Abstract
Background Huangqi Guizhi Wuwu Decoction (HGWD) has been applied in the treatment of joint pain for more than 1000 years in China. Currently, most physicians use HGWD to treat rheumatoid arthritis (RA), and it has proved to have high efficacy. Therefore, it is necessary to explore the potential mechanism of action of HGWD in RA treatment based on network pharmacology and molecular docking methods. Methods The active compounds of HGWD were collected, and their targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and DrugBank database, respectively. The RA-related targets were retrieved by analyzing the differentially expressed genes between RA patients and healthy individuals. Subsequently, the compound-target network of HGWD was constructed and visualized through Cytoscape 3.8.0 software. Protein-protein interaction (PPI) network was constructed to explore the potential mechanisms of HGWD on RA using the plugin BisoGenet of Cytoscape 3.8.0 software. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software (Bioconductor, clusterProfiler). Afterward, molecular docking was used to analyze the binding force of the top 10 active compounds with target proteins of VCAM1, CTNNB1, and JUN. Results Cumulatively, 790 active compounds and 1006 targets of HGWD were identified. A total of 4570 differentially expressed genes of RA with a p value <0.05 and |log 2(fold change)| > 0.5 were collected. Moreover, 739 GO entries of HGWD on RA were identified, and 79 pathways were screened based on GO and KEGG analysis. The core target gene of HGWD in RA treatment was JUN. Other key target genes included FOS, CCND1, IL6, E2F2, and ICAM1. It was confirmed that the TNF signaling pathway and IL-17 signaling pathway are important pathways of HGWD in the treatment of RA. The molecular docking results revealed that the top 10 active compounds of HGWD had a strong binding to the target proteins of VCAM1, CTNNB1, and JUN. Conclusion HGWD has important active compounds such as quercetin, kaempferol, and beta-sitosterol, which exert its therapeutic effect on multiple targets and multiple pathways.
Highlights
Rheumatoid arthritis (RA), a common chronic systemic autoimmune disease, is characterized by synovial hyperproliferation and inflammatory/immune cell infiltration [1, 2]
Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) is a unique system pharmacology database of Chinese herbal medicines with data on absorption, distribution, metabolism, and excretion (ADME)-related parameters of herbal ingredients as well as the relationships between diseases, targets, ingredients, and drugs [18]. e active compounds of Huangqi Guizhi Wuwu Decoction (HGWD) were primarily screened based on oral bioavailability (OB) and drug-like (DL) properties, the two important indicators for bioinformatics evaluation of ADME characteristics [19]. e OB is a major pharmacokinetic parameter of oral drugs and is the proportion of oral drug dose in the systemic circulation [20]
A total of 790 compounds of the five herb medicines in HGWD were retrieved from the TCMSP database. is included 87 compounds in Huangqi, 220 in Guizhi, 85 in Baishao, 265 in Shengjiang, and 133 in Dazao
Summary
Rheumatoid arthritis (RA), a common chronic systemic autoimmune disease, is characterized by synovial hyperproliferation and inflammatory/immune cell infiltration [1, 2]. Erefore, it is necessary to explore the potential mechanism of action of HGWD in RA treatment based on network pharmacology and molecular docking methods. E active compounds of HGWD were collected, and their targets were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and DrugBank database, respectively. The compound-target network of HGWD was constructed and visualized through Cytoscape 3.8.0 software. Molecular docking was used to analyze the binding force of the top 10 active compounds with target proteins of VCAM1, CTNNB1, and JUN. E molecular docking results revealed that the top 10 active compounds of HGWD had a strong binding to the target proteins of VCAM1, CTNNB1, and JUN. HGWD has important active compounds such as quercetin, kaempferol, and beta-sitosterol, which exert its therapeutic effect on multiple targets and multiple pathways
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