3-O-Acetyloleanolic acid alleviates autoimmune liver injury by targeting FXR

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease mediated by autoimmune mechanisms. 3-O-Acetyloleanolic acid (OAA), a triterpenoid isolated from the stems of syringa oblata Lindl. has demonstrated therapeutic potential for liver and immune-related disorders. The farnesoid X receptor (FXR) plays a critical role in regulating bile acid metabolism within the enterohepatic circulation and modulates metabolic dysregulation and immune homeostasis across multiple tissues.

This study investigated the protective effect of OAA against concanavalin A (ConA)-induced liver injury and elucidated its underlying mechanisms.

OAA efficacy in ConA-induced AIH mice was assessed through serum ALT/AST levels, histopathological evaluation (H&E staining), and T lymphocyte profiling. OAA's mechanism was analyzed via integrated multi-omics, with action pathways validated by Western blot (WB) and immunofluorescence. Direct targets were confirmed through cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), cellular transfection, and FXR-knockdown murine models.

OAA significantly ameliorated ConA-induced liver injury in AIH mice. Multi-omics analysis revealed that OAA activates the primary bile acid synthesis pathway via FXR, attenuating hepatic metabolic dysregulation and injury. Critically, siRNA-mediated FXR knockdown in vitro, alongside studies in FXR-heterozygous (FXR^+/-) and wild-type mice, confirmed that OAA confers hepatoprotective effects by directly binding FXR protein.

OAA demonstrates significant potential as a therapeutic candidate for mitigating liver injury in AIH, primarily through direct targeting and activation of the FXR pathway.