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The transcription factor glioma\u2010associated oncogene homologue 1 (GLI1) is a potentially important therapeutic target in liver fibrosis. This study investigates the anti\u2010fibrotic activities and potential mechanisms of the phytochemical, physalin B.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Two mouse models (CCl<jats:sub>4<\/jats:sub> challenge and bile duct ligation) were used to assess antifibrotic effects of physalin B in vivo. Mouse primary hepatic stellate cells (pHSCs) and human HSC line LX\u20102 also served as in vitro liver fibrosis models. Liver fibrogenic genes, GLI1 and GLI1 downstream genes were examined using Western blot and quantitative real\u2010time PCR (qRT\u2010PCR). GLI1 acetylation and LAP2\u03b1\u2013HDAC1 interaction were analysed by co\u2010immunoprecipitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In vivo, physalin B administration attenuated hepatic histopathological injury and collagen accumulation and decreased expression of fibrogenic genes. Physalin B dose\u2010dependently suppressed fibrotic marker expression in LX\u20102 cells and mouse pHSCs. Mechanistic studies showed that physalin B inhibited GLI activity by non\u2010canonical Hedgehog signalling. Physalin B blocked formation of lamina\u2010associated polypeptide 2\u03b1 (LAP2\u03b1)\/histone deacetylase 1 (HDAC1) complexes, thus inhibiting HDAC1\u2010mediated GLI1 deacetylation. Physalin B up\u2010regulated acetylation of GLI1, down\u2010regulated expression of GLI1 and subsequently inhibited HSC activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Physalin B exerted potent antifibrotic effects in vitro and in vivo by disrupting LAP2\u03b1\/HDAC1 complexes, increasing GLI1 acetylation and inactivating GLI1. This indicates that the phytochemical physalin B may be a potential therapeutic candidate for the treatment of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15490","type":"journal-article","created":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T09:33:33Z","timestamp":1618652013000},"page":"3428-3447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Physalin B attenuates liver fibrosis via suppressing LAP2\u03b1\u2013HDAC1\u2010mediated deacetylation of the transcription factor GLI1 and hepatic stellate cell activation"],"prefix":"10.1111","volume":"178","author":[{"given":"Xiaoyun","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy China Pharmaceutical University  Nanjing 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