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The present study was to evaluate the antifibrogenesis effect of paeonol and involved mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The degree of liver injury was evaluated biochemically by measuring serum and fibrotic markers and pathological examination. Cell viability was evaluated by 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide assay and trypan blue staining. Cytotoxic effects were determined using lactate dehydrogenase release assay. Cell cycle was determined using single dyeing methods of propidium iodide (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>) by flow cytometry. Apoptosis was confirmed using double\u2010staining of annexin <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>oechst. <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blot, immunofluorescence and real\u2010time polymerase chain reaction were used to explore the molecular mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with paeonol significantly protected the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, improving the histological architecture of the liver, and by inhibiting activation of hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content>) in vivo. Interestingly, paeonol had no apparent cytotoxic effects but could markedly inhibit primary <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> proliferation and induced <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> cell cycle arrest at the <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>2\/<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content> checkpoint. These effects were caused by paeonol suppression of phosphorylation of cycle protein cdc2 and of <jats:styled-content style=\"fixed-case\">CDK<\/jats:styled-content>2. Moreover, that paeonol triggered mitochondrial apoptosis pathway and led to activation of caspase cascades in <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> was found. Mechanistic investigations revealed that the nuclear factor\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>) pathway inhibition resulted in the earlier events. Furthermore, paeonol altered the expression of some marker proteins relevant to <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content> activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Paeonol could inhibit <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content> proliferation and induce mitochondrial apoptosis via disrupting <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> pathway, which might be the mechanisms of paeonol reduction of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12147","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T07:58:58Z","timestamp":1361433538000},"page":"1223-1233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Paeonol inhibits hepatic fibrogenesis via disrupting nuclear factor\u2010\u03ba<scp>B<\/scp> pathway in activated stellate cells: In vivo and in vitro studies"],"prefix":"10.1111","volume":"28","author":[{"given":"Desong","family":"Kong","sequence":"first","affiliation":[{"name":"National First\u2010Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"National First\u2010Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghua","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Chinese Materia Medica and Pharmaceutical Botany College of Pharmacy Daqing Branch of Harbin Medical University  Daqing 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