基于网络的方法探讨钩藤生物碱治疗高血压和缓解阿尔茨海默病的机制。

PubMed ID
G H
发表日期 2020年Mar月

原始出处 国际分子科学杂志
International journal of molecular sciences
作者 Wu  Wenyong  Zhang  Zijia  Li  Feifei  Deng  Yanping  Lei  Min  Long  Huali  Hou  Jinjun  Wu  Wanying 

文献标题 基于网络的方法探讨钩藤生物碱治疗高血压和缓解阿尔茨海默病的机制。
A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer's Disease.
A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer's Disease.

文献摘要

钩藤生物碱是钩藤属植物的主要生物活性物质,在中医药治疗心血管和精神疾病方面有着悠久的临床应用历史。然而,目前对钩藤生物碱的多靶点、多途径和生物活性的认识还存在差距。网络药理学通过构建药物-靶点-疾病之间的相互作用,为呈现药物、潜在靶点和相关途径之间的复杂联系提供了系统的方法学和新的视角。这对于研究多适应证中药以及这些多适应证药物如何受到生物系统中复杂相互作用的影响是一个很有价值的工具。为了更好地了解钩藤生物碱的作用机制和作用靶点,我们构建了一个基于网络药理学的综合分析平台,包括靶点预测、蛋白质-蛋白质相互作用(PPI)网络、拓扑分析、基因富集分析和分子对接。利用这个平台,我们揭示了钩藤生物碱抗高血压作用的潜在机制,并探讨了钩藤生物碱在预防阿尔茨海默病中的可能应用。利用生物学实验对这些结果进行了进一步的评价和完善。我们的研究为理解中医药的整体药理学以及探索中医药在传统应用之外的多适应证特性提供了一种新的策略。


Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein-protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids' anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer's disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.

Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein-protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids' anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer's disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.


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