目的 通过网络药理学、分子对接技术探讨党参治疗糖尿病性骨质疏松症（DOP）的作用机制。方法 通过 文献检索和中药系统药理学数据库和分析平台（TCMSP）检索获得党参的活性成分和对应靶点；利用 GeneCards、OMIM 数据库筛选 DOP 相关靶点，并取党参活性成分靶点与 DOP 相关靶点的交集靶点。通过 STRING 数据库和 Cytoscape 3.8.0 软件分别构建蛋白质-蛋白质相互作用（PPI）网络和“党参-成分-靶点”网络 图，并筛选出党参治疗 DOP 的核心靶点和核心成分。利用 DAVID 数据库对交集靶点进行基因本体（GO）功能 和京都基因与基因组百科全书（KEGG）通路富集分析，并采用分子对接技术评估党参治疗 DOP 核心靶点和核心 成分的结合活性。结果 共筛选出 39 个党参相关活性成分，610 个作用靶点；GeneCards 数据库和 OMIM 数据库共获得 1 715 个 DOP 相关靶点，取二者的交集得到党参治疗 DOP 的潜在靶点 210 个。党参治疗 DOP 的 核心靶点有非受体酪氨酸激酶（SRC）、信号转导和转录激活因子 3（STAT3）、磷酸肌醇-3-激酶催化亚基 α （PIK3CA）、磷脂酰肌醇 3-激酶调节亚基 1（PIK3R1）、热休克蛋白 90α 家族 A 类成员 1（HSP90AA1），核心成分 有 7-甲氧基-2-甲基异黄酮、木犀草素、芹菜素、9，10-二羟基-12-十八碳烯酸、11-羟基兰金断肠草碱。 KEGG 通路富集分析得到党参治疗 DOP 的作用机制与磷脂酰肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）、缺氧诱导因子 1 （HIF-1）和糖尿病并发症中的 AGE-RAGE 信号通路等信号通路有关。分子对接结果显示，党参的 5 种核心活性 成分（7-甲氧基-2-甲基异黄酮、木犀草素、芹菜素、9，10-二羟基-12-十八碳烯酸、11-羟基兰金断肠草碱）与 SRC、STAT3、PIK3CA、PIK3R1 等核心靶点的结合活性较好（均＜-5 kcal·mol-1 ）。结论 党参治疗 DOP 具有多成 分、多靶点、多通路特点，其治疗作用机制可能与 PI3K/Akt、HIF-1 和糖尿病并发症中的 AGE-RAGE 信号通 路等信号通路有关。

Objective To investigate the mechanism of Codonopsis Radix in treating diabetic osteoporosis （DOP） using network pharmacology and molecular docking technology. Methods The active components of Codonopsis Radix and their corresponding targets were obtained through literature retrieval and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to DOP were screened using the GeneCards and OMIM databases. The intersection targets between the active component targets of Codonopsis Radix and DOPrelated targets were identified. A protein-protein interaction （PPI） network and a “Codonopsis Radix-componenttarget” network diagram were constructed using the STRING database and Cytoscape 3.8.0 software，respectively，to screen out the core targets and active components of Codonopsis Radix for DOP treatment. The DAVID database was used for Gene Ontology （GO） functional and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses of the intersection targets. Molecular docking technology was employed to evaluate the binding activity between the core targets for DOP treatment and the core active components of Codonopsis Radix. Results A total of 39 active components related to Codonopsis Radix and 610 corresponding targets were screened. The GeneCards and OMIM databases yielded 1 715 DOP-related targets. The intersection of these two sets identified 210 potential targets for Codonopsis Radix in treating DOP. The core targets for Codonopsis Radix in treating DOP included non-receptor tyrosine kinase （SRC）， signal transducer and activator of transcription 3（STAT3），phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA）， phosphinositide-3-kinase regulatory subunit 1（PIK3R1）， and heat shock protein 90α family class A member 1 （HSP90AA1）. The core active components included 7-methoxy-2-methyl isoflavone， luteolin，apigenin，9，10-dihydroxy-12-octadecenoic acid，and 11-hydroxyrankinidine. KEGG pathway enrichment analysis revealed that the mechanisms of Codonopsis Radix in treating DOP are related to signaling pathways such as the PI3K/Akt， HIF-1， and AGE-RAGE signaling pathways in diabetic complications. Molecular docking demonstrated that the five core active components of Codonopsis Radix （7-methoxy-2-methyl isoflavone，luteolin，apigenin，9，10- dihydroxy-12-octadecenoic acid，and 11-hydroxyrankinidine） exhibited favorable binding activities （all < -5 kcal·mol-1 ） with core targets like SRC，STAT3，PIK3CA，and PIK3R1. Conclusion Codonopsis Radix exerts therapeutic effects on diabetic osteoporosis through multiple components，targets，and pathways. Its mechanism of action may be associated with signaling pathways such as PI3K/Akt，HIF-1，and the AGE-RAGE signaling pathway in diabetic complications.

R285.5

广东省医学科研基金项目（A2024138，B2025580）；广东省医院药学研究基金项目（2025A01002）。