Multiomics combined analysis reveals protective effect of 7-O-α-L-rhamnopyranosyl-kaempferol-3-O-β-D-glucopyranoside on autoimmune hepatitis.

Background: Autoimmune hepatitis (AIH) seriously endangers human health. Therefore, it is urgent to find new therapeutic drugs and targets for AIH. In this context, 7-O-α-L-rhamnopyranosyl-kaempferol-3-O-β-D-glucopyranoside (KGR), a flavonoid compound found in Embelia laeta (L.) Mez, has not been evaluated for its efficacy.

Objective: This study aimed to investigate the therapeutic effect and mechanisms of KGR on AIH.

Research Design: Concanavalin A (Con A) was used to establish a mouse AIH model. Molecular biology methods were used to evaluate the efficacy of KGR and transcriptomics, proteomics, and metabolomics were innovatively combined to revel the mechanism of action of KGR against AIH, which was verified by experiments.

Results: Mouse liver sections demonstrated that KGR reduced the degree of degeneration and necrosis in liver cells in mice. Compared with the Con A group, KGR significantly reduced serum aminotransferase levels, inhibited the release of proinflammatory cytokines in the liver tissue, and inhibited oxidative stress (OS) by reducing malondialdehyde level and enhancing superoxide dismutase activity. Finally, multiomics revealed that primary bile acids synthesis and the FXR-TLR4/MYD88/JNK signaling pathway may be the regulatory targets of KGR.

Conclusion: The study results demonstrated that KGR inhibited OS and inflammatory responses by regulating primary bile acid synthesis and thereby inhibiting the FXR-TLR4/MYD88/JNK signaling pathway, and had a protective effect on Con A-induced AIH.