{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:58:37Z","timestamp":1787497117548,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Key laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","award":["SIMM2103ZZ-04"],"award-info":[{"award-number":["SIMM2103ZZ-04"]}]},{"name":"State Key laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","award":["P2022-KF06"],"award-info":[{"award-number":["P2022-KF06"]}]},{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China","award":["SIMM2103ZZ-04"],"award-info":[{"award-number":["SIMM2103ZZ-04"]}]},{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China","award":["P2022-KF06"],"award-info":[{"award-number":["P2022-KF06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease worldwide, with no effective therapies available. Discovering lead compounds from herb medicine might be a valuable strategy for the treatment of NASH. Here, we discovered Alisol B, a natural compound isolated from Alisma orientalis (Sam.), that attenuated hepatic steatosis, inflammation, and fibrosis in high-fat diet plus carbon tetrachloride (DIO+CCl4)-induced and choline-deficient and amino acid-defined (CDA)-diet-induced NASH mice. RNA-seq showed Alisol B significantly suppressed CD36 expression and regulated retinol metabolism in NASH mice. In mouse primary hepatocytes, Alisol B decreased palmitate-induced lipid accumulation and lipotoxicity, which were dependent on CD36 suppression. Further study revealed that Alisol B enhanced the gene expression of RAR\u03b1 with no direct RAR\u03b1 agonistic activity. The upregulation of RAR\u03b1 by Alisol B reduced HNF4\u03b1 and PPAR\u03b3 expression and further decreased CD36 expression. This effect was fully abrogated after RAR\u03b1 knockdown, suggesting Alisol B suppressed CD36 via regulating RAR\u03b1-HNF4\u03b1-PPAR\u03b3 cascade. Moreover, the hepatic gene expression of RAR\u03b1 was obviously decreased in murine NASH models, whereas Alisol B significantly increased RAR\u03b1 expression and decreased CD36 expression, along with the downregulation of HNF4\u03b1 and PPAR\u03b3. Therefore, this study showed the unrecognized therapeutic effects of Alisol B against NASH with a novel mechanism by regulating RAR\u03b1-PPAR\u03b3-CD36 cascade and highlighted Alisol B as a promising lead compound for the treatment of NASH.<\/jats:p>","DOI":"10.3390\/nu14122411","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"2411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Alisol B Alleviates Hepatocyte Lipid Accumulation and Lipotoxicity via Regulating RAR\u03b1-PPAR\u03b3-CD36 Cascade and Attenuates Non-Alcoholic Steatohepatitis in Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhuohui","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Tao","family":"Deng","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suling","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Ning","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin-Shi","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Leng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. 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