Mechanism of Guizhi Shaoyao Zhimu Decoction in the Treatment of Rheumatoid Arthritis-Interstitial Lung Disease Based on Network Pharmacology and Molecular Docking Technology
ZHANG Ning, GUO Yali, LIU Jian, et al. Mechanism of Guizhi Shaoyao Zhimu Decoction in the Treatment of Rheumatoid Arthritis-Interstitial Lung Disease Based on Network Pharmacology and Molecular Docking Technology[J]. 2022,22(10):1157-1163.
ZHANG Ning, GUO Yali, LIU Jian, et al. Mechanism of Guizhi Shaoyao Zhimu Decoction in the Treatment of Rheumatoid Arthritis-Interstitial Lung Disease Based on Network Pharmacology and Molecular Docking Technology[J]. 2022,22(10):1157-1163. DOI: 10.14009/j.issn.1672-2124.2022.10.002.
OBJECTIVE: To probe into the mechanism of Guizhi Shaoyao Zhimu decoction in the treatment of rheumatoid arthritis-interstitial lung disease(RA-ILD) based on network pharmacology and molecular docking technology
so as to lay the theoretical foundation for the follow-up mechanism research. METHODS: Traditional Chinese medicine systems pharmacology database and analysis platform was used to search the effective components and target genes of Guizhi Shaoyao Zhimu decoction. Corresponding standardized treatment was performed on the target genes. GeneCard
PharmGkb and Online Mendelian Inheritance in Man databases were used to obtain the target genes of diseases. Potential target genes of drugs and diseases were intersected and visualized in the form of Venn diagram. Cytoscape 3.8.0 software was used to screen and construct the “drug active components-disease core targets” network
and the protein-protein interaction(PPI) network was constructed in STRING database. Analysis was performed by gene ontology(GO) functional enrichment and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The main active components and core targets of the drug were verified by molecular docking using Vina software. RESULTS: A total of 141 active components and 166 targets of Guizhi Shaoyao Zhimu decoction in the treatment of RA-ILD were screened through the database. The main active components included quercetin
kaempferol and luteolin. A total of 17 core target genes including signal transducer and activator of transcription 3(STAT3)
protein kinase B(Akt)1
mitogen-activated protein kinase(MAPK)1 and MAPK3 were identified by PPI network topology screening. A total of 2 762 enrichment results were obtained by GO enrichment analysis
including 2 467 biological processes
87 cellular components and 208 molecular functions. After KEGG pathway enrichment analysis
a total of 170 pathways enrichment results were obtained
mainly interleukin-17 signaling pathway
tumor necrosis factor signaling pathway
phosphatidylinositol 3-kinase-Akt signaling pathway and JAK kinase-STAT signaling pathway. The final docking results showed that the main active components could bind to the key core targets and showed good affinity. CONCLUSIONS: Guizhi Shaoyao Zhimu decoction can treat RA-ILD through multiple targets
involving multiple signaling pathways and biological processes. The combination of quercetin
luteolin
kaempferol and wogonin with STAT3
Akt1
MAPK1 and MAPK3 may be one of the important mechanisms.