在体吸收谱效相关研究吴茱萸汤治疗偏头痛活性成分  

Study on pharmacological ingredients of Wuzhuyu Decoction in treatment of migraine by correlating in vivo absorption spectrum-effect relationship

作　　者：南楠 许永崧 李美景 龚慕辛[1,2] 郭中原 徐睿[1,2] 骆思源 王智民 NAN Nan;XU Yong-song;LI Mei-jing;GONG Mu-xin;GUO Zhong-yuan;XU Rui;LUO Si-yuan;WANG Zhi-min(School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China;Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research,Beijing 100069,China;Center for Endocrine Metabolism and Immune Diseases,Beijing Luhe Hospiital,Capital Medical University,Beijing 101149,China;Beijing Key Laboratory of Diabetes Research and Care,Beijing 101149,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Pharmacy,Henan University of Traditional Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]首都医科大学中医药学院,北京100069 [2]中医络病研究北京市重点实验室,北京100069 [3]首都医科大学附属北京潞河医院内分泌代谢与免疫性疾病中心,北京101149 [4]糖尿病防治研究北京市重点实验室,北京101149 [5]中国中医科学院中药研究所,北京100700 [6]河南中医药大学药学院,河南郑州450046

出　　处：《中草药》2021年第19期5956-5970,共15页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金面上项目(81473360)。

摘　　要：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Rg_(1)(ginsenoside Rg_(1),Rg_(1))。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 Rg_(1). WZYD acted on PTGS2, SLC6 A4, 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.

关 键 词：偏头痛 吴茱萸汤 单向在体肠灌流 谱效相关 网络药理学 吴茱萸苦素 柠檬黄素-3-O-β-D-葡萄糖苷 吴茱萸次碱 6-姜辣素 吴茱萸碱 人参皂苷RG 

分 类 号：R285[医药卫生—中药学]