Deciphering the action mechanism of the sacred plant "Ashvattha" (Ficus religiosa L.) in the treatment of delayed-onset muscle soreness

BACKGROUND: DOMS is a common post-exercise syndrome characterized by pain, stiffness, and decreased muscle function. Conventional therapies have limited efficacy and have potential side effects.

OBJECTIVE: This study explored the molecular mechanisms of Ficus religiosa's alleviation of DOMS using network pharmacology, molecular docking, and molecular dynamics simulation analyses.

MATERIALS AND METHODS: This study used a network pharmacology framework to identify and analyze the phytochemicals from F. religiosa. Databases like IMPPAT 2.0 were used to retrieve potential compounds, while SwissTargetPrediction predicted target proteins. Therapeutic targets were identified using Genecards and OMIM databases. Protein-protein interaction networks were analyzed using STRING and Cytoscape software, while pathway enrichment was conducted using Enrichr. Molecular docking was performed using AutoDockTools (v1.5.7), followed by molecular dynamics simulations using GROMACS to validate target-compound interactions.

RESULTS: Of the 140 phytochemicals, 44 met the drug-likeness and bioavailability criteria and were associated with 39 potential therapeutic targets for DOMS. KEGG enrichment analysis revealed inflammation, oxidative stress, and immune regulation as the primary mechanisms of action. Prostaglandin-endoperoxide synthase 2 (PTGS2) was identified as a critical target. Molecular docking showed that compounds such as α-eudesmol, epi-γ-eudesmol, and α-cadinol exhibited superior binding affinities for PTGS2 compared to ibuprofen. Finally, molecular dynamics simulation demonstrated that α-cadinol exhibited the most stable binding owing to its robust hydrogen bonding, whereas epi-α-cadinol displayed progressive stabilization and efficient accommodation inside the active region of the protein.

CONCLUSION: This study suggests that F. religiosa could be used as a therapeutic agent for the management of DOMS. The key compounds, α-cadinol and epi-α-cadinol, show potential anti-inflammatory and analgesic effects.