中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (11): 2702-2711.doi: 10.12307/2026.095

• 骨组织构建 bone tissue construction • 上一篇    下一篇

菟丝子活性成分苦参碱治疗绝经后骨质疏松症：网络药理学分析及实验验证

徐  晟1，2，张稳稳3，张薇薇1，2，王宏涛1，2，张  军2，杨瑞盛2，原  媛4，王  丽4，5，郝海虎1，2   

  1. 1山西中医药大学第一临床学院，山西省晋中市   030600；2山西医科大学第三医院山西白求恩医院山西医学科学院骨科，山西省太原市   030000；3新疆和田学院中医学院，新疆维吾尔自治区和田市   848000；山西医科大学，4基础医学研究中心，5基础医学院病理教研室，山西省晋中市   030600
  • 收稿日期:2025-02-20 接受日期:2025-06-13 出版日期:2026-04-18 发布日期:2025-09-02
  • 通讯作者: 郝海虎，博士，主任医师，山西中医药大学第一临床学院，山西省晋中市 030600；山西医科大学第三医院山西白求恩医院山西医学科学院骨科，山西省太原市 030000
  • 作者简介:徐晟，男，1998年生，浙江省金华市人，汉族，山西中医药大学在读硕士，主要从事中医药防治脊柱退行性变的研究。
  • 基金资助:
    山西省中医药管理局科研项目(2024ZYY2A020)，项目负责人：郝海虎

Network pharmacological analysis and experimental verification of semen cuscutae in treating postmenopausal osteoporosis

Xu Sheng1, 2, Zhang Wenwen3, Zhang Weiwei1, 2, Wang Hongtao1, 2, Zhang Jun2, Yang Ruisheng2, Yuan Yuan4, Wang Li4, 5, Hao Haihu1, 2   

  1. 1First Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030600, Shanxi Province, China; 2Department of Orthopedics, Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China; 3School of Traditional Chinese Medicine, Xinjiang Hetian College, Hetian 848000, Xinjiang Uygur Autonomous Region, China; 4Basic Medical Research Center, 5Department of Pathology, School of Basic Medicine, Shanxi Medical University, Jinzhong 030600, Shanxi Province, China
  • Received:2025-02-20 Accepted:2025-06-13 Online:2026-04-18 Published:2025-09-02
  • Contact: Hao Haihu, MD, Chief physician, First Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030600, Shanxi Province, China; Department of Orthopedics, Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
  • About author:Xu Sheng, MS candidate, First Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030600, Shanxi Province, China; Department of Orthopedics, Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
  • Supported by:
    Scientific Research Project of Shanxi Provincial Administration of Traditional Chinese Medicine, No. 2024ZYY2A020 (to HHH)

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摘要：


文题释义：
网络药理学：是一种结合了药理学和系统生物学的方法，通过研究药物的分子结构和特性，并结合疾病的相关基因，共同构建药物-成分-靶点-疾病的可视化网络，有助于识别药物中的关键活性成分，发现可能的作用靶点，用于预测中医药治疗效果的可能机制，从而为药物研发和疾病治疗提供新的视角和方法。
绝经后骨质疏松症：主要发生于女性绝经后的5-10年内，因卵巢功能衰退、雌激素水平显著下降，导致骨代谢失衡，骨吸收超过骨形成，从而引起以骨量减少、骨脆性增加及易于骨折为特征的代谢性骨骼疾病。

背景：传统中药材菟丝子是妇科常用药且不良反应相对较小，逐渐展现出抗绝经后骨质疏松症的潜力，为这一疾病的治疗提供了新的思路和可能。
目的：基于网络药理学分析和分子对接探究菟丝子抗绝经后骨质疏松症的作用机制，并结合动物实验验证。
方法：在TCMSP数据库中筛选菟丝子的主要活性成分和对应靶点，在GeneCards、OMIM、PharmGKB数据库中收集绝经后骨质疏松症的疾病靶点；取共同作用靶点后进行一系列分析，筛选出核心靶点；通过GO功能分析核心靶点并通过分子对接验证核心靶点的作用，选择对应的活性成分进行动物实验验证。
结果与结论：①筛选出菟丝子主要活性成分共11个，菟丝子和绝经后骨质疏松症的共同作用靶点共110个，筛选出10个核心靶点；②GO功能分析表明核心靶点与氧化应激以及雌激素密切相关；③将排名前2位的核心靶点蛋白白细胞介素6、活化T细胞核因子1进行分子对接，选择亲和力排名前2位的苦参碱和白细胞介素6、苦参碱和活化T细胞核因子1进行动物实验验证；④动物实验显示苦参碱能抑制白细胞介素6和活化T细胞核因子1水平，改善绝经后骨质疏松症大鼠的骨小梁结构。结果表明：低剂量苦参碱通过下调白细胞介素6水平，影响白细胞介素6/可溶性白细胞介素6受体系统的平衡状态，与核因子κB、丝裂原活化蛋白激酶信号通路共同抑制下游活化T细胞核因子1的表达，从而抑制破骨细胞分化，减少骨吸收，治疗绝经后骨质疏松症。
https://orcid.org/0009-0000-9202-7072(徐晟)；https://orcid.org/0000-0002-7225-1349 (郝海虎)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 菟丝子, 绝经后骨质疏松症, 网络药理学, 分子对接, 苦参碱, 白细胞介素6, 活化T细胞核因子1

Abstract: BACKGROUND: Semen cuscutae, a traditional Chinese medicine, has gradually shown its potential in anti-postmenopausal osteoporosis because of its relatively small side effects, which provides new ideas and possibilities for the treatment of this disease.
OBJECTIVE: To explore the mechanism of anti-postmenopausal osteoporosis of semen cuscutae based on network pharmacological analysis and molecular docking and to validate it with animal experiments. 
METHODS: The main active components and corresponding targets of semen cuscutae were screened in TCMSP database, and the disease targets of postmenopausal osteoporosis were collected in GeneCards, OMIM and PharmGKB databases. After identification of common targets, a series of analyses were carried out, and core targets were selected. The core targets were analyzed by GO function and their role was verified by molecular docking. The corresponding active components were selected for animal experiments.
RESULTS AND CONCLUSION: (1) Eleven main active components of semen cuscutae and 110 common targets of semen cuscutae and postmenopausal osteoporosis were screened out, and 10 core targets were identified. (2) GO function analysis showed that the core targets were closely related to oxidative stress and estrogen. (3) The top two ranked core target proteins, interleukin-6 and activated T-cell nuclear factor 1, were molecularly docked, and the top two ranked affinities, picloram and interleukin-6 as well as picloram and activated T-cell nuclear factor 1, were selected for validation in animal experiments. (4) Animal experimental results showed that matrine could inhibit the levels of interleukin-6 and activated T-cell nuclear factor 1 and improve trabecular bone structure of rats with postmenopausal osteoporosis. To conclude, low-dose matrine may affect the steady state of interleukin-6/soluble interleukin-6 receptor system by decreasing the level of interleukin-6, and inhibit the expression of nuclear factor 1 in downstream transcription factor-activated T cells in combination with nuclear factor-κB and mitogen-activated protein kinase signaling pathway to inhibit osteoclast differentiation, reduce bone resorption, repair trabecular structure and treat postmenopausal osteoporosis.


Key words: semen cuscutae, postmenopausal osteoporosis, network pharmacology, molecular docking, matrine, interleukin-6, activated T cell nuclear factor 1

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