基于网络药理学和分子对接探讨续断治疗骨质疏松性骨折作用机制
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Discussion on Action Mechanism of Dipsaci Radix for Osteoporotic Fracture Based on Network Pharmacology and Molecular Docking
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    摘要:

    目的:运用网络药理学及分子对接技术探讨续断治疗骨质疏松性骨折(OPF) 的作用机制。方 法:采用中药系统药理学数据库与分析平台(TCMSP) 筛选续断具有高活性的潜在有效成分,通过GeneCards 和OMIM 数据库筛选OPF 的相关靶标,运用Metascape 数据库对OPF 相关靶标进行映射,确定续断对OPF 的 可能靶标。利用Cytoscape 软件搭建续断治疗OPF 的药物-成分-疾病-靶点网络;通过STRING 平台构建蛋白 质互作网络;利用David 数据库提供的续断相关靶标进行基因本体论(GO) 和京都基因和基因组百科全 书(KEGG) 通路富集分析;最后通过分子对接验证核心靶点和续断活性成分的结合能力。结果:续断治疗 OPF 的主要活性成分主要有龙胆碱(Gentisin)、β-谷甾醇(β-sitosterol)、谷甾醇(Sitosterol)、(E,E)-3,5-二 邻咖啡酰奎宁酸([ E,E)-3,5-Di-O-caffeoylquinic acid]和林生续断苷Ⅲ-qt(SylvestrosideⅢ-qt)等成分,其作用 于半胱氨酸天冬氨酸蛋白酶3(CASP3)、β2-肾上腺素受体基因(ADRB2)、Bcl-2 相关X 蛋白(BAX)、B 淋巴 细胞瘤-2 基因(BCL2)、半胱氨酸天冬氨酸蛋白酶8(CASP8)、雌激素受体2(ESR2)、半胱氨酸天冬氨酸蛋 白酶9(CASP9)、二肽基肽酶-4(DPP4)、糖原合成酶激酶3(GSK3β)、异常凝血酶原(F2) 等靶点。续断 能够通过参与转录调控和细胞凋亡执行阶段的半胱氨酸型内肽酶、G 蛋白偶联胺受体、缩氨酸酶活性等生物过 程,调控癌症通路、弓形体病、卡波西肉瘤相关的疱疹病毒感染、乙型肝炎、大肠癌、小细胞肺癌脂质与动脉 粥样硬化、雌激素信号通路来发挥治疗OPF 的作用。分子对接结果显示,续断的活性成分(E,E) -3,5-二邻 咖啡酰奎宁酸、龙胆碱、威岩仙皂苷A_qt、β-谷甾醇与CASP3、ADRB2、CASP8 有较好的亲和力。结论:续 断可通过直接作用骨代谢相关途径和参与调节上下游多个信号通路对OPF 进行治疗,CASP3 及癌症通路可能 是其治疗OPF 的关键靶点及通路。

    Abstract:

    Abstract:Objective:To explore the action mechanism of Dipsaci Radix for osteoporotic fracture (OPF) based on network pharmacology and molecular docking. Methods: The potential active components of Radix Dipsaci with high activity were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP); the related targets of OPF were screened by GeneCards and OMIM database;the potential targets of Dipsaci Radix against OPF were identified by phase mapping of the related targets of OPF by Metascape database. The "medicines- compositions- diseases- targets" network of Dipsaci Radix for OPF was constructed by Cytoscape software;the protein-protein interaction network was constructed by STRING platform; the genetic ontological (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by the Dipsaci Radix- related targets provided by the David database. Finally, the binding ability of the core targets and the active ingredients of Dipsaci Radix was verified by molecular docking. Results: The main active ingredients of Dipsaci Radix for OPF mainly include Gentisin,β-sitosterol,Sitosterol,(E,E)-3,5-Di-O-caffeoylquinic acid and Sylvestroside Ⅲ- qt, which act on caspase 3 (CASP3), β2- adrenergic receptor gene (ADRB2), Bcl- 2 associated X protein (BAX), B lymphocytoma- 2 gene (BCL2), caspase 8 (CASP8), estrogen receptor 2 (ESR2),caspase 9 (CASP9),dipeptidyl peptidase-4 (DPP4),glycogen synthase kinase 3 (GSK3β), abnormal prothrombin (F2) and other targets. By participating in biological processes such as cysteine endopeptidase, G protein- coupled amine receptor, and peptidase activity in the executive phase of transcriptional regulation and apoptosis,Dipsaci Radix regulated cancer pathways and signaling pathways of toxoplasmosis,Kaposi sarcoma-associated herpesvirus infection,hepatitis B,colorectal cancer,lipids of small cell lung cancer, atherosclerosis, and estrogen to treat OPF. Molecular docking results showed that the active ingredients of Dipsaci Radix (E,E) -3,5-Di-O-caffeoylquinic acid,Gentianine,Cauloside A_qt, β- sitosterol had good affinity with CASP3, β2- adrenergic receptor gene (ADRB2) and CASP8. Conclusion: Dipsaci Radix can be used to treat OPF by directly acting on the pathways related to bone metabolism and participating in the regulation of multiple upstream and downstream signaling pathways. CASP3 and cancer pathways can be the key targets and pathways for the treatment of OPF.

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阮家坚,刘金城,蔡东岭,郭伟俊,魏其鹏,向振,董文暄,陈晓峰.基于网络药理学和分子对接探讨续断治疗骨质疏松性骨折作用机制[J].新中医,2024,56(5):200-206

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  • 在线发布日期: 2024-03-14
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