Network Pharmacology-Based Strategy for the Investigation of the Anti-Obesity Effects of an Ethanolic Extract of Zanthoxylum bungeanum Maxim.

Network Pharmacology-Based Strategy for the Investigation of the Anti-Obesity Effects of an Ethanolic Extract of Zanthoxylum bungeanum Maxim.
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基于网络药理学的策略研究花椒乙醇提取物的抗肥胖作用

DOI:
10.3389/fphar.2020.572387
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发表时间:
2020
影响因子:
5.6
通讯作者:
Su T
Su T
中科院分区:
医学2区
文献类型:
--
作者:
Wang Y;Yang SH;Zhong K;Jiang T;Zhang M;Kwan HY;Su T

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网络药理学被认为是药物发现的下一个范式。在肥胖已成为全球流行病的时代,网络药理学成为发现具有有效抗肥胖效果的新型草药疗法的理想工具。花椒是一种中草药。成熟的ZBM果皮用于疾病治疗和烹饪的香料。在这里,我们使用网络药理学的方法来研究ZBM是否具有减肥作用,并揭示其潜在的作用机制。我们首先构建了ZBM相关肥胖靶标的药物-成分-基因标志-疾病网络和蛋白质-蛋白质相互作用网络,然后进行了基因本体学和京都百科全书的基因和基因组路径浓缩分析。这些结果表明,细胞凋亡是一条有希望的信号通路,介导了ZBM的减肥作用。分子对接还揭示了Qercetin,ZBM中的一种化合物,在化合物-靶点网络中具有最高程度的连接,并与凋亡标记物直接结合。此外,在3T3-L1脂肪细胞和高脂饮食诱导的肥胖小鼠模型中,ZBM的凋亡作用进一步得到验证。这些发现不仅表明ZBM可以被开发为潜在的减肥疗法,而且也证明了网络药理学在发现以草药为基础的疗法用于疾病治疗方面的应用。
Network pharmacology is considered as the next paradigm in drug discovery. In an era when obesity has become global epidemic, network pharmacology becomes an ideal tool to discover novel herbal-based therapeutics with effective anti-obesity effects. Zanthoxylum bungeanum Maxim (ZBM) is a medicinal herb. The mature pericarp of ZBM is used for disease treatments and as spice for cooking. Here, we used the network pharmacology approach to investigate whether ZBM possesses anti-obesity effects and reveal the underlying mechanism of action. We first built up drug–ingredient–gene symbol–disease network and protein–protein interaction network of the ZBM-related obesity targets, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The results highlight apoptosis as a promising signaling pathway that mediates the anti-obesity effects of ZBM. Molecular docking also reveals quercetin, a compound in ZBM has the highest degree of connections in the compound-target network and has direct bindings with the apoptotic markers. Furthermore, the apoptotic effects of ZBM are further validated in 3T3-L1 adipocytes and in the high-fat diet–induced obesity mouse model. These findings not only suggest ZBM can be developed as potential anti-obesity therapeutics but also demonstrate the application of network pharmacology for the discovery of herbal-based therapeutics for disease treatments.
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