{"title":"Investigating the aging-modulatory mechanism of Rasayana Churna, an Ayurvedic herbal formulation, using a computational approach.","authors":"Amisha Bisht, Anita Nayal, Disha Tewari, Sanjay Kumar, Subhash Chandra","doi":"10.1007/s10522-025-10188-0","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"26 2","pages":"53"},"PeriodicalIF":4.4000,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-025-10188-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments.
Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.