基于网络药理学方法的元胡止痛滴丸治疗原发性痛经的配伍合理性研究

目的探究元胡止痛滴丸治疗原发性痛经的配伍合理性。方法选取元胡止痛滴丸中延胡索生物碱类代表成分延胡索乙素、巴马汀、海罂粟碱、原阿片碱以及白芷香豆素类代表成分欧前胡素和异欧前胡素为研究对象,利用网络药理学的方法对6个化合物的潜在作用靶点和通路进行预测,并利用分子对接技术对预测结果进行验证,通过数据整合,剖析元胡止痛滴丸的作用机制及配伍规律。结果 6个化合物可作用于23个潜在的蛋白靶点和19条相关通路。作用通路涉及中枢镇痛、激素调节、解痉、血管舒张、炎症及免疫等各个环节,2类成分既有共同的作用靶点群及通路群,又各有偏重,各通路群间通过共有靶点连接,显示出不同成分间的多靶点、多途径的协同作用。结论延胡索通过作用于中枢镇痛、平滑肌相关受体蛋白以及血栓素、血管紧张素等靶点蛋白而发挥止痛、理气、活血等功效,起到君药的作用。白芷通过参与痉挛、炎症等相关信号通路的调节与转导,发挥宣湿痹行气血的功效,辅助君药延胡索起到臣药作用,体现了二者配伍的合理性。

Study on compatibility rationality of Yuanhu Zhitong Dropping Pills for treatment of primary dysmenorrhea based on network pharmacology

Objective To explore the compatibility rationality of Yuanhu Zhitong Dropping Pills (YZDP) for the treatment of primary dysmenorrhea. Methods The potential targets and pathways of tetrahydropalmatine, palmatine, glaucine, protopine, imperatorin, and isoimperatorin, selected as the representative compounds of alkaloid and coumarin from Corydalis Rhizoma and Angelicae Dahuricae Radix, were predicted by the methods of network pharmacology. The results were verified by docking and the mechanism and compatibility regularity of YZDP were analyzed by integrating all the data. Results The in silico prediction results showed that the six compounds of YZDP affected 19 related pathways through 23 target proteins. The pathways were involved in central analgesia, hormonal regulation, spasmolysis, vasodilatation, inflammation, and immunoregulation. The alkaloid and coumarin showed common targets and pathways but also had their own emphasis. The pathways were connected by the common targets, showing the synergistic effect of different compounds by acting on multi-targets and multi-pathways. Conclusion Corydalis Rhizoma acts as monarch drug, showing the effect of analgesia, regulating qi, and activating blood by acting on thromboxane receptors, angiotensin receptors, and targets related with central analgesia and spasmolysis. Angelicae Dahuricae Radix, showing the effect of regulating qi, and activating blood by regulating the pathways of spasm, inflammation, and so on, acts as ministerial drug to assist monarch drug to enhance treatment which reflected the compatibility rationality of Corydalis Rhizoma and Angelicae dahuricae Radix.