基于UPLC-QTOF-MS、生物信息学和分子动力学模拟的百令胶囊治疗多囊卵巢综合征的质量标志物研究

The quality markers study of Bailing capsule in the treatment of polycystic ovary syndrome based on UPLC-QTOF-MS, bioinformatics and molecular dynamics simulation

关键词:  百令胶囊  入血成分  生物信息学  分子对接  分子动力学  药效物质

Key words:  bailing capsule  constituents absorbed in blood  bioinformatics  molecular docking  molecular dynamics  pharmacodynamic substances

摘要:

目的 采用UPLC-QTOF-MS、生物信息学、分子对接和分子动力学模拟(MD)探究百令胶囊(BL)治疗多囊卵巢综合征(PCOS)的质量标志物(Q-marker)。方法 采用UPLC-QTOF-MS技术分析BL的入血成分,通过PeakView软件结合化学成分数据库信息辅助鉴定入血原型成分。以入血成分作为候选化合物,运用生物信息学方法预测主要作用靶点及通路,使用Cytoscape软件构建“药物-成分-靶点-通路”网络。最后通过分子对接和分子动力学模拟(MD)对结果进行验证。结果 共筛选出BL治疗PCOS的12个主要成分,18个关键靶点和7条相关通路。预测亚油酸、亚麻酸、花生四烯酸等潜在入血成分是BL治疗PCOS的主要药效物质,并通过AR、PPARG等靶点影响代谢和激素相关通路发挥作用。分子对接显示亚油酸、亚麻酸和花生四烯酸与核心靶点AR的Total Score得分分别为8.9953、8.5093、8.8772；与核心靶点PPARG的Total Score得分分别为9.2277、9.0066、8.8948。MD结果进一步说明分子对接条件可靠且以上成分与靶点结合稳定。结论 BL可能通过亚油酸、亚麻酸和花生四烯酸等多成分,调节AR、PPARG等多靶点发挥治疗PCOS的效果,这为后续深入研究提供新思路。

Abstract:

PURPOSE Exploration of quality markers (Q-markers) for the treatment of polycystic ovary syndrome (PCOS) with Bailing capsule (BL) using UPLC-QTOF-MS, bioinformatics, molecular docking and molecular dynamics simulation (MD). METHODS The TCMSP database, TCMBank database and China Knowledge Network (CNN) were used to establish the database of the chemical composition of BL. The UPLC-QTOF-MS technique was used to analyze the blood-entry components of BL, and the PeakView software was used to assist in the identification of the blood-entry prototype components in conjunction with the information from the chemical composition database. Using blood-entry components as candidate compounds, a targeted network pharmacology approach was used to predict the main targets and pathways, and a “drug-component-target-pathway” network was constructed using Cytoscape software. The results were finally validated by molecular docking and molecular dynamics simulation (MD). RESULTS By employing network pharmacology, this study identified a total of 14 blood-entry components within BL capsule. Subsequently, a screening process led to the identification of 12 principal components, along with 18 key targets and 7 associated pathways relevant to the treatment of PCOS. Based on the degree values between compounds, targets, and signaling pathways, it is initially predicted that potential blood-entry components such as linoleic acid, linolenic acid, and arachidonic acid may be the main pharmacological substance basis of BL for the treatment of PCOS and act through targets such as target AR and PPARG to influence metabolism and hormone-related pathways. Molecular docking showed that the Total Score scores of linoleic acid, linolenic acid and arachidonic acid with the core target AR were 8.9953, 8.5093, and 8.8772, respectively; and the Total Score scores with the core target PPARG were 9.2277, 9.0066, and 8.8948, respectively. The MD results further demonstrate that the molecular docking conditions were reliable and the binding of the above constituents with the targets were stable. CONCLUSION In this study, we predicted the main pharmacodynamic substances and mechanisms of BL in the treatment of PCOS by blood entry component analysis combined with bioinformatics, which provides new ideas for subsequent in-depth research.