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

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.

Exploration of molecular targets and mechanisms of Chinese medicinal formula Acacia Catechu ‐Scutellariae Radix in the treatment of COVID‐19 by a systems pharmacology strategy

“…The 2D image of molecular docking depicts the binding mode between the core target protein and the compound as well as the interaction with the surrounding amino acid residues. The main forces between ligand and protein are hydrophobic force and hydrogen bond, which both are chemical bonds with strong binding force (Fan et al, 2021 ). For instance, Beta‐sitosterol bounded to Akt1, had hydrophobic interactions with Phe150, Tyr184, Pro187, Ile156, Met176, Phe230, Met166, Ala162, His152, Leu110, and Pro147 (Figure 6a ).…”

“…We collected different genes associated with COVID‐19 from four resources (Fan et al, 2021 ). (1) Human Gene Database (GeneCards, ( https://www.genecards.org/ ), (2) Therapeutic Target Database (TTD, http://db.idrblab.net/ttd/ ), (3) Comparative Toxicogenomics Database (CTD, http://ctdbase.org/ ), and (4) DisGeNET database ( https://www.disgenet.org/ ).…”

“…Meanwhile, ritonavir, Nirmatrelvir, a potent SARS‐CoV‐2 3CLpro protease inhibitor (Reina & Iglesias, 2020 ), and SSAA09E2, an inhibitor of ACE2 (Bibi, Gul, Ali, & Kamal, 2021 ), were taken as positive control. The binding energy ≤0 kcal/mol indicated that the compound could bind and interact with the target, whereas the binding energy <−5 kcal/mol demonstrated a very strong binding force (Fan et al, 2021 ).…”

Virtual Screening–Molecular Docking–Activity Evaluation of Ailanthus altissima (Mill.) Swingle Bark in the Treatment of Ulcerative Colitis

“…Molecular docking technology docks known small-molecule active substances with related target proteins, which can clarify the mechanism of action between active ingredients of TCM and targets at the molecular level [31,32]. At present, molecular docking technology plays an important role in elucidating the mechanism of action between active ingredients of TCM and related target proteins in many diseases, such as cardiovascular disease [20] and cancer [21].…”

Screening of anti‑chronic nonbacterial prostatitis activity of different extractions of the aerial part of Glycyrrhiza uralensis, and network pharmacology research

“…The targets of the chemical components and CNP were uploaded into the Cytoscape plug-in Bisogenet ( 24 ) to expand the target. The intersecting targets of the expanded chemical components and CNP were selected.…”