Protective Effect of Mesaconate on Autoimmune Hepatitis via Suppression of Inflammatory Response and Oxidative Stress

作者：Qian Zhang, Jiajun Wang, Yifan He, Kun Zhang, Hong Wei, Tao Han · 发表于：Journal of Clinical and Translational Hepatology · 年份：2025 · DOI：10.14218/jcth.2025.00112 · 被引用次数：2 · 研究领域：Liver Diseases and Immunity、Liver physiology and pathology、Liver Disease Diagnosis and Treatment

Background and Aims: Autoimmune hepatitis (AIH) is a severe immune-mediated liver disease with limited treatment options beyond immunosuppressants, which carry significant side effects. Existing evidence suggests that mesaconate (MSA) possesses immunomodulatory properties and may offer advantages over itaconate derivatives by avoiding succinate dehydrogenase inhibition. However, its specific role in AIH remains unclear. This study aimed to investigate the therapeutic effects of MSA on AIH and to elucidate its underlying mechanisms of action. Methods: validation was conducted using RAW264.7 macrophages pretreated with MSA (1 mM) followed by interferon-gamma (IFN-γ, 50 ng/mL) stimulation. Results: . The underlying protective mechanism involved MSA-mediated downregulation of IFN-γ expression and subsequent inhibition of the Janus tyrosine kinase 1/2-signal transducer and activator of transcription 1 signaling pathway. The involvement of this pathway in human AIH was also confirmed. Conclusions: This study provides the first evidence that MSA ameliorates AIH by suppressing the IFN-γ-Janus tyrosine kinase 1/2-signal transducer and activator of transcription 1 signaling pathway, offering novel mechanistic insights and a promising therapeutic candidate for the future treatment of autoimmune disorders.