College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
J Orthop Surg Res. 2021 Oct 14;16(1):599. doi: 10.1186/s13018-021-02751-5.
Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology.
The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments.
According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density.
This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.
熟地黄能有效改善骨质疏松症的症状,但治疗骨质疏松症的分子机制尚不清楚。本研究旨在通过网络药理学探讨熟地黄治疗骨质疏松症的作用机制。
利用在线平台筛选熟地黄与骨质疏松症的重叠靶点。采用 Cytoscape 3.7.2 软件构建 PPI 的可视化网络图并进行分析。分子对接评估配体和受体的结合活性,并通过药理学实验验证一些关键基因。
根据拓扑分析结果,AKT1、MAPK1、ESR1 和 SRC 是熟地黄治疗骨质疏松症的关键基因,它们与豆甾醇和谷甾醇具有较高的结合活性。熟地黄治疗骨质疏松症的主要信号通路包括雌激素信号通路、HIF-1 信号通路、MAPK 信号通路和 PI3K-Akt 信号通路。动物实验结果表明,熟地黄能显著增加骨组织中 Akt1、MAPK1、ESR1 和 SRC1mRNA 的表达水平,从而增加骨密度。
本研究阐明了熟地黄治疗骨质疏松症的多成分、多靶点协同作用,为其临床应用和实验研究提供了新的思路。