{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:03:44Z","timestamp":1785229424841,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Xenobiot.","JoX"],"abstract":"<jats:p>Background: Autoimmune hepatitis (AIH) represents a clinically challenging immune-mediated liver disease, owing to its complex pathogenesis and limited targeted therapeutic options. Growing evidence highlights the key role of lymphocyte-mediated hepatic inflammation, dysregulated cytokine milieu, and oxidative stress in AIH progression. Oridonin (ORI), a bioactive diterpenoid with well-established antioxidant, anti-inflammatory, and immunoregulatory effects, remains unexplored in AIH. The present work aims to survey the potential impacts of ORI in Concanavalin A (Con A)-prompted AIH in mice, with particular emphasis on TLR7\/PKM2\/NLRP3 inflammatory signaling and macrophage polarization. Methods: Male BALB\/c mice (n = 30) were allocated into five groups: CTR group, ORI-CTR group, Con A group, ORI (5 mg\/kg) + Con A group, and ORI (10 mg\/kg) + Con A group. ORI was administered i.p. for 4 days before a single Con A injection (15 mg\/kg i.v.). Serum liver enzymes, hepatic pathological changes, oxidative milieu, and varied immunological factors were assessed. Results: ORI markedly attenuated Con A-induced hepatic injury, as evidenced by the reduced liver transaminases, preserved hepatic architecture, and restored oxidative milieu. Moreover, ORI suppressed T-cell activation, modulated M1\/M2 polarization, and reduced pro-inflammatory cytokines. These effects were accompanied by the suppression of TLR7\/PKM2\/NLRP3 inflammatory signaling. Conclusions: ORI exhibits hepatoprotective effects against Con A-induced AIH and these effects are associated with the modulation of inflammatory and immunometabolic responses as well as downregulating TLR7\/PKM2\/NLRP3 signaling.<\/jats:p>","DOI":"10.3390\/jox16040138","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oridonin Ameliorates Concanavalin A-Elicited Hepatitis in Mice: Insight into Suppressing TLR7\/PKM2\/NLRP3-Driven Inflammation and M1\/M2 Polarization"],"prefix":"10.3390","volume":"16","author":[{"given":"Saif","family":"Dhahir","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma M.","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8590-2622","authenticated-orcid":false,"given":"Manar A.","family":"Nader","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura National University, Gamasa 7731168, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0458","DOI":"10.1097\/HC9.0000000000000458","article-title":"Autoimmune hepatitis: Current and future therapies","volume":"8","author":"Reau","year":"2024","journal-title":"Hepatol. 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