Studies on the Anti-HBV Mechanism of Syringopicroside Based on Serum Metabolomics

Aims: Syringopicroside (SYR) is an iridoid monomer compound isolated from the leaves of clove. HBV is a hepatotropic virus that can cause severe liver diseases, including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Syringopicroside has a significant effect on anti-HBV, but its mechanism of action is still unclear. Methods: A metabolomics approach based on UPLC-G2-Si-HDMS was performed to analyze the serum biomarkers from HBV transgenic mice to find the biomarkers affected by syringopicroside. Through the analysis of metabolic pathways, the key pathways of syringopicroside involved in a therapeutic action were explored to study its potential mechanism. Using network pharmacology, the "component-target-pathway" network of syringopicroside in the treatment of hepatitis B was constructed and combined with the results of metabolomics. Furthermore, the mechanism of action of syringopicroside against HBV was also discussed. Results: Serum metabolomics identified a total of 42 HBV-related biomarkers, of which 8 returned to normal levels after syringopicroside treatment, involving a total of 6 metabolic pathways. Five biomarkers returned to normal levels after lamivudine treatment, involving 2 metabolic pathways. Network pharmacology analysis showed that syringopicroside in the treatment of hepatitis B mainly acts on 26 targets, including MMP9, MAPK1, and SLC29A1, involving 4 pathways. Conclusion: This study elucidates the multi-target and multi-channel integration mechanism of syringopicroside against HBV, lays a foundation for an in-depth study of the anti-HBV mechanism of syringopicroside, and also provides support for the development of innovative traditional Chinese medicines for the treatment of hepatitis B.