Network Pharmacological Analysis and Animal Experimental Study on Osteoporosis Treatment with GuBen-ZengGu Granules.
Network Pharmacological Analysis and Animal Experimental Study on Osteoporosis Treatment with GuBen-ZengGu Granules.
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DOI：
10.1155/2023/9317557
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发表时间：
2023
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影响因子：
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采用网络药理学和动物实验相结合的方法，探讨固本增骨颗粒治疗骨质疏松症的分子途径和物质基础。 从中药信息库和BATMAN-TCM数据库中检索出中药固本固本颗粒的有效活性成分和潜在作用靶点。从GeneCard、NCBI和DisGeNET获得疾病相关基因。接着，使用STRING数据库建立蛋白质相互作用网络，并使用MCODE模块筛选核心基因。采用Cytoscape 3.8.0软件构建组分-疾病-通路-靶点网络，利用clusterProfiler R软件包进行KEGG通路富集分析，预测固骨固骨颗粒治疗骨质疏松症的作用机制。采用卵巢切除术（OVX）建立骨质疏松大鼠模型，并对网络药理学的部分结果进行了实验验证。 药效学结果显示，骨固颗粒能显著提高模型大鼠的骨密度，改善股骨的微观结构指标。网络药理学研究结果显示，槲皮素、毛地黄黄酮、豆甾醇、当归素、山奈酚、补骨脂素、补骨脂素、7-O-甲基异小核甘酸、异鼠李素、芒柄花素、β-谷甾醇是GBZGG的主要成分，而MAPK 1、AKT 1、JUN、HSP 90 AA 1、RELA、MAPK 14、ESR 1、RXRA、FOS、MAPK 8、NCOA 1、MYC、IL-6是其治疗骨质疏松的核心靶点。其生物学效应可能是通过调节流体切应力信号通路和动脉粥样硬化、晚期糖基化终产物等信号通路来实现的糖尿病并发症、前列腺癌、白细胞介素（IL-17）、肿瘤坏死因子（TNF）、B型肝炎、丝裂原活化蛋白激酶（MAPK）、动物实验结果表明，骨固颗粒能降低血清IL-6、TNF-α水平，增加骨形态发生蛋白-2（BMP-2）、侏儒相关转录因子2（RUNX 2）蛋白表达，抑制细胞外调节蛋白激酶（ERK 1/2）和磷酸化ERK 1/2（p-ERK 1/2）蛋白的活性。 GBZGG通过抑制IL-6和TNF-α的作用降低ERK 1/2和p-ERK 1/2蛋白和mRNA的表达，并负性调节MAPK/ERK信号通路。骨质疏松模型表明，该方能有效改善大鼠骨量丢失和骨微结构破坏，维持骨代谢正平衡。
We explored the molecular pathway and material basis of GuBen-ZengGu granules (GBZGG) in treating osteoporosis using network pharmacology and animal experiments. The effective active components and potential targets of GBZGG were obtained from the TCMSP database and BATMAN-TCM database. Disease-related genes were obtained from GeneCard, NCBI, and DisGeNET. Next, a protein interaction network was established using the STRING database, and core genes were screened using the MCODE module. Cytoscape 3.8.0 was used to construct the network of component-disease-pathway-target, and KEGG pathway enrichment analyses were performed using the clusterProfiler R package to predict the mechanism of GBZGG in treating osteoporosis. An osteoporosis rat model was established by ovarian excision (OVX), and the partial results of network pharmacology were experimentally verified. Pharmacodynamic results showed that GBZGG increased bone mineral density (BMD) and significantly improved the indexes of femur microstructure in model rats. The network pharmacology results showed that quercetin, luteolin, stigmasterol, angelicin, kaempferol, bakuchiol, bakuchiol, 7-O-methylisomucronulatum, isorhamnetin, formononetin, and beta-sitosterol are the major components of GBZGG, with MAPK1, AKT1, JUN, HSP90AA1, RELA, MAPK14, ESR1, RXRA, FOS, MAPK8, NCOA1, MYC, and IL-6 as its core targets for treating osteoporosis. Biological effects could be exerted by regulating the signaling pathways of fluid shear stress and the signaling pathways of atherosclerosis, advanced glycation end products (AGE-RAGE) of diabetic complications, prostate cancer, interleukin (IL-17), tumor necrosis factor (TNF), hepatitis B, mitogen-activated protein kinase (MAPK), etc. The results of animal experiments showed that GBZGG could reduce the serum levels of IL-6 and TNF-α, increase the expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2) protein, and inhibit the activity of extracellular-regulated protein kinases (ERK1/2) and phosphorylation ERK1/2 (p-ERK1/2) protein. GBZGG reduces the expression of ERK1/2 and p-ERK1/2 proteins and mRNAs through the inhibitory effects on IL-6 and TNF-α and negatively regulates the MAPK/ERK signaling pathway. The osteoporosis model showed that it effectively improved the loss of bone mass and destruction of bone microstructure in rats and maintained a positive balance for bone metabolism.
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影响因子：
5.6
作者：
Kim, Tae-Ho;Jung, Ji Won;Kim, Shin-Yoon
通讯作者：
Kim, Shin-Yoon
影响因子：
5.6
作者：
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影响因子：
3.1
作者：
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影响因子：
4.4
作者：
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通讯作者：
Trivedi, Ritu
影响因子：
2
作者：
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通讯作者：
Lee, Kwang Youl