Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders.
Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders.
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DOI：
10.3389/fphar.2017.00747
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发表时间：
2017
影响因子：
5.6
通讯作者：
Cheng F
中科院分区：
文献类型：
--
作者：
Fang J;Gao L;Ma H;Wu Q;Wu T;Wu J;Wang Q;Cheng F
衰老是指细胞和组织在一生中遗传和生理变化的积累，已显示出患各种复杂疾病的高风险，如神经退行性疾病、心血管疾病和癌症。在过去的几十年里，天然产品已经被证明是通过延长寿命和预防与衰老相关的疾病来抗衰老的干预者。在这项研究中，我们开发了一个集成的系统药理学基础设施，以揭示天然产品对衰老相关疾病的新适应症。具体地说，我们整合了411个高质量的与衰老相关的人类基因或来自小鼠(MM)、酿酒酵母(SC)、秀丽线虫(CE)和黑腹果蝇(DM)的人-直系物基因。我们通过整合实验和计算预测的药物-靶点相互作用(DTI)，构建了一个天然产物的全球药物-靶点网络。我们通过整合天然产物的抗衰老相关基因和药物靶标网络，进一步构建了天然产物抗衰老新适应症的统计网络模型。网络模型具有较高的精度。我们展示了四种典型天然产品(咖啡酸、二甲双胍、杨梅素和白藜芦醇)的几个网络预测的抗衰老适应症，并具有新的作用机制。总之，这项研究提供了一个强大的系统药理学基础设施，以确定用于治疗衰老相关疾病的天然产品。
Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders.
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