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Mechanistic study on HuaganJiedu decoction in treating hepatitis B based on multi-omics analysis of network
Hongxuan Tong1, Jiale Zhang1, Lijie Jiang1
1Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
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.
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