基于“化学成分-药效作用-靶点通路”模式研究“药引”茶叶对川芎茶调散“速而有效”制剂特征的影响

Chuanxiong Chatiao Powder first recorded in the “Formulary of Peaceful Benevolent Dispensary”, which is the classical prescription for treating migraine. Based on the previous study of zebrafish behavioral evaluation for migraine, we hypothesize that the tea may help to guide the active ingredient group of Chuanxiong Chatiao Powder through the blood-brain barrier to take effect. Studies on chemical constitutions across the blood-brain barrier in the rat models after application with Chuanxiong Chatiao Powder will be conducted to clarify the main active ingredient group of the preparation by using UPLC-Q-TOF-MS/MS and GC-MS; to screen the pharmacodynamic targets and find out the endogenous pathway, and further to uncover the underlying mechanism of formulations for transdermal absorption feature of Chuanxiong Chatiao Powder, metabolomics research on migraine animal model with or without ( before and after ) treating Chuanxiong Chatiao Powder will be carred out; All data will be analysed by using multi-factor interaction analysis together with neural network and interactive game theory to establish the “ingredients-efficacy-targets” model; Finally, to elucidate Chuanxiong Chatiao Powder’s preparation characteristics of “fast and effect” using the model, and further to provide new visions for the modernization of traditional Chinese medicine research.

川芎茶调散首载于《太平惠民和剂局方》，是治疗偏头痛经方，为传统风药配伍典范。基于申请人前期斑马鱼行为学评价模型试验提出假说：“川芎茶调散处方中，通过药引茶叶使其活性成分群透过血脑屏障‘上行头颠’而显效”。课题采用UPLC-Q-TOF-MS/MS、GC-MS技术对川芎茶调散灌胃大鼠前后透过血脑屏障的化学组分进行研究，筛选其活性组分群；应用UPLC-ESI-Q-TOF-MS/MS、GC-MS技术对偏头痛动物模型给药前后进行代谢组学研究，筛选其药效作用靶点，探明其内源性作用通路，研究川芎茶调散具有制剂透皮吸收特征的作用机制；采用神经网络、博弈理论进行多因素交互分析，构建“化学成分-药效作用-靶点通路”研究模型；最后利用构建的该评价模型阐释川芎茶调散“速而有效”的制剂特征，为中药复方的现代化研究提供新思路。

川芎茶调散首载于《太平惠民和剂局方》，是治疗偏头痛经方，其以“风药配伍”，乃“去急病用之”，为传统风药配伍典范。该方以茶叶作为“药引”，通过具有促透作用的物质透过血脑屏障达到“速而有效”的治疗目的。课题通过小鼠甩尾实验、小鼠热板实验和斑马鱼行为学实验证实了茶叶的加入使得川芎茶调散在偏头痛的治疗上显效迅速，且疗效显著，具有“速而有效”的制剂特征，且茶水本身具备一定的镇痛效果；采用酶联免疫法(ELISA)测定小鼠血浆中和脑组织中CGRP、5-HT、ET- 1的含量，证明了茶叶的加入可通过影响小鼠脑组织中5-HT，小鼠血液中和脑组织中ET- 1的浓度而增强川芎茶调散的药效作用；应用UPLC-ESI-Q-TOF-MS/MS技术对小鼠偏头痛模型给药成分进行分析，从脑组织样本分离出川芎茶调散全方组和缺方组之间有含量差异的化合物24种，包括DL-色氨酸、3-硫酸吲哚酚硫酸盐、DL-4-羟基苯乳酸、N乙酰-天冬氨酸、乙酰左旋肉碱等；从血液样本分离出全方组和缺方组之间有含量差异的化合物52种，包括犬尿喹啉酸、DL-色氨酸、鸟嘌呤、N-乙酰-L-酪氨酸、茶碱等，证明了茶叶的加入对川芎茶调散入血和入脑成分产生了一定影响，但其具体作用机理，尚待进一步实验研究。