Investigating the aging-modulatory mechanism of Rasayana Churna, an Ayurvedic herbal formulation, using a computational approach.

This study investigates the impact and mechanisms of Rasayana Churna, an Ayurvedic poly-herbal formulation, in treating aging-related disorders through text mining, network pharmacology, molecular docking simulation, Super-MMPBSA, and density functional theory. The text mining of Rasayana Churna highlighted the diverse therapeutic potential of Phyllanthus emblica, Tinospora cordifolia, and Tribulus terrestris in managing aging-related disorders through their antidiabetic, antioxidant, and anti-inflammatory properties. Using network pharmacology, 17 bioactive compounds and 137 corresponding potential targets of Rasayana Churna were identified and used to construct protein-protein interaction and hub gene networks. Key targets such as AKT1, BCL2, ESR1, and GSK3B were linked to aging-related pathways, with GO and KEGG enrichment analyses highlighting processes like apoptosis, oxidative stress response, and pathways like PI3K-Akt signaling. Molecular docking analysis identified 14 compounds with strong binding affinity toward the key aging target AKT1. Three bioactive compounds-Kaempferol, N-Caffeoyltyramine, and Multifidol glucoside-exhibited superior stability and binding interactions in MD simulations, confirmed by RMSD, RMSF, Rg, hydrogen bonding, SASA, PCA, and free energy landscape analysis. Super-MMPBSA (last 30 ns) calculation was performed to analyze dynamic behavior and protein-ligand stability, revealing significantly lower ΔG binding free energy values for the three hit compounds (- 177.871, - 164.855, - 199.649 kJ/mol, respectively) compared to the AKT1-reference complex (- 109.463 kJ/mol). DFT analysis revealed favorable electronic properties and kinetic stability for these compounds. Integrating traditional Ayurvedic knowledge with computational techniques suggests Rasayana Churna could prevent and manage aging-related conditions. However, further in vitro, in vivo, and clinical studies are needed to validate its aging-modulatory potential.