Network pharmacology based anti – inflammatory activity of Datura (Datura metel L.): an In-silico study

Background: Rheumatoid arthritis (RA), is a chronic autoimmune disease, which is having the symptoms joint pain, swelling, and gradual joint destruction by refractory joint inflammation. Even though the current available treatments are effective in managing and reducing the progression of the disease but these interventions are associated with severe complications. Datura metel L., is a shrub which is known for its therapeutic potential in Ayurveda for the treatment of a variety of inflammatory conditions like arthritis. Objective: A network pharmacology-based study was planned to validate Ayurveda knowledge and to understand the mechanism of action of Datura in inflammation. Materials and Methods: The databases like Dr. Dukes, PubChem, Gene Cards and IMPPAT were utilised to identify the potential targets and related pathways. The open-source databases revealed 14 phytocompounds in Datura and the Swiss target Prediction Server predicted 79 target protein molecules. The STRING 10.5, KEGG Pathway database and Cytoscape 3.7.2 were utilised in the network pharmacology study for identifying protein targets, potential interactions, pathway analysis and for the construction of the network. Results: 14 phytocompounds identified in Datura which were expected to be targeting 79 inflammatory proteins. The gene enrichment analysis identified 27 targets among which The MAPK signaling pathway acts as the key hub. The majority of compounds fulfilled acceptable standards in drug-likeness screening. The phytocompounds Atropine (1.39) and Hyoscyamine (1.29) shows high score according to drug-likeness screening which predicts the suitability of the compounds as a drug in the disease. Conclusion: The study concludes that the phytocompounds like hyoscyamine, deoxywithastramonolide, fastusic acid, scopolamine, and tigloidine have major action on TNF, IL6, COX, APK14, and other proteins through P38 MAPK signalling pathway and the Rheumatoid arthritis pathway. The network pharmacology study validates the anti-inflammatory potential of Datura metel.