Reiya Bosco Don Bosco, Johnson Retnaraj Samuel Selvan Christyraj, Beryl Vedha Yesudhason
{"title":"促智草药作为阿尔茨海默病有效治疗药物的协同作用:化学信息学、药代动力学和系统药理学方法。","authors":"Reiya Bosco Don Bosco, Johnson Retnaraj Samuel Selvan Christyraj, Beryl Vedha Yesudhason","doi":"10.1177/25424823241307019","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which subdues over 55 million people and finding a cure, still remains disenchanting. Indian medicinal herbs notably, <i>Withania somnifera</i>, <i>Bacopa monnieri</i>, <i>Curcuma longa</i>, and <i>Clitoria ternatea</i> are traditionally utilized for their memory-enhancing properties.</p><p><strong>Objective: </strong>We computationally investigated the therapeutic potential of four nootropic herbs by uncovering the molecular mechanisms underlying their treatment for AD.</p><p><strong>Methods: </strong>Cheminformatics, pharmacokinetics, and system pharmacology studies were carried out to predict the phytocompounds drug-like properties, protein targets, targets functional association and enrichment analysis. A comparative study was performed with phytocompounds and FDA-approved drugs. Investigation on the expression of protein targets in the hippocampus and entorhinal cortex of the AD brain was performed. Network was constructed to depict the interaction between phytocompounds, drugs, and molecular targets.</p><p><strong>Results: </strong>Through comparative analysis, we found that the phytocompounds shared common targets with both FDA drugs and drugs under clinical trials. We identified potential active compounds notably, Withaferin A, Withanolide-D, Withanolide-E, Withanolide-G, and Humulene epoxide II, that can combat AD. Interestingly, the enzyme inhibition scores of the identified drugs were much higher than FDA-approved drugs. In addition, regulatory proteins such as AβPP, acetylcholinesterase, BACE1, and PTPN1 were the targets of 8, 16, 9, and 22 phytocompounds, respectively. Nonetheless, AR and CYP19A, were the primary targets of most phytocompounds.</p><p><strong>Conclusions: </strong>Herbal medicines can synergistically stimulate multiple protein targets, rendering a holistic and integrative treatment, encouraging a promising avenue to treat AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1745-1762"},"PeriodicalIF":2.8000,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863741/pdf/","citationCount":"0","resultStr":"{\"title\":\"Synergistic activity of nootropic herbs as potent therapeutics for Alzheimer's disease: A cheminformatics, pharmacokinetics, and system pharmacology approach.\",\"authors\":\"Reiya Bosco Don Bosco, Johnson Retnaraj Samuel Selvan Christyraj, Beryl Vedha Yesudhason\",\"doi\":\"10.1177/25424823241307019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which subdues over 55 million people and finding a cure, still remains disenchanting. Indian medicinal herbs notably, <i>Withania somnifera</i>, <i>Bacopa monnieri</i>, <i>Curcuma longa</i>, and <i>Clitoria ternatea</i> are traditionally utilized for their memory-enhancing properties.</p><p><strong>Objective: </strong>We computationally investigated the therapeutic potential of four nootropic herbs by uncovering the molecular mechanisms underlying their treatment for AD.</p><p><strong>Methods: </strong>Cheminformatics, pharmacokinetics, and system pharmacology studies were carried out to predict the phytocompounds drug-like properties, protein targets, targets functional association and enrichment analysis. A comparative study was performed with phytocompounds and FDA-approved drugs. Investigation on the expression of protein targets in the hippocampus and entorhinal cortex of the AD brain was performed. Network was constructed to depict the interaction between phytocompounds, drugs, and molecular targets.</p><p><strong>Results: </strong>Through comparative analysis, we found that the phytocompounds shared common targets with both FDA drugs and drugs under clinical trials. We identified potential active compounds notably, Withaferin A, Withanolide-D, Withanolide-E, Withanolide-G, and Humulene epoxide II, that can combat AD. Interestingly, the enzyme inhibition scores of the identified drugs were much higher than FDA-approved drugs. In addition, regulatory proteins such as AβPP, acetylcholinesterase, BACE1, and PTPN1 were the targets of 8, 16, 9, and 22 phytocompounds, respectively. Nonetheless, AR and CYP19A, were the primary targets of most phytocompounds.</p><p><strong>Conclusions: </strong>Herbal medicines can synergistically stimulate multiple protein targets, rendering a holistic and integrative treatment, encouraging a promising avenue to treat AD.</p>\",\"PeriodicalId\":73594,\"journal\":{\"name\":\"Journal of Alzheimer's disease reports\",\"volume\":\"8 1\",\"pages\":\"1745-1762\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-12-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863741/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Alzheimer's disease reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/25424823241307019\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Alzheimer's disease reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/25424823241307019","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Synergistic activity of nootropic herbs as potent therapeutics for Alzheimer's disease: A cheminformatics, pharmacokinetics, and system pharmacology approach.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which subdues over 55 million people and finding a cure, still remains disenchanting. Indian medicinal herbs notably, Withania somnifera, Bacopa monnieri, Curcuma longa, and Clitoria ternatea are traditionally utilized for their memory-enhancing properties.
Objective: We computationally investigated the therapeutic potential of four nootropic herbs by uncovering the molecular mechanisms underlying their treatment for AD.
Methods: Cheminformatics, pharmacokinetics, and system pharmacology studies were carried out to predict the phytocompounds drug-like properties, protein targets, targets functional association and enrichment analysis. A comparative study was performed with phytocompounds and FDA-approved drugs. Investigation on the expression of protein targets in the hippocampus and entorhinal cortex of the AD brain was performed. Network was constructed to depict the interaction between phytocompounds, drugs, and molecular targets.
Results: Through comparative analysis, we found that the phytocompounds shared common targets with both FDA drugs and drugs under clinical trials. We identified potential active compounds notably, Withaferin A, Withanolide-D, Withanolide-E, Withanolide-G, and Humulene epoxide II, that can combat AD. Interestingly, the enzyme inhibition scores of the identified drugs were much higher than FDA-approved drugs. In addition, regulatory proteins such as AβPP, acetylcholinesterase, BACE1, and PTPN1 were the targets of 8, 16, 9, and 22 phytocompounds, respectively. Nonetheless, AR and CYP19A, were the primary targets of most phytocompounds.
Conclusions: Herbal medicines can synergistically stimulate multiple protein targets, rendering a holistic and integrative treatment, encouraging a promising avenue to treat AD.