Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments

作者：Zeng, Liying; Lin, Zekun; Kang, Pan; Zhang, Meng; Tang, Hongyu; Li, Miao; Xu, Kun; Liu, Yamei; Jiang, Ziyun^*; Huo, Shaochuan^*

来源：Evidence-based Complementary and Alternative Medicine, 2022, 2022: 2322417.

DOI：10.1155/2022/2322417

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• INFLAMMATION
• MANAGEMENT
• DISEASE

Background. This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immunein"ammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1") inhibitors by using network pharmacology, molecular docking, and cell experiments. Methods. In this study, the compounds of TFDC and the potential in"ammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic eoects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1" in GA. Molecular docking technology was used to analyze the optimal eoective compounds from the TFDC for docking with IL-1". Result. 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA in"ammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA in"ammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-in"ammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1" mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1" inhibitor. Conclusion. Our findings provide an essential role and bases for further immune-in"ammatory studies on the molecular mechanisms of TFDC and IL-1" inhibitors development in GA.

• 单位
  广州中医药大学; 郑州大学; 1