{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:42:56Z","timestamp":1792676576206,"version":"4.5.0"},"reference-count":66,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute hepatic injury (AHI) is a sudden onset of hepatic inflammation, a key contributor to the progression of diabetes and other disorders. Diabetes mellitus also increases the risk of liver illnesses associated with inflammatory disorders. According to recent studies, Saroglitazar (SAR), originally developed for the treatment of hyperglycemia and dyslipidemia, has also demonstrated notable anti\u2010inflammatory properties. In our search for a prime therapeutic approach for inflammatory liver disorders in diabetic patients, we investigated the effects of SAR on thioacetamide (TAA)\u2010induced AHI in rats. In order to investigate possible interactions between SAR and thioredoxin\u2010interacting protein (TXNIP), this research utilized a multistep methodology that included prediction of computational targets, network analysis, molecular docking, and experimental verification. Findings revealed the anti\u2010inflammatory potential of SAR, presumably ascribed to its inhibition of the NLRP3 signaling pathway by inhibiting TXNIP, an NLRP3 inflammasome upstream regulator. Furthermore, SAR inhibited the priming signal brought on by NF\u03baB stimulation and the succeeding inflammasome components, cleaved caspase\u20101, GSDMD, IL\u20101\u03b2, and IL\u201018. As a result, SAR demonstrated anti\u2010pyroptotic properties in the injured liver. Moreover, SAR exhibited potential antiapoptotic effects, as indicated by decreased Bax levels, decreased tissue expression of cleaved caspase\u20103, and increased BCL2 levels. Improvements in liver function, oxidative stress markers, liver histology, and the liver weight\u2010to\u2010body weight ratio all supported these findings. In conclusion, SAR demonstrates potential as a preventive treatment for inflammatory liver disorders. To render these preclinical findings into efficient techniques for enhancing hepatic function, more research is required, particularly in the context of diabetes.<\/jats:p>","DOI":"10.1002\/ardp.70179","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:01:56Z","timestamp":1766988116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting TXNIP With Saroglitazar Mitigates Acute Hepatic Injury in Rats Challenged With Thioacetamide: A Multistep Computational and Experimental Approach"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6040-0575","authenticated-orcid":false,"given":"Fatma","family":"Elnaghy","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura National University Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-7851","authenticated-orcid":false,"given":"Sameh","family":"Saber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Abd El\u2010Kader","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Elmorsy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Mansoura University Mansoura Egypt"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Delta University for Science and Technology Gamasa Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S. 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