Peiminine modulates T cell-associated gene expression and inflammatory activity in experimental autoimmune hepatitis

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by immune-mediated hepatocellular injury and insufficient regulatory T cell (Treg) control. Despite the efficacy of corticosteroids and azathioprine, incomplete response, side effects, and relapse often limit treatment, underscoring the need for novel therapeutic strategies. To date, little is known about the potential of natural compounds in modulating T cell-related pathways in AIH. This study aimed to evaluate the therapeutic effects of peiminine, an alkaloid with reported anti-inflammatory and immunomodulatory properties, in an experimental model of AIH. We investigated its impact on liver histopathology, inflammatory markers, and expression of T cell-associated genes (FOXP3, Tbx21, and RORc), comparing its efficacy with prednisolone. Our results demonstrated that peiminine treatment significantly alleviated interface hepatitis, reduced inflammatory cell infiltration, and improved lobular architecture. Quantitative histological scoring confirmed that peiminine, particularly at higher doses, exerted protective effects comparable to prednisolone. At the molecular level, peiminine increased FOXP3 expression while suppressing Tbx21 and RORc, suggesting restoration of Treg/Th1/Th17 balance. These findings were consistent with reductions in pro-inflammatory cytokine expression and improved liver function indices. Collectively, our findings provide promising preclinical evidence that peiminine can attenuate autoimmune-mediated liver injury by modulating T cell-associated immune pathways. While further validation in human studies is necessary, these results identify peiminine as a potential adjunct or alternative therapeutic candidate for AIH, with implications for broader autoimmune disease management.