Mechanistic study on HuaganJiedu decoction in treating hepatitis B based on multi-omics analysis of network pharmacology, metabolomics, and transcriptomics.

BACKGROUND

Traditional Chinese medicine (TCM), with its extensive historical background, provides herbal remedies such as HuaganJiedu Decoction (HGJDD) that may serve as adjuncts to conventional strategies for hepatitis B virus (HBV). HGJDD has been demonstrated effectiveness in enhancing clinical outcomes for patients with HBV.

PURPOSE: Uncovering the mechanism by which HGJDD acts in HBV treatment by Multi-omics analysis of Network Pharmacology, Metabolomics, and Transcriptomics.

METHOD: In this research, the composition of HGJDD was identified by LC-MS. Evaluate the effects of HGJDD through metabolomics analysis. We conducted in vitro and in vivo studies using HepG2.2.15 cells and HBV-TG mice, and detected HBsAg, HBeAg, and HBV DNA in different levels. Multi-omics analyses were used to identify the key mechanism influenced by HGJDD treatment. Molecular docking evaluated the components' interaction with the FXR/RXRα-SHP1-HNF1α axis. Immunohistochemistry, co-immunoprecipitation, and Western blotting verified the mechanisms underlying the action of HGJDD.

RESULT: Using LC-MS, the study identified compounds within HGJDD. HGJDD exhibited the ability to lower HBsAg, HBeAg, and HBV DNA in a dose- and duration-dependent manner. Multi-omics analyses identified that FXR/RXRα-SHP1-HNF1α axis is the potential therapeutic target for its therapeutic effect. Meanwhile, multiple components in HGJDD have good interactions with the proteins on this axis. Immunofluorescence, co-immunoprecipitation, and Western blotting demonstrated the influence of FXR/RXRα-SHP1-HNF1α axis.

CONCLUSION

FXR/RXRα-SHP1-HNF1α axis is main mechanism for HGJDD against HBV.