目的 基于斑马鱼模型探究晕痛定胶囊的镇痛活性,采用网络药理学方法预测晕痛定胶囊的镇痛作用机制。方法 采用佛波酯构建斑马鱼疼痛模型,以阿司匹林为阳性对照,利用行为轨迹分析系统监测斑马鱼的运动轨迹,以运动次数、运动时间、运动距离、运动速度等运动状态为指标评价晕痛定胶囊及其组方药材的镇痛活性;同时运用网络药理学及分子对接技术预测晕痛定胶囊镇痛核心成分及潜在靶点;选取网络药理学预测的核心成分法卡林二醇和金色酰胺醇酯为实验药物,利用斑马鱼疼痛模型验证镇痛活性。结果 斑马鱼疼痛模型镇痛活性评价实验中,晕痛定胶囊及其组方药材川芎、蜜环菌均能显著降低模型斑马鱼的快速运动和慢速运动(P＜0.01),且晕痛定胶囊作用强于川芎和蜜环菌。网络药理学筛选得到晕痛定胶囊镇痛活性成分87个及其作用靶点159个,利用蛋白质-蛋白质相互作用(PPI)网络分析得到法卡林二醇和金色酰胺醇酯等核心成分和MAPK1等核心靶点,分子对接结果显示核心成分及核心靶点间具有较好的结合活性。法卡林二醇和金色酰胺醇酯镇痛活性实验结果表明单独给药法卡林二醇和金色酰胺醇酯可以达到良好的镇痛效果,与网络药理学预测的核心成分结果相符。结论 晕痛定胶囊能够缓解暴露于佛波酯中斑马鱼的疼痛状态,具有较明显的镇痛作用;预测其作用机制可能与减少神经损伤及其炎症反应和促进细胞凋亡等过程有关;且法卡林二醇和金色酰胺醇酯为其发挥镇痛作用的核心成分。

Objective To explore the analgesic activity of Yuntongding Capsules(YTD) based on zebrafish model and analgesic mechanism of Yuntongding Capsules by network pharmacology.Methods Phorbol myristate acetate(PMA) was used to establish a zebrafic pain model, and aspirin was used as positive control. The movement trajectory of zebrafish was monitored with the behavior trajectory analysis system and the analgesic activity of YTD was evaluated by the movement states such as movement frequency,movement time, movement distance and movement speed. Network pharmacology and molecular docking techniques were used to predict the core components and potential analgesic mechanism of YTD. Selecting network pharmacology prediction components of falcarindiol(Fal) and aurantiamide acetate(Aur) as the experimental drugs to verify the network pharmacology prediction results.Results By comparing the exercise intensity and trajectory of zebrafish in the model group and each administration groups, YTD has better analgesic activity, and it is better than the analgesic effect of Ligusticum or Armillaria mellea alone. 87 active components and 159 action targets of YTD analgesia were screened by network pharmacology. Core components such as Aur and core targets such as MAPK1 were obtained by protein-protein interaction network analysis and molecular docking was performed, showing that the core component targets had good binding activity. Data from the Fal and Aur groups suggest that favorable analgesia can be achieved by administering Fal or Aur alone. This is consistent with the results of network pharmacology.Conclusion YTD can alleviate the pain of zebrafish exposed to PMA and has obvious analgesic effect. Predicting its mechanism of action may be related to processes such as reducing nerve damage and inflammatory response, and promoting cell apoptosis. At the same time, Fal and Aur are the core components that exert analgesic effects, providing a foundation for the research and development of new analgesic drugs in the future.

R285.5

北京中医药大学新教师启动基金资助项目(2020-JYB-XJSJJ-009)