Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Research Center for Special Medicine and Health Systems Engineering, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Research Center for Special Medicine and Health Systems Engineering, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Science, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
Life Sci. 2019 Oct 15;235:116820. doi: 10.1016/j.lfs.2019.116820. Epub 2019 Aug 30.
Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone mass decrease and microstructural degradation, which may increase the risk of bone fracture and leading to high morbidity. Dipsaci Radix (DR), one typical traditional Chinese medicine (TCM), which has been applied in the treatment of OP with good therapeutic effects and few side effects. However, the underlying molecular mechanisms of DR to treat OP have not been fully elucidated. In this study, we aim to dissect the molecular mechanism of DR in the treatment of OP.
A systems pharmacology approach was employed to comprehensively dissect the action mechanisms of DR for the treatment of OP.
10 compounds were screened out as the potential active ingredients with excellent biological activity based on in silico ADME (absorption, distribution, metabolism and excretion) prediction model. Then, 36 key protein targets of 6 compounds were identified by systems drug targeting model (SysDT) and they were involved in several biological processes, such as osteoclast differentiation, osteoblast differentiation and anti-inflammation. The target-pathway network indicated that targets are mainly mapped in multiple signaling pathways, i.e., MAPK, Tumor necrosis factor α (TNF-α), NF-κb and Toll-like receptor pathways. The in vitro results indicated that the compounds ursolic acid and beta-sitosterol effectively inhibited the osteoclast differentiation.
These results systematically dissected that DR exhibits the therapeutic effects of OP by the regulation of immune system-related pathways, which provide novel perspective to drug development of OP.
骨质疏松症（OP）是一种以骨量减少和微观结构退化为特征的系统性代谢性骨病，可能会增加骨折风险，导致高发病率。续断（DR）是一种典型的中药，已被应用于治疗 OP，具有良好的治疗效果和较少的副作用。然而，DR 治疗 OP 的潜在分子机制尚未完全阐明。在这项研究中，我们旨在剖析 DR 治疗 OP 的分子机制。
采用系统药理学方法全面剖析 DR 治疗 OP 的作用机制。
基于计算机 ADME（吸收、分布、代谢和排泄）预测模型，筛选出 10 种具有良好生物活性的潜在活性成分。然后，通过系统药物靶标模型（SysDT）鉴定出 6 种化合物的 36 个关键蛋白靶标，它们涉及多个生物学过程，如破骨细胞分化、成骨细胞分化和抗炎。靶标-通路网络表明，靶标主要映射在多个信号通路中，如 MAPK、肿瘤坏死因子-α（TNF-α）、NF-κb 和 Toll 样受体通路。体外结果表明，化合物熊果酸和β-谷甾醇能有效抑制破骨细胞分化。
这些结果系统地剖析了 DR 通过调节免疫系统相关途径发挥治疗 OP 的作用，为 OP 的药物开发提供了新的视角。
