{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:18:48Z","timestamp":1784045928548,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012544","name":"China Medical University, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012544","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that causes severe liver damage, fibrosis, and scarring. Despite its potential to progress to cirrhosis or hepatic failure, approved drugs or treatments are currently unavailable. We developed 4,4\u2010diallyl curcumin bis(2,2\u2010hydroxymethyl)propanoate, also known as <jats:bold>35e<\/jats:bold>, which induces upregulation of mitochondrial proteins including carnitine palmitoyltransferase I (CPT\u2010I), carnitine palmitoyltransferase II, heat shock protein 60, and <jats:italic>translocase<\/jats:italic> of the <jats:italic>outer<\/jats:italic> mitochondrial <jats:italic>membrane 20<\/jats:italic>. Among these proteins, the upregulated expression of CPT\u2010I was most prominent. CPT\u2010I plays a crucial role in transporting carnitine across the mitochondrial inner membrane, thereby initiating mitochondrial \u03b2\u2010oxidation of fatty acids. Given recent research showing that CPT\u2010I activation could be a viable pathway for NASH treatment, we hypothesized that <jats:bold>35e<\/jats:bold> could serve as a potential agent for treating NASH. The efficacy of <jats:bold>35e<\/jats:bold> in treating NASH was evaluated in methionine\u2010 and choline\u2010deficient (MCD) diet\u2010 and Western diet <jats:italic>(<\/jats:italic>WD)\u2010induced models that mimic human NASH. In the MCD diet\u2010induced model, both short\u2010term (2\u2009weeks) and long\u2010term (7\u2009weeks) treatment with <jats:bold>35e<\/jats:bold> effectively regulated elevated serum alanine aminotransferase (ALT)\/aspartate aminotransferase (AST) concentrations and histological inflammation. However, the antisteatotic effect of <jats:bold>35e<\/jats:bold> was obtained only in the short\u2010term treatment group. As a comparative compound in the MCD diet\u2010induced model, curcumin treatment did not produce significant regulatory effects on the liver triglyceride\/total cholesterol, serum ALT\/AST, or hepatic steatosis. In the WD\u2010induced model, <jats:bold>35e<\/jats:bold> ameliorated hepatic steatosis and hepatic inflammation, while increasing serum AST and hepatic lipid content. A decrease in epididymal adipose tissue weight and serum free fatty acid concentration suggested that <jats:bold>35e<\/jats:bold> may promote lipid metabolism or impede lipid accumulation. Overall, <jats:bold>35e<\/jats:bold> displayed significant antilipid accumulation and antifibrotic effects in the two complementary mice models. The development of new curcumin derivatives with the ability to induce CPT\u2010I upregulation could further underscore their efficacy as anti\u2010NASH agents.<\/jats:p>","DOI":"10.1111\/cbdd.14532","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T03:29:41Z","timestamp":1715311781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["4,<scp>4\u2010Diallyl<\/scp> curcumin bis(2,2\u2010hydroxymethyl)propanoate ameliorates nonalcoholic steatohepatitis in methionine\u2010choline\u2010deficient diet and Western diet mouse models"],"prefix":"10.1111","volume":"103","author":[{"given":"Li\u2010Chan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Post\u2010Baccalaureate Medicine College of Medicine, National Chung Hsing University  Taichung 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