{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:07:39Z","timestamp":1792148859256,"version":"4.4.0"},"reference-count":70,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"National Council of Science and Technology (Conacyt) of Mexico","doi-asserted-by":"publisher","award":["53358"],"award-info":[{"award-number":["53358"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"National Council of Science and Technology (Conacyt) of Mexico","doi-asserted-by":"publisher","award":["A1-S-27705"],"award-info":[{"award-number":["A1-S-27705"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"National Council of Science and Technology (Conacyt) of Mexico","doi-asserted-by":"publisher","award":["724340"],"award-info":[{"award-number":["724340"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg\/kg, i.p.) of CCl4. Caffeine was administered at 50 mg\/kg p.o. The effects of HFSCD+CCl4 and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl4-treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-\u03baB (NF-\u03baB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4\/MAPK\/NF-\u03baB signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms23179954","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T21:27:17Z","timestamp":1662067637000},"page":"9954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4\/MAPK\/NF-\u03baB Signaling Pathway in an Experimental NASH Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9601-5893","authenticated-orcid":false,"given":"Eduardo E.","family":"Vargas-Pozada","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-9760","authenticated-orcid":false,"given":"Erika","family":"Ramos-Tovar","sequence":"additional","affiliation":[{"name":"Postgraduate Studies and Research Section, School of Higher Education in Medicine-IPN, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tom\u00e1s, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan D.","family":"Rodriguez-Callejas","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroplasticity and Neurodegeneration, Department of Pharmacology, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-6354","authenticated-orcid":false,"given":"Irina","family":"Cardoso-Lezama","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Galindo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0982-2241","authenticated-orcid":false,"given":"Daniel","family":"Talam\u00e1s-Lara","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-8235","authenticated-orcid":false,"given":"Ver\u00f3nica Roc\u00edo","family":"V\u00e1squez-Garz\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratory of Fibrosis and Cancer, Faculty of Medicine and Surgery, \u2018Benito Ju\u00e1rez\u2019 Autonomous University of Oaxaca, UABJO, Oaxaca 68020, Mexico"},{"name":"Directorate of Catedras, National Council of Science and Technology CONACYT, Mexico City 03940, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-4870","authenticated-orcid":false,"given":"Jaime","family":"Arellanes-Robledo","sequence":"additional","affiliation":[{"name":"Directorate of Catedras, National Council of Science and Technology CONACYT, Mexico City 03940, Mexico"},{"name":"Laboratory of Liver Diseases, National Institute of Genomic Medicine, INMEGEN, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Infectomics and Molecular Pathogenesis, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00fal","family":"Villa-Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2236-6631","authenticated-orcid":false,"given":"Pablo","family":"Muriel","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","unstructured":"Muriel, P. 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