{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:25:10Z","timestamp":1777868710327,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Drug\u2010induced liver injury (DILI) represents a critical pharmacotherapeutic challenge requiring novel interventions. The hepatoprotective mechanisms of Gypenoside XLIX (GYP XLIX) against liver injury remain underexplored. This study establishes GYP XLIX as a hepatoprotective agent against diclofenac (DF)\u2010induced liver injury through integrated experimental approaches. Male Wistar rats were used in this investigation and grouped randomly into four groups: the control group, the DF group (50\u2009mg\/kg), the GYP XLIX group (30\u2009mg\/kg), the DF\u2009+\u2009XLIX group, and the DF + silymarin group for 7 days. Human liver cell line L02 was used for further study. The analytical methods used included network pharmacology analysis, molecular docking, H&amp;E staining, qPCR, enzyme activity assay, and Western blot. GYP XLIX significantly ameliorated DF\u2010induced hepatic damage, as evidenced by reduced serum ALT, AST, and ALP levels, attenuated histopathological abnormalities, enhanced antioxidant capacity (elevated SOD and GSH, decreased MDA), and suppressed pro\u2010inflammatory cytokine release. Mechanistically, GYP XLIX targeted the AKT\/NLRP3 pathway, promoting AKT phosphorylation and inhibiting NLRP3 inflammasome activation, confirming its role in alleviating hepatotoxicity through antioxidative and anti\u2010inflammatory mechanisms. In L02 cells, GYP XLIX exerts a protective effect against DF\u2010induced liver injury through the AKT\/NLRP3 axis, and this mechanism has been further confirmed. This work supports GYP XLIX as a promising multi\u2010target therapeutic candidate for chemical hepatotoxicity, providing new insights for clinical prevention and treatment of DILI.<\/jats:p>","DOI":"10.1002\/jbt.70686","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T17:40:07Z","timestamp":1767807607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gypenoside XLIX Alleviates Diclofenac\u2010Induced Hepatotoxicity via Modulating Akt\/NLRP3 Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Mingkai","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Traumatology The 964th Hospital of PLA Joint Logistic Support Force Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daxin","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Traumatology The 964th Hospital of PLA Joint Logistic Support 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