Piceatannol improves autoimmune hepatitis by inhibiting the immune activities of T cells and macrophages through binding with c-Jun.

Abstract

Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A mouse model of AIH was established by injecting ConA (i.v.), and PIC was administered as an intervention. The protective effect of PIC was evaluated by the liver function, liver pathology, and serum levels of inflammatory factors. Subsequently, network pharmacology was used to predict the pathways and targets of PIC in the treatment of AIH, and the predicted results were validated using flow cytometry, molecular docking, surface plasmon resonance (SPR) and so on. Finally, the immunosuppressive effect of PIC was further validated in a mouse heart transplantation model. PIC can improve liver function decline and reduce pathological liver damage, as well as inhibit the increase of serum inflammatory factor levels in mice with AIH induced by ConA. The protective effect is achieved by suppressing the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts and inhibit acute rejection reactions. These results indicated that PIC can significantly improve ConA-induced AIH in mice by inhibiting the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts in mice and inhibit acute rejection responses. The above results indicated that PIC may serve as a promising immunosuppressant and be effective for AIH.