基于“五原则”结合蛛网模型辨析肺热止咳颗粒质量标志物

Discrimination of Quality Markers of Feire Zhike Granule Based on Five Principles Coupled with Cobweb Model

关键词:  肺热止咳颗粒  质量标志物  五原则  蛛网模式  网络药理

Key words:  Feire Zhike granules  Q-Marker  five principles  cobweb model  network pharmacology

摘要:

目的 以质量标志物(quality markers，Q-Marker)“五原则”为指导，结合质谱、网络药理学和蛛网模型等手段，开展肺热止咳颗粒治疗咳嗽的Q-Marker研究。方法 采用液质联用技术辨析肺热止咳颗粒中主要化学成分；检索TCMSP数据库收集肺热止咳颗粒处方中11味药材活性成分和对应靶点，同时检索GeneCards数据库收集咳嗽相关蛋白编码基因，构建药材-成分-靶点网络图，根据靶点数对活性成分进行有效性赋值；查阅药典和文献，获得各味药材可测性成分；基于配伍原则，确定原药材在复方中的君臣佐使归属；检索文献和TCMSP数据库筛选原药材特有性成分。结果 基于UHPLC-Q-TOF-MS/MS共鉴定肺热止咳颗粒中43个化学成分可“传递”至制剂中；从TCMSP数据库中筛选获得124个活性化合物，并作用于120个靶标，其中93个靶标与咳嗽相关；药典中载明定量方法的成分有6个；复方中11味药材特有性成分26个；另结合君臣佐使配伍规则和蛛网模式赋分规则为上述成分打分排序，前10个成分分别为汉黄芩素、黄芩素、甘草查尔酮A、川陈皮素、金合欢素、橙皮苷、甘草苷、对叶百部碱、β-谷甾醇和高良姜素。结论 该10个成分可以作为肺热止咳颗粒的Q-Marker。

Abstract:

OBJECTIVE To conduct a quality markers(Q-Markers) study on the treatment of cough with Feire Zhike granules based on the “five principles” of Q-Markers, combined with mass spectrometry, network pharmacology and cobweb model. METHODS Identification of the main chemical components in Feire Zhike granules by liquid mass spectrometry. The TCMSP database was searched to collect the active ingredients and corresponding targets of 11 herbs in the prescription of Feire Zhike granules. The GeneCards database was also searched to collect genes encoding cough-related proteins, and a herb-component-target network map was constructed. Assigning effectiveness to active ingredients based on the number of target sites. Check the pharmacopoeia and literature to obtain the measurable components of each herb. Determine the monarchical, ministerial and adjuvant attribution of the original herbs in the compound formula based on the principle of compatibility. The literature and TCMSP database were searched to screen the original herb for specificity components. RESULTS A total of 43 chemical components in the Feire Zhike granules were identified to be “delivered” to the formulation based on UHPLC-Q-TOF-MS/MS. The 124 active compounds were obtained from the TCMSP database and acted on 120 targets, 93 of which were associated with coughing. There were 6 components in the pharmacopoeia that specify quantitative methods. A total of 26 endemic components were found in 11 herbs in the compound formula. In addition, the above components were ranked according to the compatibility rules of monarch and minister and the scoring rules of cobweb model. The top 10 components were wogonin, baicalein, licochalcone A, nobiletin, acacetin, hesperidin, liquiritin, tuberstemonine, β-sitosterol and galangin, respectively. CONCLUSION The above 10 components can be identified as Q-Markers of Feire Zhike granules.