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

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Amisha Bisht, Anita Nayal, Disha Tewari, Sanjay Kumar, Subhash Chandra
{"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.

本研究通过文本挖掘、网络药理学、分子对接模拟、Super-MMPBSA 和密度泛函理论,研究了阿育吠陀多草药配方 Rasayana Churna 在治疗衰老相关疾病方面的影响和机制。通过对 Rasayana Churna 的文本挖掘,我们发现了白皮松、虎杖和刺蒺藜在抗糖尿病、抗氧化和抗炎方面的多种治疗潜力。利用网络药理学,我们确定了 Rasayana Churna 的 17 种生物活性化合物和 137 个相应的潜在靶点,并利用它们构建了蛋白质-蛋白质相互作用和枢纽基因网络。AKT1、BCL2、ESR1和GSK3B等关键靶点与衰老相关通路有关,GO和KEGG富集分析突出了细胞凋亡、氧化应激反应等过程和PI3K-Akt信号转导等通路。分子对接分析发现,有 14 种化合物与关键的衰老靶标 AKT1 具有很强的结合亲和力。三种生物活性化合物--山奈酚、N-咖啡酰基酪胺和多菲醇葡萄糖苷--在 MD 模拟中表现出卓越的稳定性和结合相互作用,并得到 RMSD、RMSF、Rg、氢键、SASA、PCA 和自由能景观分析的证实。与 AKT1 参考复合物(- 109.463 kJ/mol)相比,三个命中化合物的ΔG 结合自由能值明显较低(分别为 - 177.871、- 164.855 和 - 199.649 kJ/mol)。DFT 分析表明,这些化合物具有良好的电子特性和动力学稳定性。将传统的阿育吠陀知识与计算技术相结合,表明 Rasayana Churna 可以预防和控制与衰老有关的疾病。不过,还需要进一步的体外、体内和临床研究来验证其调节衰老的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信