{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:25:05Z","timestamp":1791404705241,"version":"4.3.3"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Guangdong Natural Science Foundation","doi-asserted-by":"crossref","award":["9351503102000001"],"award-info":[{"award-number":["9351503102000001"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"name":"J. K. de Cock Foundation"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits, has been reported to have anti\u2010inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti\u2010inflammatory properties of hesperetin both <jats:italic>in vitro<\/jats:italic> and in models of fulminant hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Apoptotic cell death and inflammation were induced in primary cultures of rat hepatocytes by bile acids and cytokine mixture respectively. Apoptosis was quantified by caspase\u20103 activity and necrosis by LDH release. The concanavalin A (ConA) and D\u2010galactosamine\/LPS (D\u2010GalN\/LPS) were used as models of fulminant hepatitis. Liver injury was assessed by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver histology and TUNEL assay and inflammation by inducible NOS (iNOS) expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Hesperetin blocked bile acid\u2010induced apoptosis and cytokine\u2010induced inflammation in rat hepatocytes. Moreover, hesperetin improved liver histology and protected against hepatocyte injury in ConA\u2010 and D\u2010GalN\/LPS\u2010induced fulminant hepatitis, as assessed by TUNEL assay and serum AST and ALT levels. Hesperetin also reduced expression of the inflammatory marker iNOS and the expression and serum levels of TNF\u03b1 and IFN\u2010\u03b3, the main mediators of cell toxicity in fulminant hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Hesperetin has anti\u2010inflammatory and cytoprotective actions in models of acute liver toxicity. Hesperetin therefore has therapeutic potential for the treatment of inflammatory liver diseases accompanied by extensive hepatocyte injury, such as fulminant hepatitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13645","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T04:34:37Z","timestamp":1476333277000},"page":"41-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["The protective effect of the natural compound hesperetin against fulminant hepatitis <i>in vivo<\/i> and <i>in vitro<\/i>"],"prefix":"10.1111","volume":"174","author":[{"given":"Xueting","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou China"},{"name":"Department of Gastroenterology and Hepatology University Medical Center Groningen, University of Groningen  Groningen The 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