基于代谢组学和网络药理学的蜡梅类黄酮组分评价

Evaluation of flavonoids in Chimonanthus praecox based on metabolomics and network pharmacology

摘要:

类黄酮是蜡梅发挥药理活性的关键功效成分。为了探究蜡梅类黄酮的潜在功效成分及发挥药理活性的作用机制，本研究基于超高效液相色谱-串联质谱的广泛靶向代谢组学技术全面鉴定蜡梅的类黄酮组分，结合网络药理学挖掘蜡梅功效类黄酮组分及其作用机制，利用分子对接进一步验证网络预测结果，最后进行不同品种蜡梅功效类黄酮含量评估。蜡梅广靶代谢分析中共鉴定出387种类黄酮组分，不同品种蜡梅在黄酮类代谢物上存在显著差异。网络药理学分析鉴定出96种中药化学成分，19种功效活性物质，181个对应靶点，2 504个疾病靶点，99个交集靶点，33个核心靶点，涉及229个基因功能条目和99条通路(P≤0.05)，显示出蜡梅类黄酮成分在抗氧化、抗炎、杀菌、抗病毒等方面的药理活性。拓扑分析筛选出三裂鼠尾草素、西伯利亚落叶松黄酮、异鼠李素、槲皮素、6-羟基木犀草素共5个核心成分与SRC、PIK3R1、AKT1、ESR1、AKR1C3共5个核心靶点。蜡梅功效类黄酮能够稳定地与关键作用靶点结合，表明这些黄酮类化合物在与靶点的相互作用中具有潜在的生物活性。蜡梅类黄酮代谢产物发挥药理活性的作用机制具有多成分、多靶点和多通路的特点，代谢组学和网络药理学的交叉应用可为深入研究蜡梅的药理功效和治疗机制提供理论依据。

关键词:蜡梅;类黄酮;分子对接;代谢组学;网络药理学

Abstract:

Flavonoids are key bioactive components for evaluating the pharmacological activities of Chimonanthus praecox. Exploring the potential flavonoids and pharmacological mechanisms of C. praecox lays a foundation for the rational development and efficient utilization of this plant. This study employed ultra-performance liquid chromatography-tandem mass spectrometry-based widely targeted metabolomics to comprehensively identify the flavonoids in C. praecox. Network pharmacology was employed to explore the bioactive flavonoids and their mechanisms of action. Molecular docking was adopted to validate the predicted results. Finally, the content of bioactive flavonoids in different varieties of C. praecox was measured. The widely targeted metabolomics analysis identified 387 flavonoids in C. praecox, and the flavonoids varied among different varieties. Network pharmacology predicted 96 chemical components including 19 bioactive compounds, 181 corresponding targets and 2 504 disease targets, among which 99 targets were shared by the active components and the disease. Thirty-three core targets were predicted, involving 229 gene ontology terms and 99 pathways (P≤0.05), which indicated that the flavonoids components of C. praecox exhibited pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, and antiviral activities. Topological analysis screened out five core components (salvigenin, laricitrin, isorhamnetin, quercetin, and 6-hydroxyluteolin) and five core targets (SRC, PIK3R1, AKT1, ESR1, and AKR1C3). The predicted bioactive flavonoids from C. praecox stably bound to key targets, which indicated that these flavonoids possessed potential bioactivities in their interactions with the targets. The flavonoids in C. praecox exerted pharmacological activities in a multi-component, multi-target, and multi-pathway manner. The combined application of metabolomics and network pharmacology provides a theoretical basis for in-depth studies on the pharmacological effects and mechanisms of C. praecox.

Key words:Chimonanthus praecox;flavonoids;molecular docking;metabolomics;network pharmacology