基于网络药理学和Box-Behnken响应面法优化养心颗粒提取工艺

Optimization of the Extraction Process of Heart-nourishing Granule Based on Network Pharmacology and Box-Behnken Response Surface Method

关键词:  养心颗粒  网络药理学  层次分析法  Box-Behnken响应面法  提取工艺

Key words:  heart-nourishing granule  network pharmacology  analytic hierarchy process  Box-Behnken response surface method  extraction process

摘要:

目的 通过网络药理学和Box-Behnken响应面法优化养心颗粒提取工艺。方法 通过网络药理学挖掘养心颗粒活性成分并初步探究其治疗冠心病的作用机制；分子对接技术预测活性成分与主要靶点的结合能力。同时结合该方君臣佐使配伍关系、成分药理作用及中国药典2020年版一部各药味含量测定指标成分，进一步确定养心颗粒工艺评价指标成分。此外，结合层次分析法确定各成分权重，Box-Behnken响应面法优化养心颗粒提取工艺。结果 筛选得到的养心颗粒主要活性成分为梓醇、地黄苷D、毛蕊花糖苷、阿魏酸和党参炔苷，通过作用于AKT1、IL-6、IL-1b、VEGFA、JUN、MAPK3等核心靶标，调节脂质和动脉粥样硬化、MAPK信号等通路共同发挥治疗冠心病的作用。分子对接结果表明，网络药理学预测的活性成分与核心靶点结合能均<-5.0 kJ·mol^-1。层次分析法计算得到5种成分梓醇、地黄苷D、毛蕊花糖苷、阿魏酸、党参炔苷权重系数分别为0.329 7，0.329 7，0.164 8，0.109 9，0.065 9，Box-Behnken响应面法得到最优水提工艺：采用10倍量的水提取2次，每次煎煮1.5 h。验证试验表明5种成分含量与预测值相符，RSD值均<5%。结论 基于网络药理学和Box-Behnken响应面法得到的养心颗粒提取工艺稳定可行，为其进一步质量提升提供了实验依据。

Abstract:

OBJECTIVE To optimize the heart-nourishing granule extraction process by network pharmacology and Box-Behnken response surface method. METHODS The active ingredients of heart-nourishing granule were excavated through network pharmacology and their mechanism of action in the treatment of coronary heart disease was preliminarily explored. Molecular docking technology was used to predict the binding ability of the active ingredients to the main targets. At the same time, based on the compatibility relationship between the monarch, minister, assistant and guide of the prescription, the pharmacological effects of the ingredients, and the content determination index components of each medicinal flavor in the 2020 edition of the Chinese Pharmacopoeia, the process evaluation index components of heart-nourishing granule were further determined. In addition, combined with the analytic hierarchy process to determine the weight of each component, the Box-Behnken response surface method was used to optimize the extraction process of heart-nourishing granule. RESULTS The main active components of heart-nourishing granule screened were catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin. By acting on core targets such as AKT1, IL-6, IL-1b, VEGFA, JUN and MAPK3, they regulated lipid and atherosclerosis, MAPK signaling and other pathways played a role in the treatment of coronary heart disease. Molecular docking results showed that the binding energies of active components and core targets predicted by network pharmacology were all < -5.0 kJ·mol^-1. Five components catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin were calculated by analytic hierarchy process method. The weight coefficients of arginyl glycosides were 0.329 7, 0.329 7, 0.164 8, 0.109 9, and 0.065 9, respectively. The Box-Behnken response surface method obtained the optimal water extraction process: 10 times the amount of water was used to extract twice, and each time was decocted for 1.5 h. The verification test showed that the contents of the five components were consistent with the predicted values, and the RSD values were all <5%. CONCLUSION The extraction process of heart-nourishing granule based on network pharmacology and Box-Behnken response surface methodology is stable and feasible, which provided an experimental basis for its further quality improvement.