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| 基于网络药理学与实验探讨山萘酚抗骨质疏松作用 |
| Exploration of the anti-osteoporotic effects of kaempferol based on network pharmacology and experimental study |
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| DOI：10.3969/j.issn.1006-7108.2026.06.016 |
| 中文关键词: 骨质疏松症 山萘酚 自噬 网络药理学 |
| 英文关键词:osteoporosis kaempferol autophagy network pharmacology |
| 基金项目:广东省中医药局科研项目（20251333）；深圳市科技创新委员会研究项目（JCYJ20240813103617024, JCYJ20250604185304006）；深圳市宝安区科创局科研项目（2024JD305）；深圳市宝安区中医药协会临床研究专项(2023ZYYLCZX-2)；深圳市医疗卫生三名工程资助项目（SZZYSM20231101017） |
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| 中文摘要: |
| 目的 基于网络药理学及体外实验探讨山萘酚（kaempferol，Kae）在骨质疏松症（osteoporosis, OP）治疗中的作用。方法 结合网络药理学、分子对接及体外实验。通过SwissTargetPrediction和GEO数据库筛选Kae作用靶点及OP相关差异基因，利用STRING和Cytoscape构建蛋白互作网络，并通过基因本体论（gene ontology, GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析确定关键通路。采用分子对接验证Kae与靶点的结合能力，并通过MC3T3-E1细胞实验评估Kae对成骨分化、矿化及自噬的影响，检测PI3K/AKT/mTOR通路蛋白表达。结果 筛选出14个Kae抗OP潜在靶点，核心基因为AKT1、PIK3R1和ESR1。分子对接显示Kae与靶点结合良好（结合能≤– 5 kcal/mol）。体外实验表明，50 μmol/L Kae显著促进MC3T3-E1细胞增殖、ALP活性及钙沉积（P<0.05），上调自噬标志蛋白LC3-II/LC3-I比值，降低p62水平，并抑制PI3K/AKT/mTOR通路磷酸化。结论 Kae通过抑制PI3K/AKT/mTOR信号通路激活自噬，促进成骨细胞分化与矿化，为OP治疗提供了潜在分子机制及实验依据。 |
| 英文摘要: |
| Objective To investigate the role of kaempferol (Kae) in the treatment of osteoporosis (OP) using network pharmacology and in vitro experiments. Methods Network pharmacology, molecular docking, and in vitro experiments were integrated. Potential targets of Kae and OP-related differentially expressed genes (DEGs) were screened using SwissTargetPrediction and GEO databases. Protein-protein interaction (PPI) networks were constructed via STRING and Cytoscape, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was used to validate the Kae-target binding affinity. MC3T3-E1 cells were used to assess the effect of Kae on osteogenic differentiation, mineralization, and autophagy. Expressions of proteins in PI3K/AKT/mTOR signaling pathway were examined. Results Fourteen anti-OP targets were identified, with AKT1, PIK3R1, and ESR1 as hub genes. Molecular docking confirmed strong binding between Kae and targets (binding energy ≤– 5 kcal/mol). In vitro, 50 μmol/L of Kae enhanced MC3T3-E1 cell proliferation, ALP activity, and calcium deposition (P<0.05), upregulated LC3-II/LC3-I ratio, reduced p62 levels, and suppressed PI3K/AKT/mTOR pathway phosphorylation. Conclusion Kae activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby promoting osteoblast differentiation and mineralization, offering a novel therapeutic strategy for OP. |
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