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下调炎症因子的抗骨质疏松作用:一项网络药理学及去卵巢大鼠模型研究

The Anti-Osteoporosis Effects of Downregulation of Inflammatory Factors: A Network Pharmacology and Ovariectomized Rat Model Study.

作者信息

Zhang Yumiao, Liu Yang, Zhang Yuchen, Shi Xinbo, Li Yingang, Pan Yalei

机构信息

Shaanxi University of Chinese Medicine, Xianyang 712046, China.

Xidian Group Hospital, Xi'an, 710032, China.

出版信息

Endocr Metab Immune Disord Drug Targets. 2025 Jun 20. doi: 10.2174/0118715303371787250609162705.

DOI:10.2174/0118715303371787250609162705
PMID:40574401
Abstract

OBJECTIVE

Osteoporosis is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. has been clinically used in the treatment of bone diseases, especially osteoporosis. However, there is a lack of study on the mechanism of osteoporosis treatment with .

MATERIALS AND METHODS

A network pharmacology approach was employed to identify the targets of osteoporosis and . Cytoscape 3.7.2 and DAVID were used to visualize the pharmacological mechanism of in treating osteoporosis by building up compound-target and protein-protein interaction (PPI) networks and conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. An ovariectomized SD rat osteoporosis model was used to assess the potential therapeutic effect of in vivo. The biomechanical properties, pathological changes, inflammatory cytokines, bone density, and bone microstructural parameters in rat bone tissue were carefully measured. The biochemical markers of bone metabolism in serum were detected by Enzyme-Linked Immunosorbent Assay (ELISA).

RESULTS

Fifty-two active components and sixty-five target genes of involved in the treatment of osteoporosis were identified. The PPI network revealed IL-6, TNF, NR3C1, IL-1β, CASP3, ESR1, PGR, and AR to be involved in the treatment of osteoporosis with . Chikusetsusaponin IVa and Radix ginsenoside-Ro were the main saponins found in . was found to exert potent preventive effects on osteoporosis by maintaining biomechanical properties, increasing bone mineral density, and protecting the trabecular microstructure in an ovariectomized rat osteoporosis model. hindered the initiation of osteoporosis induced by ovariectomy by regulating bone metabolism and downregulating the expression of IL-6 and TNF-α.

CONCLUSION

was found to contain 52 compounds and 65 targets in the treatment of osteoporosis. The administration of could mitigate osteoporosis in rats induced by ovariectomy, and one of the mechanisms was associated with downregulating the expression of inflammatory factors.

摘要

目的

骨质疏松症是一个日益严重的主要公共卫生问题,其特征是骨矿物质密度降低和骨微结构破坏。[药物名称]已在临床上用于治疗骨疾病,尤其是骨质疏松症。然而,关于[药物名称]治疗骨质疏松症的机制缺乏研究。

材料与方法

采用网络药理学方法确定骨质疏松症和[药物名称]的靶点。利用Cytoscape 3.7.2和DAVID,通过构建化合物-靶点和蛋白质-蛋白质相互作用(PPI)网络,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,以可视化[药物名称]治疗骨质疏松症的药理机制。使用去卵巢SD大鼠骨质疏松模型评估[药物名称]在体内的潜在治疗效果。仔细测量大鼠骨组织的生物力学性能、病理变化、炎性细胞因子、骨密度和骨微结构参数。通过酶联免疫吸附测定(ELISA)检测血清中骨代谢的生化标志物。

结果

确定了[药物名称]治疗骨质疏松症涉及的52种活性成分和65个靶基因。PPI网络显示白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、核受体亚家族3成员C1(NR3C1)、白细胞介素-1β(IL-1β)、半胱天冬酶3(CASP3)、雌激素受体1(ESR1)、孕激素受体(PGR)和雄激素受体(AR)参与[药物名称]治疗骨质疏松症。竹节人参皂苷IVa和人参皂苷-Ro是在[药物名称]中发现的主要皂苷。在去卵巢大鼠骨质疏松模型中,[药物名称]被发现通过维持生物力学性能、增加骨矿物质密度和保护小梁微结构,对骨质疏松症具有显著的预防作用。[药物名称]通过调节骨代谢和下调IL-6和TNF-α的表达,阻碍了去卵巢诱导的骨质疏松症的发生。

结论

发现[药物名称]在治疗骨质疏松症中含有52种化合物和65个靶点。给予[药物名称]可减轻去卵巢诱导的大鼠骨质疏松症,其机制之一与下调炎性因子的表达有关。

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