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

Abstract

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.

[Retracted] Identification of Peptides as Novel Inhibitors to Target IFN‐γ, IL‐3, and TNF‐α in Systemic Lupus Erythematosus

“…TNF- α is a proinflammatory cytokine, belongs to the super family of tumor necrosis factor, and secreted by macrophages in a defense mechanism to protect from damage by inducing inflammation against pathogenic stimuli. The elevated level or mutation in TNF- α signaling leads towards deleterious consequences including many autoimmune disorders [ 25 ].…”

Investigation of Plant Antimicrobial Peptides against Selected Pathogenic Bacterial Species Using a Peptide-Protein Docking Approach

“…Computer-aided drug designing using molecular docking and molecular dynamics simulation approaches provides rapid screening of novel and potential drug candidates to predict drug-receptor interactions [ 46 ]. In recent years, plant-derived natural compounds have been proved as potent drug candidates and inhibitors of many pathogenic proteins that play crucial roles in the pathogenesis of various diseases [ 47 ]. Recently, using computational modeling, the molecular dynamics aspects of moxifloxacin-induced resistance in M .…”

Antioxidant and Antineuroinflammatory Mechanisms of Kaempferol-3-O-β-d-Glucuronate on Lipopolysaccharide-Stimulated BV2 Microglial Cells through the Nrf2/HO-1 Signaling Cascade and MAPK/NF-κB Pathway

“…The increase in the level of pro-inflammatory cytokines follows a similar pattern to the production of ROS . Moreover, pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α play an important role in inducing neurodegeneration in the CNS. , IL-6 and TNF-α are pro-inflammatory cytokines that are produced at an early stage, and their raised levels can be found in a variety of inflammatory diseases . Overexpression of pro-inflammatory cytokines can be regarded as an indicator of neurological disease in the brain. , Using a natural product such as K3G is a promising therapy in neuroinflammation because it could block pro-inflammatory cytokines.…”