加味独活寄生汤治疗骨质疏松症疗效机制的网络药理学研究
Network Pharmacological Study on Mechanism of the Therapeutic Effect of Modified Duhuo Jisheng Decoction in Osteoporosis.
作者信息
Huang Xudong, Zhou Zhou, Zheng Yingyi, Fan Guoshuai, Ni Baihe, Liu Meichen, Zhao Minghua, Zeng Lingfeng, Wang Weiguo
机构信息
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
School of Basic Medical Science, Zhejiang University of Traditional Chinese Medicine, Hangzhou, China.
出版信息
Front Endocrinol (Lausanne). 2022 Mar 31;13:860649. doi: 10.3389/fendo.2022.860649. eCollection 2022.
BACKGROUND
Modified Duhuo Jisheng Decoction (MDHJSD) is a traditional Chinese medicine prescription for the treatment of osteoporosis (OP), but its mechanism of action has not yet been clarified. This study aims to explore the mechanism of MDHJSD in OP through a combination of network pharmacology analysis and experimental verification.
METHODS
The active ingredients and corresponding targets of MDHJSD were acquired from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. OP-related targets were acquired from databases, including Genecards, OMIM, Drugbank, CTD, and PGKB. The key compounds, core targets, major biological processes, and signaling pathways of MDHJSD that improve OP were identified by constructing and analysing the relevant networks. The binding affinities between key compounds and core targets were verified using AutoDock Vina software. A rat model of ovariectomized OP was used for the experimental verification.
RESULTS
A total of 100 chemical constituents, 277 targets, and 4734 OP-related targets of MDHJSD were obtained. Subsequently, five core components and eight core targets were identified in the analysis. Pathway enrichment analysis revealed that overlapping targets were significantly enriched in the tumour necrosis factor-alpha (TNF-α) signaling pathway, an inflammation signaling pathway, which contained six of the eight core targets, including TNF-α, interleukin 6 (IL-6), transcription factor AP-1, mitogen-activated protein kinase 3, RAC-alpha serine/threonine-protein kinase, and caspase-3 (CASP3). Molecular docking analysis revealed close binding of the six core targets of the TNF signaling pathway to the core components. The results of experimental study show that MDHJSD can protect bone loss, inhibit the inflammatory response, and downregulate the expression levels of TNF-α, IL-6, and CASP3 in ovariectomized rats.
CONCLUSION
The mechanism of MDHJSD in the treatment of OP may be related to the regulation of the inflammatory response in the bone tissue.
背景
改良独活寄生汤（MDHJSD）是一种用于治疗骨质疏松症（OP）的中药方剂，但其作用机制尚未阐明。本研究旨在通过网络药理学分析与实验验证相结合的方法，探讨MDHJSD治疗OP的机制。
方法
从中药系统药理学（TCMSP）数据库中获取MDHJSD的活性成分及相应靶点。从Genecards、OMIM、Drugbank、CTD和PGKB等数据库中获取OP相关靶点。通过构建和分析相关网络，确定MDHJSD改善OP的关键化合物、核心靶点、主要生物学过程和信号通路。使用AutoDock Vina软件验证关键化合物与核心靶点之间的结合亲和力。采用去卵巢骨质疏松大鼠模型进行实验验证。
结果
共获得MDHJSD的100种化学成分、277个靶点和4734个OP相关靶点。随后，分析确定了5种核心成分和8个核心靶点。通路富集分析显示，重叠靶点在肿瘤坏死因子-α（TNF-α）信号通路（一种炎症信号通路）中显著富集，该通路包含8个核心靶点中的6个，包括TNF-α、白细胞介素6（IL-6）、转录因子AP-1、丝裂原活化蛋白激酶3、RAC-α丝氨酸/苏氨酸蛋白激酶和半胱天冬酶-3（CASP3）。分子对接分析显示TNF信号通路的6个核心靶点与核心成分紧密结合。实验研究结果表明，MDHJSD可保护去卵巢大鼠的骨质流失，抑制炎症反应，并下调TNF-α、IL-6和CASP3的表达水平。
结论
MDHJSD治疗OP的机制可能与调节骨组织中的炎症反应有关。
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