Abstract
BackgroundThe traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods.MethodsFirstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed.Results68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway.ConclusionsThis study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.
Highlights
The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis
Various pathological factors, such as hepatitis B and C viruses (HBV and Hepatitis C virus (HCV)), Wang et al Chin Med (2021) 16:59 alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) especially non-alcoholic steatohepatitis (NASH), primary biliary cholangitis, primary sclerosing cholangitis, and other autoimmune liver diseases, all contribute to the development of liver fibrosis [1]
Matrix metalloproteinase-9 (MMP9), Hypoxia-inducible factor-1α (HIF1A) and SERPINE1, three targets that in the critical compound-liver fibrosis target (CLFT) bipartite network, in addition to Matrix metalloproteinase-2 (MMP2), a target not appeared in the critical CLFT network but in the global CLFT network, which were correlated with fibrogenesis and degradation
Summary
The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. Liver fibrosis is a pathological condition that occurs as a response to chronic liver injury. Various pathological factors, such as hepatitis B and C viruses (HBV and HCV), Wang et al Chin Med (2021) 16:59 alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) especially non-alcoholic steatohepatitis (NASH), primary biliary cholangitis, primary sclerosing cholangitis, and other autoimmune liver diseases, all contribute to the development of liver fibrosis [1]. In the context of chronic liver injury, hepatic stellate cells (HSCs) are over-activated, which triggers the excessive deposition of extracellular matrix (ECM) proteins and tissue structural remodelling [3]. Currently there is no validated anti-fibrogenic therapy yet [4,5,6,7]
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