Comparative In-silico Evaluation of Therapeutic Potential of Thymus serpyllum and Tachyspermum ammi against Rheumatoid Arthritis

Abstract

Rheumatoid arthritis is an autoimmune, symmetrical polyarthritis characterized by synovial hyperplasia leading to progressive bone and cartilage degeneration. In this study, two medicinal plants namely Thymus serpyllum and Tachyspermum ammi have been compared for their anti-arthritic potential against rheumatoid arthritis through radical scavenging DPPH assay, albumin denaturation assay and human red blood cell membrane stabilization assay followed by examining their modes of action using in-silico approach. Potentially active compounds from GCMS analysis of methanolic extracts of both plants were screened on the basis of Lipinski rule of 5, ADMET properties and blood brain barrier permeability by utilizing data from online servers like swissADME and admetSAR. Hub gene analysis was done on potential targets of rheumatoid arthritis taken from Therapeutic Target Database (TTD) and two hub genes i.e Tumor Necrosis Factor alpha (TNF α) and Vascular Endothelial Growth Factor A (VEGF-A) were recruited as a result by using String and Cytoscape. All the shortlisted compounds from plant extracts were docked with proteins, TNF-α and VEGF-A and the compounds which exhibited least binding energies with both of the proteins were chosen. Two compounds of Thymus serpyllum i.e Erythronolide A, 12-deoxy showed good binding energy with TNF alpha where as 5-[5-(Trifluoromethyl)isoxazol-3-yl]thiophene-2-sulfonyl chloride exhibited good binding energy with VEGFA. Similarly, two compounds of Tachyspermum ammi i.e. Methyl 2-hydroxy-5-[(4-methylpiperazin-1-yl)methyl]benzoate showed least binding energy with TNF alpha and S-2-[2-Norbornylamino]ethyl thiosulfuric acid with that of VEGFA. Results employ that methanolic extracts of both plants exhibited good anti-arthritic potential whereas Thymus serpyllum showed more potent anti-arthritic potential than Tachyspermum ammi. In-silico analysis further revealed that compounds of Thymus serpyllum showed better binding energies with both hub genes as compared to Tachyspermum ammi. In conclusion, Thymus serpyllum is a much more potent anti-arthritic medicinal plant than Tachyspermum ammi and can be further tested using in-vitro and in-vivo approaches.