,10,2]],"date-time":"2013-10-02T00:00:00Z","timestamp":1380672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Conophylline (CnP) is a vinca alkaloid purified from a tropical plant and inhibits activation of pancreatic stellate cells. We investigated the effect of CnP on hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>) <jats:italic>in vitro<\/jats:italic>. We also examined whether CnP attenuates hepatic fibrosis <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We examined the effect of CnP on the expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and collagen\u20101, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis and apoptosis in rat <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> and Lx\u20102 cells. We also examined the effect of CnP on hepatic fibrosis induced by thioacetamide (TAA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In rat <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> and Lx\u20102 cells, CnP reduced the expression of \u03b1\u2010<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and collagen\u20101. CnP inhibited <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis induced by serum. CnP also promoted activation of caspase\u20103 and induced apoptosis as assessed by <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> ladder formation and <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> assay. In contrast, CnP did not induce apoptosis in <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>12 cells. We then examined the effect of CnP on TAA\u2010induced cirrhosis. In TAA\u2010treated rats, the surface of the liver was irregular and multiple nodules were observed. Histologically, formation of pseudolobules surrounded by massive fibrous tissues was observed. When CnP was administered together with TAA, the surface of the liver was smooth and liver fibrosis was markedly inhibited. Collagen content was significantly reduced in CnP\u2010treated liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Conophylline suppresses <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> and induces apoptosis <jats:italic>in vitro<\/jats:italic>. CnP also attenuates formation of the liver fibrosis induced by TAA <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12328","type":"journal-article","created":{"date-parts":[[2013,9,11]],"date-time":"2013-09-11T11:51:35Z","timestamp":1378900295000},"page":"1057-1067","source":"Crossref","is-referenced-by-count":23,"title":["Conophylline suppresses hepatic stellate cells and attenuates thioacetamide\u2010induced liver fibrosis in rats"],"prefix":"10.1111","volume":"34","author":[{"given":"Norio","family":"Kubo","sequence":"first","affiliation":[{"name":"Institute for Molecular and Cellular Regulation Gunma University Maebashi Japan"},{"name":"Department of General Surgical Science (Surgery I) Gunma University Graduate School of Medicine Maebashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rie","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of General Medicine National Defense Medical College Tokorozawa 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