{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:49Z","timestamp":1791312709812,"version":"4.3.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T00:00:00Z","timestamp":1639872000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>NAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb <jats:italic toggle=\"yes\">Erigeron breviscapus<\/jats:italic>, exhibits a wide range of pharmacological properties, including effects on metabolism. However, the anti\u2010NASH efficacy and mechanisms of breviscapine have not yet been characterized.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis <jats:italic toggle=\"yes\">in vivo<\/jats:italic> and <jats:italic toggle=\"yes\">in vitro<\/jats:italic> under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high\u2010fat diet, a high\u2010fat\/high\u2010cholesterol diet, or a methionine\u2010 and choline\u2010deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA\u2010sequencing and multiomics analyses further indicated that the key mechanism linking the anti\u2010NASH effects of breviscapine was inhibition of TGF\u2010\u03b2\u2010activated kinase 1 (TAK1) phosphorylation and the subsequent mitogen\u2010activated protein kinase signaling cascade. Treatment with the TAK1 inhibitor 5Z\u20107\u2010oxozeaenol abrogated breviscapine\u2010mediated hepatoprotection under metabolic stress. Molecular docking illustrated that breviscapine directly bound to TAK1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Breviscapine prevents metabolic stress\u2013induced NASH progression through direct inhibition of TAK1 signaling. Breviscapine might be a therapeutic candidate for the treatment of NASH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32221","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T14:42:29Z","timestamp":1635604949000},"page":"155-171","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":102,"title":["Breviscapine alleviates NASH by inhibiting TGF\u2010\u03b2\u2010activated kinase 1\u2010dependent signaling"],"prefix":"10.1097","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-6883","authenticated-orcid":false,"given":"Tian","family":"Lan","sequence":"first","affiliation":[{"name":"Institute of Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,China"},{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine,Guangzhou,China"},{"name":"Key Laboratory of Glucolipid Metabolic Disorder,Ministry of 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