{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:11:04Z","timestamp":1788401464817,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T00:00:00Z","timestamp":1586304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005496","name":"American Foundation for Pharmaceutical Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005496","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009412","name":"School of Pharmacy, University of Southern California","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Excess alcohol (ethanol, EtOH) consumption is a significant cause of chronic liver disease, accounting for nearly half of the cirrhosis\u2010associated deaths in the United States. EtOH\u2010induced liver toxicity is linked to EtOH metabolism and its associated increase in proinflammatory cytokines, oxidative stress, and the subsequent activation of Kupffer cells. Dihydromyricetin (DHM), a bioflavonoid isolated from <jats:italic>Hovenia dulcis<\/jats:italic>, can reduce EtOH intoxication and potentially protect against chemical\u2010induced liver injuries. But there remains a paucity of information regarding the effects of DHM on EtOH metabolism and liver protection. As such, the current study tests the hypothesis that DHM supplementation enhances EtOH metabolism and reduces EtOH\u2010mediated lipid dysregulation, thus promoting hepatocellular health.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The hepatoprotective effect of DHM (5 and 10\u00a0mg\/kg; intraperitoneal injection) was evaluated using male C57BL\/6J mice and a forced drinking ad libitum EtOH feeding model and HepG2\/VL\u201017A hepatoblastoma cell models. EtOH\u2010mediated lipid accumulation and DHM effects against lipid deposits were determined via H&amp;E stains, triglyceride measurements, and intracellular lipid dyes. Protein expression of phosphorylated\/total proteins and serum and hepatic cytokines was determined via Western blot and protein array. Total NAD<jats:sup>+<\/jats:sup>\/NADH Assay of liver homogenates was used to detect NAD\u00a0+\u00a0levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DHM reduced liver steatosis, liver triglycerides, and liver injury markers in mice chronically fed EtOH. DHM treatment resulted in increased activation of AMPK and downstream targets, carnitine palmitoyltransferase (CPT)\u20101a, and acetyl CoA carboxylase (ACC)\u20101. DHM induced expression of EtOH\u2010metabolizing enzymes and reduced EtOH and acetaldehyde concentrations, effects that may be partly explained by changes in NAD<jats:sup>+<\/jats:sup>. Furthermore, DHM reduced the expression of proinflammatory cytokines and chemokines in sera and cell models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In total, these findings support the utility of DHM as a dietary supplement to reduce EtOH\u2010induced liver injury via changes in lipid metabolism, enhancement of EtOH metabolism, and suppressing inflammation responses to promote liver health.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14326","type":"journal-article","created":{"date-parts":[[2020,4,8]],"date-time":"2020-04-08T13:37:06Z","timestamp":1586353026000},"page":"1046-1060","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Dihydromyricetin Protects the Liver via Changes in Lipid Metabolism and Enhanced Ethanol 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