Current and novel therapeutic targets in the treatment of rheumatoid arthritis

George, Genu; Shyni, G. L.; Raghu, Kozhiparambil Gopalan

doi:10.1007/s10787-020-00757-9

Cited by 27 publications

(21 citation statements)

References 173 publications

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“…The cellular mechanisms involved in rheumatoid arthritis are linked to the function of monocytes, macrophages and T cells, the suppressed immune response being a marker of the disease progression [ 146 ]. The strategy used for the inflammation treatment usually involves the neutralization of pro-inflammatory cytokines [ 147 ]. Isoflavones have been shown to suppress inflammation via interaction with various molecular targets [ 12 , 24 , 86 , 148 ].…”

Section: The Role Of Isoflavones In Chronic Degenerative Diseasesmentioning

confidence: 99%

Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases

Bernatonienė

Kazlauskaitė

Kopustinskienė

2021

IJMS

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Isoflavones are phytoestrogens of plant origin, mostly found in the members of the Fabaceae family, that exert beneficial effects in various degenerative disorders. Having high similarity to 17-β-estradiol, isoflavones can bind estrogen receptors, scavenge reactive oxygen species, activate various cellular signal transduction pathways and modulate growth and transcription factors, activities of enzymes, cytokines, and genes regulating cell proliferation and apoptosis. Due to their pleiotropic activities isoflavones might be considered as a natural alternative for the treatment of estrogen decrease-related conditions during menopause. This review will focus on the effects of isoflavones on inflammation and chronic degenerative diseases including cancer, metabolic, cardiovascular, neurodegenerative diseases, rheumatoid arthritis and adverse postmenopausal symptoms.

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Section: The Role Of Isoflavones In Chronic Degenerative Diseasesmentioning

confidence: 99%

Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases

Bernatonienė

Kazlauskaitė

Kopustinskienė

2021

IJMS

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“…The most common biological disease-modifying antirheumatic drugs are TNF-α inhibitors. Despite many drug therapies, the RA patients did not get any significant clinical benefits from these agents [5].…”

Section: Introductionmentioning

confidence: 99%

[Retracted] In Silico Characterization of Growth Differentiation Factors as Inhibitors of TNF‐Alpha and IL‐6 in Immune‐Mediated Inflammatory Disease Rheumatoid Arthritis

Mustafa

Mahrosh

Arif

2021

BioMed Research International

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Tumor necrosis factor alpha (TNF-α) plays a critical role in the progression of inflammation and affects the cells of the synovial membrane. Another key factor in the progression of rheumatoid inflammation is interleukin-6 (IL-6). Both TNF-α and IL-6 promote the proliferation of synovial membrane cells thus stimulating the production of matrix metalloproteinases and other cytotoxins and leading towards bone erosion and destruction of the cartilage. Growth differentiation factor-11 (GDF11) and growth differentiation factor-8 (GDF8) which is also known as myostatin are members of the transforming growth factor-β family and could be used as antagonists to inflammatory responses which are associated with rheumatoid arthritis. In the current study, to elucidate the evolutionary relationships of GDF11 with its homologs from other closely related organisms, a comprehensive phylogenetic analysis was performed. From the phylogram, it was revealed that the clade of Primates that belong to superorder Euarchontoglires showed close evolutionary relationships with order Cetartiodactyla of the Laurasiatheria superorder. Fifty tetrapeptides were devised from conserved regions of GDF11 which served as ligands in protein-ligand docking against TNF-α and IL-6 followed by drug scanning and ADMET profiling of best selected ligands. The peptides SAGP showed strong interactions with IL-6, and peptides AFDP and AGPC showed strong interactions with TNF-α, and all three peptides fulfilled all the pharmacokinetic parameters which are important for bioavailability. The potential of GDF8 as an antagonist to TNF-α and IL-6 was also explored using a protein-protein docking approach. The binding patterns of GDF8 with TNF-α and IL-6 showed that GDF8 could be used as a potential inhibitor of TNF-α and IL-6 to treat rheumatoid arthritis.

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“…On the other hand, hypoxia is associated with immune cell infiltration and synovial hyperplasia. Therefore, the upregulation of synovium-derived HIF-1 α occurs in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA), which are hypoxia-associated diseases [ 54 , 55 ]. HIF-1 α exerts a regulatory role in the function of immune cells.…”

Section: Discussionmentioning

confidence: 99%

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

Fan

Liu

Jin

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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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.

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Current and novel therapeutic targets in the treatment of rheumatoid arthritis

Cited by 27 publications

References 173 publications

Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases

Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases

[Retracted] In Silico Characterization of Growth Differentiation Factors as Inhibitors of TNF‐Alpha and IL‐6 in Immune‐Mediated Inflammatory Disease Rheumatoid Arthritis

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

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