Abstract
Background Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disease caused by impaired insulin secretion or insulin resistance, which induces glucose, fat, and protein metabolism disorders in the body
We studied the role of clusters 1, 2, and 3 in gene function and obtained 123, 137, and 119 Gene Ontology (GO) entries, respectively, which were primarily involved in cell response to different stimuli, inflammatory response, regulation of apoptotic process, and IL-2 IL-6
Further molecular docking assay in this study showed that quercetin was verified strong binding activity with AKT1, IL-6, and FOS, while baicalein had strong combination with AKT1 and FOS, wogonin had strong combination with AKT1 and IL-6, kaempferol had strong combination with AKT1, and oroxylin A had strong combination with IL-6
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disease caused by impaired insulin secretion or insulin resistance, which induces glucose, fat, and protein metabolism disorders in the body. Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines This decoction has long been used in China for clinically treating T2DM. This study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. Expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A.
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