目的 整合网络药理学、分子对接与斑马鱼模型实验，探讨桑寄生治疗糖尿病性骨质疏松症的潜在活性成分、核心靶点及作用机制。方法 通过文献挖掘结合TCMSP、ETCM、HERB、BATMAN-TCM数据库筛选桑寄生活性成分；利用SEA及SwissTargetPrediction数据库预测靶点。从GeneCards、OMIM等数据库获取糖尿病性骨质疏松症靶点，取交集后构建蛋白相互作用（PPI）网络并筛选核心靶点，进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析。采用AutoDock Vina进行分子对接验证。体外构建高糖诱导的MC3T3-E1细胞成骨分化抑制模型，通过碱性磷酸酶（ALP）活性及Western blotting检测桑寄生水提液对蛋白激酶B（Akt）通路影响。构建高糖诱导的斑马鱼骨形成抑制模型，桑寄生水提液干预后进行茜素红染色。结果 筛选出桑寄生活性成分98个，交集靶点95个，核心靶点包括胰岛素样生长因子1受体（IGF-1R）、Akt1等。KEGG富集显示靶点显著聚集于磷脂酰肌醇3-激酶（PI3K）/Akt等通路。分子对接表明槲皮素、苜蓿素等与IGF-1R结合良好。细胞实验显示，桑寄生水提液50 μg/mL组显著缓解高糖对ALP活性及p-Akt蛋白表达的抑制（P＜0.01），该效应可被Akt抑制剂MK2206部分逆转（P＜0.01）。斑马鱼实验发现，桑寄生水提液能恢复高糖抑制的头骨矿化面积（P＜0.01），且该作用可被IGF-1R抑制剂鬼臼苦素部分阻断（P＜0.05）。结论 桑寄生可能通过调控IGF-1R/Akt信号轴，缓解高糖所致的细胞成骨分化抑制和斑马鱼骨形成，发挥治疗糖尿病性骨质疏松症作用。

Objective To systematically investigate the potential active components, core targets, and underlying mechanisms of Taxilli herba in treatment of diabetic osteoporosis by integrating network pharmacology, molecular docking, and zebrafish model experiments. Methods Active components of Taxilli herba were screened through literature mining combined with TCMSP, ETCM, HERB, and BATMAN-TCM database. Potential targets were predicted using the SEA and SwissTargetPrediction databases. Diabetic osteoporosis-related targets were retrieved from GeneCards, OMIM, and other databases. Overlapping targets were identified to construct a PPI network, from which core targets were screened, followed by GO and KEGG enrichment analyses. Molecular docking validation was performed using AutoDock Vina. For in vitro verification, a high-glucose-induced osteogenic inhibition model was established in MC3T3-E1 cells. ALP activity and the Akt signaling pathway were assessed by ALP assay and Western blotting, respectively. A high-glucose-induced bone formation inhibition model was established in zebrafish. Taxilli herba intervention, bone mineralization was evaluated by alizarin red staining. Results A total of 98 active components and 95 overlapping targets were identified, with core targets including IGF-1R and Akt1. KEGG enrichment analysis revealed that targets were significantly enriched in the PI3K/Akt signaling pathway. Molecular docking demonstrated that quercetin, tricetin, and other key components exhibited favorable binding affinity with IGF-1R. In vitro experiments showed that Taxilli herba 50 μg/mL group were significantly alleviated the high-glucose-induced suppression of ALP activity and p-Akt protein expression (P < 0.01), and this effect was partially reversed by the Akt inhibitor MK2206 (P < 0.01). Zebrafish experiments confirmed that Taxilli herba restored high-glucose-suppressed cranial bone mineralization area (P < 0.01), and this osteoprotective effect was partially abolished by the IGF-1R inhibitor picropodophyllin (P < 0.05). Conclusion Taxilli herba may alleviate high glucose-induced inhibition of osteogenic differentiation and zebrafish bone formation by regulating the IGF-1R/Akt signaling axis, thereby exerting a therapeutic effect on diabetic osteoporosis.

R285.5

广东省基础与应用基础研究基金项目（2024A1515140131，2025A1515220124）；中华国际医学交流基金会内分泌代谢英才研究项目（2025-N-09-12）；“东莞名医”人才引进培养项目