高级检索

    基于UPLC-Orbitrap Fusion Lumos Tribrid-MS、网络药理学与实验验证的正骨紫金丸活性成分及作用机制研究

    Study on the Active Ingredients and Mechanism of Action of Zhenggu Zijin Wan Based on UPLC-Orbitrap Fusion Lumos Tribrid-MS, Network Pharmacology, and Experimental Validation

      摘要
    • 摘要:
      目的 基于UPLC-Orbitrap Fusion Lumos Tribrid-MS联合网络药理学与实验验证预测正骨紫金丸活血化瘀的活性成分及其作用机制。
      方法 首先，采用UPLC-Orbitrap Fusion Lumos Tribrid-MS快速表征正骨紫金丸中的化学成分；其次，通过网络药理学的研究方法构建“药物-成分-靶点”网络，获取关键靶点及主要活性成分，结合String平台与CytoScape软件构建蛋白质-蛋白质相互作用(protein-protein interaction，PPI)网络，通过MateScape数据库富集分析通路，利用DiscoVery Studio 4.5软件进行分子对接验证；最后，建立急性软组织损伤动物模型，以急性软组织损伤评分与全血黏度为药效学指标开展药效学研究。
      结果 正骨紫金丸中共鉴定出包括黄酮类、生物碱类、有机酸类和香豆素类等化合物67个，其中大黄素、藁本内酯、肉桂酸、水杨酸、芦荟大黄素可能为正骨紫金丸活血化瘀的主要活性成分。PPI网络拓扑分析得到TNF、ALB、AKT1等 26个核心靶点，KEGG 富集分析表明正骨紫金丸主要通过调控TNF、PI3K-Akt、NF-κB等信号通路发挥活血化瘀作用，分子对接结果显示正骨紫金丸主要活性成分与关键靶点结合良好，药效学结果表明正骨紫金丸可显著降低急性软组织损伤大鼠的全血黏度。
      结论 本研究明确了正骨紫金丸活血化瘀的活性成分和作用机制，同时表明其可能通过作用于多靶点、多通路整体调节，共同发挥活血化瘀作用，为其后续深入研究提供参考。

       

      Abstract:
      OBJECTIVE To predict the active ingredients and mechanism underlying the blood circulation-promoting and stasis-resolving effects of Zhenggu Zijin Wan using UPLC-Orbitrap Fusion Lumos Tribrid-MS, network pharmacology, and experimental validation.
      METHODS  Firstly, UPLC-Orbitrap Fusion Lumos Tribrid-MS was employed to rapidly characterize the chemical components in Zhenggu Zijin Wan. Secondly, a “drug-component-target” network was constructed through network pharmacology research methods to obtain key targets and major active components. The protein-protein interaction(PPI) network was constructed by combining the String platform and CytoScape software. Pathway enrichment analysis was conducted through the MateScape database, and molecular docking verification was performed using DiscoVery Studio 4.5 software. Finally, an animal model of acute soft tissue injury was established, and pharmacodynamic studies were conducted using acute soft tissue injury scores and whole blood viscosity as pharmacodynamic indicators.
      RESULTS A total of 67 compounds including flavonoids, alkaloids, organic acids, and coumarins were identified in Zhenggu Zijin Wan. Among them, emodin, ligustilide, cinnamic acid, salicylic acid, aloe emodin, and others might be the main active ingredients for promoting blood circulation and removing blood stasis in Zhenggu Zijin Wan. PPI network analysis revealed 26 core targets such as TNF, ALB, AKT1. KEGG enrichment analysis showed that Zhenggu Zijin Wan mainly regulated TNF, PI3K-Akt, NF-κB signaling pathway played a role in promoting blood circulation and resolving stasis. And molecular docking results showed that the main active ingredients of Zhenggu Zijin Wan bound well with key targets. The pharmacodynamic results indicated that Zhenggu Zijin Wan could significantly reduce the whole blood viscosity in rats with acute soft tissue injury.
      CONCLUSION The study preliminarily clarifies the active ingredients and mechanism of action of Zhenggu Zijin Wan in promoting blood circulation and resolving blood stasis, and indicates that it may exert the effect of promoting blood circulation and resolving blood stasis together by acting on multiple targets and pathways, providing reference for its future in-depth research.

       

      • HTML全文
      • 参考文献(29)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回