基于“物质-功效”关联性研究醋南柴胡抗抑郁药效物质  

Antidepressant pharmacodynamic substances of vinegar-baked Bupleurum scorzonerifolium based on correlation between substance and efficacy

作　　者：李泽浩 吴双 刘琳[1] 王冬雪[1] 杨雪晶[1] 盛洁静[1] 邹翔 曲中原[1] LI Zehao;WU Shuang;LIU Lin;WANG Dongxue;YANG Xuejing;SHENG jiejing;ZOU Xiang;QU Zhongyuan(College of Pharmacy,Harbin University of Commerce,Harbin 150076,China;Pharmaceutical Engineering Technology Research Center,Harbin University of Commerce,Harbin 150076,China)

机构地区：[1]哈尔滨商业大学药学院,黑龙江哈尔滨150076 [2]哈尔滨商业大学药物工程技术研究中心,黑龙江哈尔滨150076

出　　处：《中草药》2024年第24期8353-8365,共13页Chinese Traditional and Herbal Drugs

基　　金：黑龙江省自然科学基金联合基金培育项目(PL2024H196)。

摘　　要：目的研究醋南柴胡Bupleurum scorzonerifolium抗抑郁潜在的药效物质。方法采用超高效液相色谱-飞行时间质谱联用(UPLC-Q-TOF-MS)技术,对南柴胡醋炙前后化学成分变化进行全景分析及主成分分析(principal component analysis,PCA),找出差异成分;建立慢性温和不可预测性应激(chronic unpredictable mild stress,CUMS)抑郁大鼠模型,以行为学数据及脑中5-羟色胺(5-hydroxytryptamine,5-HT)、去甲肾上腺素(noradrenaline,NE)及多巴胺(dopamine,DA)含量为评价指标,对醋炙前后的抗抑郁作用进行比较研究;进一步通过网络药理学预测抗抑郁机制及其相关药效物质;建立斑马鱼抑郁模型,检测给药各组斑马鱼行为学数据及5-HT水平,对相关通路进行实验验证。结果醋南柴胡鉴定出38个成分,其中与生品共有37个。醋炙后13个成分含量发生变化,柴胡皂苷b1(saikosaponin b1,SSb1)、柴胡皂苷b2(saikosaponin b2,SSb2)、秦皮素和矮牵牛素含量升高,柴胡皂苷a(saikosaponin a,SSa)、柴胡皂苷c(saikosaponin c,SSc)、柴胡皂苷d(saikosaponin d,SSd)、异鼠李素-3-O-β-D-葡萄糖苷、异绿原酸A/B/C、柴胡皂苷k(saikosaponin k,SSk)、柴胡皂苷p(saikosaponin p,SSp)、异鼠李素和水仙苷含量降低。醋炙产生了柴胡次皂苷prosaikogenin A/D/G/F。与模型组相比,醋南柴胡组和南柴胡组大鼠体质量、糖水偏好度、旷场实验得分显著增加(P<0.05、0.01),脑内5-HT、NE、DA含量显著上升(P<0.05、0.01),醋南柴胡组优于南柴胡组。网络药理学预测IL-17信号通路是抗抑郁关键通路,相关药效物质为SSa、SSd、SSb1、SSb2。醋南柴胡及单体皂苷均可提升斑马鱼抑郁模型的运动距离和运动次数,升高体内5-HT含量(P<0.05,0.01);逆转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)结果显示均可通过下调白介素-17(interleukin-17,IL-17)、肾素血管紧张素系统(renin-angiotensin system,RAS)、蛋白激酶(raf protein kinase,RAObjective To study the potential antidepressant pharmacodynamic substances of vinegar-baked Bupleurum scorzonerifolium.Methods UPLC-Q-TOF-MS/MS technique was used to qualitatively analyze the chemical constituent change of B.scorzonerifolium(BS)before and after stir-baking with vinegar,principal component analysis(PCA)was performed to find out differential components.After establishing rat model of chronic mild and unpredictable stress(CUMS),the behavioral data and the contents of 5-hydroxytryptamine(5-HT),noradrenaline(NE),dopamine(DA)in the brain of depressed rats would be the evaluation indexes in order to comparatively study the antidepressant effects among raw and vinegar-baked products;furthermore,the antidepressant mechanism and their associated pharmacodynamic substances were predicted through network pharmacology;establishing a zebrafish depression model to detect the behavioral data and the level of 5-HT in zebrafish,then relevant pathways were verified experimentally.Results There were 38 components of vinegar-baked B.scorzonerifolium(VBS)were identified,37 of which were common components with raw products.The contents of 13 components changed after vinegar processing,four compounds content increased,including saikosaponin b1(SSb1),SSb2,fraxetin and petunia,and the contents of saikosaponin a(SSa),saikosaponin c(SSc),saikosaponin d(SSd),isorhanin 3-O-β-D-glucoside,isochlorogenic acid A/B/C,saikosaponin k(SSk),saikosaponin p(SSp),isorhamnetin and narcissus were decreased.In addition,vinegar-producing emerged prosaikogenin A/D/G/F.Compared with model group,the body weight,sugar-water preference,open field test score and intracerebral 5-HT,NE and DA contents of rats in BS and VBS significantly increased(P<0.05,0.01),VBS group was superior to the BS group.Network pharmacology predicted that IL-17 signaling pathway was the key pathway to antidepression and SSa,SSd,SSb1,and SSb2 were potential antidepressant pharmacodynamic substances.VBS and saikosaponins could improve the distance and rate of the depressed

关 键 词：南柴胡 醋南柴胡 抗抑郁作用 药效物质 柴胡皂苷b1 柴胡皂苷b2 秦皮素 矮牵牛素 水仙苷 

分 类 号：R284.1[医药卫生—中药学]