Integrated Molecular Docking with Network Pharmacology to Reveal the Molecular Mechanism of Simiao Powder in the Treatment of Acute Gouty Arthritis

Yihua Fan; Wei Liu; Yue Jin; Xu Hou; Xuewu Zhang; Hudan Pan; Hang Lu; Xiaojing Guo

doi:10.1155/2021/5570968

Integrated Molecular Docking with Network Pharmacology to Reveal the Molecular Mechanism of Simiao Powder in the Treatment of Acute Gouty Arthritis

Evid Based Complement Alternat Med. 2021 Apr 27:2021:5570968. doi: 10.1155/2021/5570968. eCollection 2021.

Authors

Yihua Fan^{1

2}, Wei Liu^{1

2}, Yue Jin^{1

2}, Xu Hou³, Xuewu Zhang⁴, Hudan Pan⁵, Hang Lu^{1

2}, Xiaojing Guo^{1

2}

Affiliations

¹ First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
² National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
³ Department of Endocrinology and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China.
⁴ Department of Rheumatology, People Hospital of Beijing University, Bejing 100044, China.
⁵ Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao 999078, China.

Abstract

Background: The incidence of gout has been rapidly increasing in recent years with the changing of diet. At present, modern medications used in the clinical treatment of gout showed several side effects, such as gastrointestinal damage and the increased risk of cardiovascular disease. The traditional Chinese prescription Simiao Powder (SMP) has a long history in the treatment of acute gouty arthritis (AGA) and has a good curative effect. However, the mechanism and target of its therapeutic effects are still not completely understood.

Methods: Potential active compounds (PACs) and targets of SMP were found in the TCMSP database, and the disease target genes related to AGA were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, TTD, OMIM, and PharmGKB disease databases with "acute gouty arthritis" and "Arthritis, Gouty" as keywords, respectively. The network of "Traditional Chinese medicine (TCM)-PACs-potential targets of acute gouty arthritis" was constructed with the Cytoscape 3.7.2 software, and the target genes of acute gouty arthritis were intersected with genes regulated by active compounds of SMP. The resultant common gene targets were input into Cytoscape 3.7.2 software, and the BisoGenet plug-in was used to construct a PPI network. The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersecting target proteins were performed using R software and corresponding program packages. The molecular docking verification was carried out between the potentially active compounds of SMP and the core target at the same time.

Results: 40 active components and 203 targets were identified, of which 95 targets were common targets for the drugs and diseases. GO function enrichment analysis revealed that SMP regulated several biological processes, such as response to lipopolysaccharide and oxidative stress, RNA polymerase II transcription regulator complex, protein kinase complex, and other cellular and molecular processes, including DNA-binding transcription factor binding. Results of KEGG pathway analysis showed that SMP was associated with AGA-related pathways such as interleukin-17 (IL-17), tumor necrosis factor (TNF), p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. The results of molecular docking showed that active compounds in SMP exhibited strong binding to five core protein receptors (TP53, FN1, ESR1, CDK2, and HSPA5).

Conclusions: Active components of SMP, such as quercetin, kaempferol, wogonin, baicalein, beta-sitosterol, and rutaecarpine, showed therapeutic effects on AGA. These compounds were strongly associated with core target proteins (such as TP53, FN1, ESR1, CDK2, and HSPA5). This study reveals that IL-17, TNF, p53, and HIF-1 signaling pathways mediate the therapeutic effects of SMP on AGA. These findings expand our understanding of the mechanism of SMP in the treatment of AGA.