Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Abstract

Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

Reveals of quercetin’s therapeutic effects on oral lichen planus based on network pharmacology approach and experimental validation

“…Thus, the use of quercetin can correct the immune imbalance by regulating the secretion of Th1 and Th2 cytokines, which is expected to be a new treatment method for OLP. Many reports have demonstrated that decrease in the viability and migration of T lymphocytes, and increase in apoptosis after quercetin treatment is beneficial in the management of inflammatory diseases and cancer 31 , 46 , 47 . Based on our findings, we propose that high concentrations of quercetin inhibit cell proliferation and migration, and induce T lymphocyte apoptosis in OLP patients, which may explain the immunomodulatory effect of quercetin against OLP.…”

“…Network pharmacology is a new method of using bioinformatics to observe the interactions between drugs and diseases, providing a new logical guide and technical routes for the development of drugs 30 . Serval studies have used the network pharmacology to identify the mechanism of action of quercetin and systematically elucidate its role in the treatment of diseases, such as rheumatoid arthritis and Alzheimer's disease 31 , 32 . Unfortunately, there are a few reports on the relationship between quercetin and OLP.…”

A Study Based on Metabolomics, Network Pharmacology, and Experimental Verification to Explore the Mechanism of Qinbaiqingfei Concentrated Pills in the treatment of Mycoplasma Pneumonia

“…It interferes with the transport of eosinophils and is usually produced by a variety of airway cells, especially airway epithelial cells (Kong et al, 2014). MMP9 can be released from activated white blood cells, reduce the level of E-cadherin in lung tissue (Xie X. et al, 2020) and by intervening in the accumulation of neutrophils and eosinophils. It can promote the killing of pathogens and inhibit excessive inflammation (Lu et al, 2008;Kong et al, 2014).…”

“…Network pharmacology can be used to predict the correlation between targets and indications. The molecular docking technology that simulates the molecular structure at the molecular level and the dynamic level verifies the binding status between the targets ( Tang et al, 2020 ). Through the integrated analysis of them, we explore its mechanism of action in the treatment of mycoplasma pneumonia.…”

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

“…Simiao Powder (SMP) is a well-known prescription used in ancient China for the treatment of joint pain [ 9 ]. This prescription originated from Chengfang Biandu in the Qing Dynasty (1904 A.D.).…”