Department of Pharmacy, Shengzhou People's Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, China.
Department of Orthopedic Surgery, the Third People's Medical and Health Group of Cixi City, Ningbo, China.
Medicine (Baltimore). 2022 May 13;101(19):e29257. doi: 10.1097/MD.0000000000029257.
Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein-protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.
绝经后骨质疏松症（PMOP）已成为全球最常见的慢性疾病之一，随着人口老龄化，PMOP 患者日益增多。杜仲（EU）是一种传统中药，长期以来一直用于治疗 PMOP。本研究旨在通过网络药理学方法探讨 EU 治疗 PMOP 的药理机制。从中药系统药理学数据库中获取 EU 的活性成分，并在 UniProt 数据库中对这些成分进行靶标预测，以鉴定其相对靶标。然后，我们使用 GeneCards 数据库和 DisGeNET 数据库筛选 PMOP 的靶标。获得 PMOP 和 EU 之间的重叠基因，进行蛋白质-蛋白质相互作用、基因本体分析、京都基因与基因组百科全书分析。从 EU 中鉴定出 28 种活性成分，对应 207 个靶标。此外，与 PMOP 密切相关的靶标有 292 个，其中 50 个与 EU 的靶标相匹配，被认为具有治疗相关性。基因本体富集分析表明，EU 通过调节细胞增殖、血管生成和炎症反应等多种生物学过程发挥抗 PMOP 作用。京都基因与基因组百科全书富集分析揭示了几个可能参与调节上述生物学过程的途径，如 PI3K-AKT 途径、丝裂原活化蛋白激酶途径、缺氧诱导因子-1 途径、肿瘤坏死因子途径和白细胞介素-17 途径。通过网络药理学方法，我们系统地研究了 EU 治疗 PMOP 的机制。本研究中鉴定的多靶点和多途径为进一步确定 EU 的更确切机制提供了新的思路。
