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从靶点网络角度看抗阿尔茨海默病草药的生物信息学分析。

Towards a bioinformatics analysis of anti-Alzheimer's herbal medicines from a target network perspective.

机构信息

School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.

出版信息

Brief Bioinform. 2013 May;14(3):327-43. doi: 10.1093/bib/bbs025. Epub 2012 Aug 11.

Abstract

With the growth of aging population all over the world, a rising incidence of Alzheimer's disease (AD) has been recently observed. In contrast to FDA-approved western drugs, herbal medicines, featured as abundant ingredients and multi-targeting, have been acknowledged with notable anti-AD effects although the mechanism of action (MOA) is unknown. Investigating the possible MOA for these herbs can not only refresh but also extend the current knowledge of AD pathogenesis. In this study, clinically tested anti-AD herbs, their ingredients as well as their corresponding target proteins were systematically reviewed together with applicable bioinformatics resources and methodologies. Based on above information and resources, we present a systematically target network analysis framework to explore the mechanism of anti-AD herb ingredients. Our results indicated that, in addition to the binding of those symptom-relieving targets as the FDA-approved drugs usually do, ingredients of anti-AD herbs also interact closely with a variety of successful therapeutic targets related to other diseases, such as inflammation, cancer and diabetes, suggesting the possible cross-talks between these complicated diseases. Furthermore, pathways of Ca(2+) equilibrium maintaining upstream of cell proliferation and inflammation were densely targeted by the anti-AD herbal ingredients with rigorous statistic evaluation. In addition to the holistic understanding of the pathogenesis of AD, the integrated network analysis on the MOA of herbal ingredients may also suggest new clues for the future disease modifying strategies.

摘要

随着全球老龄化人口的增长,最近观察到阿尔茨海默病(AD)的发病率不断上升。与 FDA 批准的西药相比,草药以丰富的成分和多靶点为特色,具有显著的抗 AD 作用,尽管其作用机制(MOA)尚不清楚。研究这些草药的可能 MOA 不仅可以更新,而且可以扩展 AD 发病机制的现有知识。在这项研究中,系统地综述了经过临床测试的抗 AD 草药、其成分以及相应的靶蛋白,并结合了适用的生物信息学资源和方法。基于上述信息和资源,我们提出了一个系统的靶标网络分析框架,以探索抗 AD 草药成分的作用机制。我们的结果表明,除了像 FDA 批准的药物那样与那些缓解症状的靶标结合外,抗 AD 草药的成分还与各种与其他疾病相关的成功治疗靶标密切相互作用,如炎症、癌症和糖尿病,表明这些复杂疾病之间可能存在交叉对话。此外,细胞增殖和炎症上游的 Ca(2+)平衡维持途径被抗 AD 草药成分密集靶向,具有严格的统计评估。除了对 AD 发病机制的整体理解外,对草药成分作用机制的综合网络分析也可能为未来的疾病修饰策略提供新的线索。

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