GC-MS Analysis and In-silico Molecular Docking of Phytoconstituents of Sansevieria roxburghiana against IL-1β and TNF-α for Anti-Rheumatic Activity

Abstract

Background: Rheumatoid arthritis (RA) is recognized as a long-term inflammatory form of arthritis. This inflammation becomes long-lasting, and the synovial tissue thickens as a result of increased cell activity, protein production, and other variables in the joint, causing discomfort, redness, and warmth. It can also harm the joints of the hands, wrists, fingers, elbows, shoulders, toes, spinal column, and knees. Due to the autoimmune response, there is an aberrant production of inflammatory mediators such as Tumour necrosis factor- alpha (TNF-a), Interleukins (IL-1, IL-6,                IL-7, IL-15, IL-17, IL-18, and IL-23), Granulocyte-macrophage colony-stimulating factor (GM-CSF), and Interferon (IFN)-ϒ. By inhibiting their production, those inflammatory mediators will play a pivotal role in the therapy of RA. Purpose of the Study: The goal of the current study was to explore the anti-rheumatic activity of Sansevieria roxburghiana using the computational docking method.  Research Rationale: Administration of Non-steroidal anti-inflammatory drugs, steroidal medicaments, and Disease-modifying anti-rheumatoid therapies creates substantial adverse effects in people suffering with RA. To overcome the burdens and toxicity of drug products herbal medicines were taken into the field of research.  Materials and Methods: For this, 14 bioactive compounds from ethanolic extract of S. roxburghiana leaves were identified using the GC-MS (Gas chromatography-mass spectrometry) study and utilized as a binding compound (ligand) for biological target interactions. The crystallographic geometries of two targeted molecules, Interleukin-1β (IL-1β) and Tumour necrosis factor-alpha (TNF-α), have been retrieved from the PDB database. Methotrexate, a well-known medication for IL-1β and TNF-α inhibitors, was chosen as the reference for the comparative analysis. Computational docking was performed using the Autodock4 (version 1.5.6) choice based on the score functions. Results: The results displayed the binding energy as follow -10.13, -9.77, -8.98 and -8.67 Kcal/mol of 2-isopropyl-5 methyl cyclohexyl 3-(1-(4-chlorophenyl)-3-oxobutyl)-C, 3-chloro-5-cholestene, stigmasterol, and cycloartanol against IL-1 β (PDB ID: 4GAI) and standard methotrexate was -8.14 Kcal/mol. For TNF-α (PDB ID: 5M2J) the binding energy is -8.94, -8.85, -8.46, and -8.24 Kcal/mol of cycloartanol, stigmasterol, 2-isopropyl-5 methyl cyclohexyl 3-(1-(4-chlorophenyl)-3-oxobutyl)-C and 3-chloro-5-cholestene by with comparing methotrexate (-8.89 Kcal/mol).  Conclusion: Hence, it was indicated that the phytoconstituents of S. roxburghiana could serve as a potential approach for designing future antirheumatic drugs.