{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:08:51Z","timestamp":1790352531027,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Non-alcoholic fatty liver disease (NAFLD) is a widespread disease, but no recognized drug treatment exists. Previous studies have shown that artemether (Art) can ameliorate carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2013induced liver fibrosis in mice. This study sets out to observe the therapeutic impact of Art on non-alcoholic steatohepatitis (NASH).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Model mice were provided with a methionine- and choline-deficient (MCD) diet for 4\u00a0weeks or a high-fat diet (HFD) for 28\u00a0weeks, respectively, and then treated with Art. RNA sequencing (RNA-Seq) analyzed gene expression changes caused by Art treatment. The molecular mechanism of the therapeutic effects of Art on NASH was studied in the mouse liver and HepG2 cells.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Art treatment significantly attenuated hepatic lipid accumulation and liver damage in MCD diet\u2013 or HFD-induced NASH mice. The RNA-Seq analysis revealed lipid metabolism as a major pathway suppressed by Art administration, in addition to the regulation of inflammation pathways. Mechanistically, Art reduced lipid accumulation by repressing <jats:italic>de novo<\/jats:italic> lipogenesis of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD1), promoting lipolysis of peroxisome proliferator\u2013activated receptor-\u03b3 co-activator-1\u03b1 (PGC1\u03b1), adipose triglyceride lipase (ATGL), and carnitine palmitoyltransferase I (CPT-1a) in NASH mouse liver and HepG2 cells. In addition, Art inhibited the secretion of pro-inflammatory factors and reduced inflammatory infiltration by effectively inhibiting M1 macrophage activation. Furthermore, Art inhibited transforming growth factor-beta 1 (TGF-\u03b2), and the SMAD signaling pathway mediates the development of liver fibrosis.<\/jats:p><jats:p><jats:bold>Inclusion<\/jats:bold>: Art improved fat deposition by repressing <jats:italic>de novo<\/jats:italic> lipogenesis and promoting lipolysis <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Furthermore, Art improved inflammation and fibrosis with a significant effect. It is a prospective therapeutic agent for NASH.<\/jats:p>","DOI":"10.3389\/fphar.2022.851342","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T05:21:16Z","timestamp":1651468876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Artemether Ameliorates Non-Alcoholic Steatohepatitis by Repressing Lipogenesis, Inflammation, and Fibrosis in Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Jia","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Asakiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunlun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1016\/j.cgh.2020.08.065","article-title":"A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma","volume":"19","author":"Chalasani","year":"2020","journal-title":"Clin. 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