{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:08:44Z","timestamp":1790352524856,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100016022","name":"Data Center of Management Science, National Natural Science Foundation of China - Peking University","doi-asserted-by":"publisher","award":["82000555"],"award-info":[{"award-number":["82000555"]}],"id":[{"id":"10.13039\/501100016022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Non\u2010alcoholic steatohepatitis (NASH) has no effective treatment drug. Our previous study initially found that artemether (Art) treatment significantly attenuates NSAH by regulating liver lipid metabolism. This study further elucidates new mechanisms of Art in improving liver inflammation and provides evidence for drug repurposing. Herein, we utilized HFHF diet\u2010induced animal model and macrophage models to detect the mechanisms of Art in NASH. We confirmed that Art significantly reduced hepatic steatosis, injury, and fibrosis in a high\u2010fat high\u2010fructose (HFHF) diet\u2010induced animal model. Art significantly suppressed the activation of inflammatory macrophages and secretion of pro\u2010inflammatory cytokine (IL\u20101\u03b2) by reducing serum double\u2010stranded DNA (dsDNA) levels and triggering the AIM2\/Caspase\u20101\/GSDMD signaling in\u00a0vivo. dsDNA\u2010induced Caspase\u20101 and PI\u2010positive cells pyroptosis, AIM2 inflammasome activation, IL\u20101\u03b2, and IL\u201018 secretion increase were inhibited by Art in\u00a0vitro. Furthermore, we found Art effectively suppressed mitochondrial DNA (mtDNA), a typical form of dsDNA, released from free fatty acid (FFA)\u2010stressed hepatocytes, which further inhibited AIM2 inflammasome mediated\u2010pyroptosis through decreasing the cleavage of Caspase\u20101\/GSDMD\/IL\u20101\u03b2. Moreover, inhibition of the\n                    <jats:italic>AIM2<\/jats:italic>\n                    gene partly reversed the inhibitory effect of Art on macrophage pyroptosis. Impaired mitochondrial structure and function were confirmed in FFA\u2010stressed hepatocytes and the HFHF\u2010diet\u2010induced NASH mouse model, which was reversed by Art treatment. The present study provides evidence for Art as a potential anti\u2010pyroptosis therapeutic agent for NASH treatment.\n                  <\/jats:p>","DOI":"10.1002\/ptr.8393","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T22:19:53Z","timestamp":1732832393000},"page":"604-618","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Artemether Ameliorates Non\u2010Alcoholic Steatohepatitis by Restraining Cross\u2010Talk Between Lipotoxicity\u2010Induced Hepatic Hepatocytes and Macrophages"],"prefix":"10.1002","volume":"39","author":[{"given":"Jia","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering China Agricultural University  Beijing 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Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxin","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing Ditan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Yin","sequence":"additional","affiliation":[{"name":"Center of Liver Diseases, Beijing Ditan Hospital Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital Capital Medical University  Beijing 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