Phytotherapeutic potential of compounds identified from fractionated extracts of Morus alba L., as an inhibitor of interleukin-6 in the treatment of rheumatoid arthritis: computational approach

The presence of HLA-DRB1 alleles that encode critical points associated with environmental interactions is associated with increased risk of rheumatoid arthritis caused by anti-citrullinated protein antibodies. Therefore, interleukin-6 (IL-6), a multifunctional cytokine that controls both local and systemic acute inflammatory responses through its ability to induce a phase response, plays a serious role. Its overexpression leads to pathological challenges such as rheumatoid arthritis and menopausal osteoporosis. However, targeting the IL-6 receptor and its region could be the major step in controlling the overexpression of this cytokine for therapeutic importance. Therefore, our research explored the computational insight needed to investigate the anti-RFA potential of phytochemicals from fractionated extracts of Morus alba L. against receptors, which have been implicated as druggable targets for the treatment of rheumatoid arthritis. In this study, fifty-nine (59) previously isolated and characterized phytochemicals from M. alba L. were identified from the literature and retrieved from the PubChem database. In silico screening was used to assess the mode of action of these phytochemicals from M. alba L. against receptors that may serve as therapeutic targets for rheumatoid arthritis. Molecular docking studies, toxicity prediction, drug visualization and molecular dynamics simulation (MD) of the ligands together with the receptor-identified target were carried out using the Schrodinger Molecular Drug Discovery Suite. The findings indicated that a selected group of ligands displayed significant binding strength to specific amino acid residues, revealing an important link between the building blocks of proteins (amino acids) and ligands at the inhibitor binding site through traditional chemical interactions, such as interactions between hydrophobic and hydrogen bonds. The binding affinities of the receptors were carefully checked via comparison with those of the approved ligands, and the results suggested structural and functional changes in the lead compounds. Therefore, the bioactive component from M. alba L. could be a lead foot interleukin-6 (IL-6) inhibitor and could be a promising lead compound for the treatment of rheumatoid arthritis and related challenges.