Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 04 1 9 EN Jafar Salimian Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Soheil Vazifedust Solid Tumor Research Centre, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences,Urmia,Iran Majid Mirzaei Nodooshan Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Hadi Esmaeili Gouvarchin Ghaleh Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 10 06 2025 11 07 Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that can progress to cirrhosis and liver failure if untreated. Current therapies, mainly corticosteroids, are effective but limited by adverse effects and incomplete responses, prompting the search for safer alternatives. Peiminine, an alkaloid derived from Fritillaria species, has demonstrated anti-inflammatory and antioxidant properties in several disease models. This study evaluated its efficacy in a concanavalin A (ConA)–induced mouse model of AIH. Male C57BL/6 mice were divided into six groups, including ConA-injured animals, and treatment groups receiving peiminine (3 mg/kg, i.p.), prednisolone (10 mg/kg, i.p.), or their combination. ConA injection caused sharp increases in ALT (↑ 5.4-fold), AST (↑ 4.8-fold), and ALP (↑ 3.9-fold), alongside marked elevations in MPO activity, nitric oxide, and pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ). Peiminine significantly reversed these alterations—reducing ALT, AST, and ALP by 65% to 75% and restoring IL-4, TGF-β, and SOD activity toward normal values. Pre-treatment provided stronger protection than post-treatment, and outcomes were comparable to those of prednisolone, with combination therapy yielding the greatest improvement across all indices. These findings indicate that peiminine mitigates immune-mediated hepatic injury by modulating cytokines, reducing oxidative stress, and maintaining liver integrity. Peiminine may represent a promising preventive or adjunct therapy for AIH, warranting further mechanistic and long-term investigations. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4610 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4610/2290