{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:22Z","timestamp":1787029102759,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Developing Scheme of Jilin Province of People\u2019s Republic of China","award":["20210101032JC"],"award-info":[{"award-number":["20210101032JC"]}]},{"name":"Scientific and Technological Developing Scheme of Jilin Province of People\u2019s Republic of China","award":["20230101189JC"],"award-info":[{"award-number":["20230101189JC"]}]},{"name":"Scientific and Technological Developing Scheme of Jilin Province of People\u2019s Republic of China","award":["82304848"],"award-info":[{"award-number":["82304848"]}]},{"name":"Scientific and Technological Developing Scheme of Jilin Province of People\u2019s Republic of China","award":["20200104086"],"award-info":[{"award-number":["20200104086"]}]},{"name":"National Natural Science Foundation of China","award":["20210101032JC"],"award-info":[{"award-number":["20210101032JC"]}]},{"name":"National Natural Science Foundation of China","award":["20230101189JC"],"award-info":[{"award-number":["20230101189JC"]}]},{"name":"National Natural Science Foundation of China","award":["82304848"],"award-info":[{"award-number":["82304848"]}]},{"name":"National Natural Science Foundation of China","award":["20200104086"],"award-info":[{"award-number":["20200104086"]}]},{"name":"Jilin City Science and Technology Innovation Development Plan Project","award":["20210101032JC"],"award-info":[{"award-number":["20210101032JC"]}]},{"name":"Jilin City Science and Technology Innovation Development Plan Project","award":["20230101189JC"],"award-info":[{"award-number":["20230101189JC"]}]},{"name":"Jilin City Science and Technology Innovation Development Plan Project","award":["82304848"],"award-info":[{"award-number":["82304848"]}]},{"name":"Jilin City Science and Technology Innovation Development Plan Project","award":["20200104086"],"award-info":[{"award-number":["20200104086"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alcoholic liver disease (ALD) is the main factor that induces liver-related death worldwide and represents a common chronic hepatopathy resulting from binge or chronic alcohol consumption. This work focused on revealing the role and molecular mechanism of nodakenin (NK) in ALD associated with hepatic inflammation and lipid metabolism through the regulation of Nur77-P2X7r signaling. In this study, an ALD model was constructed through chronic feeding of Lieber\u2013DeCarli control solution with or without NK treatment. Ethanol (EtOH) or NK was administered to AML-12 cells, after which Nur77 was silenced. HepG2 cells were exposed to ethanol (EtOH) and subsequently treated with recombinant Nur77 (rNur77). Mouse peritoneal macrophages (MPMs) were treated with lipopolysaccharide\/adenosine triphosphate (LPS\/ATP) and NK, resulting in the generation of conditioned media. In vivo, histopathological alterations were markedly alleviated by NK, accompanied by reductions in serum triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and the modulation of Lipin-1, SREBP1, and Nur77 levels in comparison to the EtOH-exposed group (p &lt; 0.001). Additionally, NK reduced the production of P2X7r and NLRP3. NK markedly upregulated Nur77, inhibited P2X7r and Lipin-1, and promoted the function of Cytosporone B, a Nur77 agonist (p &lt; 0.001). Moreover, Nur77 deficiency weakened the regulatory effect of NK on P2X7r and Lipin-1 inhibition (p &lt; 0.001). In NK-exposed MPMs, cleaved caspase-1 and mature IL-1\u03b2 expression decreased following LPS\/ATP treatment (p &lt; 0.001). NK also decreased inflammatory-factor production in primary hepatocytes stimulated with MPM supernatant. NK ameliorated ETOH-induced ALD through a reduction in inflammation and lipogenesis factors, which was likely related to Nur77 activation. Hence, NK is a potential therapeutic approach to ALD.<\/jats:p>","DOI":"10.3390\/molecules29051078","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T05:59:19Z","timestamp":1709186359000},"page":"1078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Regulation of the Nur77-P2X7r Signaling Pathway by Nodakenin: A Potential Protective Function against Alcoholic Liver Disease"],"prefix":"10.3390","volume":"29","author":[{"given":"Jian","family":"Song","sequence":"first","affiliation":[{"name":"College of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Feng","family":"Qin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Yuan","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Yun","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Science, Traditional Chinese Medicine Biotechnology Innovation Center in Jilin Province, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Ming","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Beihua University, Jilin 132013, China"},{"name":"College of Science, Traditional Chinese Medicine Biotechnology Innovation Center in Jilin Province, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/jgh.16282","article-title":"Alcohol and the mechanisms of liver disease","volume":"38","author":"Chen","year":"2023","journal-title":"J. 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