Identification of Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking

Abstract

Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking.Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA–WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP–RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α.Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis.Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.

Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway

“…The PPI network map was constructed for the curated databases, experimental determined, co-expression, fusion, neighborhood, and co-localization of potential target genes with predicted gene interactions [ 33 ]. The common targets were put into the STRING database where the organism was set as ‘Homo sapiens’, and The PPI network with a medium confidence score > 0.4 was selected and imported into Cytoscape software version 3.8.2 for interaction network visualization [ 34–37 ].…”

An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding

“…Oroxylin A from Scutellariae Radix (drug 4) demonstrated binding to the ACE2 receptor on human embryonic kidney (HEK293T) cells and prevented SARS-CoV-2 from entering the cells [ 55 ]. Paeoniae Radix Alba (drug 9) is a 3CLpro inhibitor and it contains kaempferol and beta-sitosterol both of which inhibit SARS-CoV2 [ 56 ]. Berberine from Coptidis Rhizoma (drug 2) was also reported to have potential inhibitory activity on COVID-19 Mpro [ 57 ].…”

Adipose-Derived Stem Cell Exosomes as a Novel Anti-Inflammatory Agent and the Current Therapeutic Targets for Rheumatoid Arthritis

“…Some of these drugs are monoclonal, chimeric humanized fusion antibodies. Newer bDMARDs, with various modes of action, can be administered to RA patients who are unresponsive to TNF-inhibitor treatment [ 54 ]. For instance, abatacept (ABT, which interrupts the costimulation molecule signal between T and B cells) [ 55 ], rituximab (RTX, which targets CD20 + B cells) [ 56 ], and tocilizumab (TCZ, which is an IL-6 receptor (IL-6R) antagonist) [ 57 ] have demonstrated high treatment efficacy in patients with active RA, particularly in those with inadequate responses to TNF-inhibitor treatment [ 58 ].…”