目的 阐明治疗偏头痛的传统方剂吴茱萸汤（Wuzhuyu Decoction）的有效成分和作用机制。方法 利用单向在体肠灌流方法获得10种WZYD在体吸收成分谱，同时建立利血平致偏头痛小鼠模型，检测血清与脑组织中一氧化氮及其合成酶水平及脑组织内5-羟色胺、去甲肾上腺素、多巴胺的含量，将吸收谱与药效指标进行谱效相关分析，确定影响药效的主要成分。结合网络药理学方法对吴茱萸汤治疗偏头痛的有效活性成分和潜在作用靶点进行分析，获得潜在治疗靶点以及生物学过程等，并对网络中的关键靶点和成分进行分子对接。结果 吴茱萸汤中9种在体吸收成分对药效指标具有不同的作用，综合药效趋势中，吸收含量越高作用越好的前3位成分为吴茱萸苦素（rutaevine，Rv）、柠檬黄素-3-O-β-D-葡萄糖苷（limocitrin-3-O-β-D-glucoside，Lcs）、吴茱萸次碱（rutaecarpine，Ru），吸收含量越低作用越好的前3位成分为6-姜辣素（6-gingerol，6-Gi）、吴茱萸碱（evodiamine，Ev）、人参皂苷Rg₁（ginsenoside Rg₁，Rg₁）。网络药理学分析，吴茱萸汤作用于前列腺素内过氧化物合成酶2、5-羟色胺转运体、瞬时受体电位香草酸亚型1等受体蛋白，涉及118个生物学过程、21个细胞组分、21个分子功能和24条信号通路。结论 吴茱萸汤中活性成分的吸收量与药效存在相关关系，可能是通过抑制神经源性炎症、影响5-羟色胺能信号通路的传导发挥治疗作用。

Objective To clarify the effective composition and mechanism of a traditional formula Wuzhuyu Decoction (WZYD, 吴茱萸汤) in treatment of migraine. Methods In this study, the spectrum-effect relationships between 10 kinds of WZYD absorption component spectrum using the single pass intestinal perfusion and migraine related efficacy were analyzed to determine the main components that affect the efficacy, such as NO and NO Synthetase in serum and brain, 5-hydroxytryptamine, dopamine, norepinephrine in brain tissue. And the components and mechanism of WZYD were explored in the treatment of migraine by network pharmacology. Then the active ingredients and potential targets were analyzed to obtain therapeutic targets and biological processes through network pharmacology, and carry out molecular docking of key targets and components in the network. Results The results indicated that nine components absorbed of WZYD had different effects to pharmacodynamics index. In the comprehensive efficacy trend, the effects of some ingredients were positively correlated with absorption, such as rutaevine, limocitrin-3-O-β-D-glucoside and rutaecarpine; while the effects of others were negatively correlated with absorption, such as 6-gingerol, evodiamine and ginsenoside Rg₁. WZYD acted on PTGS2, SLC6A4, and TRPV1 and 118 biological processes, 21 celular components, 21 molecular functions and 24 signaling pathways were involved. Conclusion There is a correlation between the absorption of active components in WZYD and its efficacy. WZYD may play a therapeutic role by inhibiting neurogenic inflammation and the conduction of 5-HT signaling pathway.

R285

国家自然科学基金面上项目（81473360）