基于网络药理学研究大川芎方治疗偏头痛的作用机制

Network-assisted Investigation into Mechanism of Dachuanxiong Fang on Migraine

目的研究大川芎方治疗偏头痛的分子作用机制。方法结合文献挖掘、分子对接和网络分析研究大川芎方中化合物群与偏头痛相关靶蛋白的相互作用。结果分子对接发现大川芎中有38个活性成分,且大部分具有较好的口服生物利用度和良好的脑内暴露量,进一步网络分析发现senkyunolide M,riligustilide,levistolide A,chuanxiongterpene等16个化合物为其主要活性成分,可通过与CGRP、p38、TNF-α、iGluR5、NOS等18个靶蛋白作用,抑制神经源性炎症和神经递质的产生,降低源自三叉神经的感受器对伤害性信息的超敏化,并对抗皮层扩布性抑制,从而发挥治疗偏头痛的作用。结论通过网络分析明确了大川芎方治疗偏头痛的分子作用机制,诠释了其科学内涵,有助于推动后续相应制剂的药效物质基础研究和分子机制实验研究。

OBJECTIVE To understand the mechanism of Dachuanxiong Fang on migraine.METHODS Data mining,Molecular docking and Network Analysis were employed to investigate the active compounds and key target protein.RESULTS38 active hits were identified by virtual screening,of which,most compounds had good oral bioavailability and might be optimal CNS exposure.Among them,16molecules（senkyunolide M,levistolide A,chuanxiongterpene,riligustilide,etc.）could significantly contribute to alleviate migraine.And they could target 18protein（such as CGRP,p38,TNF-α,iGluR5,NOS）to inhibit neurogenic inflammation and neutrotransmitters,to reduce the sensitive of nociceptors originated in the trigeminal ganglion,and to combat the genesis and propagation of cortical spreading depression.CONCLUSION It was illustrated the molecular mechanism and the key active compounds of Dachuanxiong Fang,which was helpful for wet experiments to explore targets and active compounds.