黄芩抗斑马鱼焦虑的作用及靶向GABA受体的分子对接研究  

Effect of Scutellariae Radix on Zebrafish Anxiety and Molecular Docking Analysis Targeting GABA Receptor

作　　者：张文韬 潘豪杰 胡应宝 闫攀 徐秀泉 仝旭[1] 汤建 闻崇炜 ZHANG Wentao;PAN Haojie;HU Yingbao;YAN Pan;XU Xiuquan;TONG Xu;TANG Jian;WEN Chongwei(Bozhou University,Bozhou 236800,China;Jiangsu University,Zhenjiang 212013,China)

机构地区：[1]亳州学院,安徽亳州236800 [2]江苏大学,江苏镇江212013

出　　处：《中医药信息》2024年第8期9-13,19,共6页Information on Traditional Chinese Medicine

基　　金：安徽省高等学校自然科学研究项目(2022AH052414,2022AH052416);亳州学院大学生创新创业训练计划项目(2023XJXM066/8);亳州学院横向项目(BYH202107)。

摘　　要：目的:研究黄芩50%乙醇提取物对1-(3-氯苯基)哌嗪盐酸盐(mCPP)致焦虑的斑马鱼焦虑状态的治疗作用及可能的作用机制。方法:抗焦虑研究:选取受精后10、30 d的斑马鱼分为空白组、模型组(0.1 nmol/L mCPP)、给药组(不同浓度黄芩提取物+0.1 nmol/L mCPP),Zebralab软件分析斑马鱼的平均移动距离。采用分子对接软件Autodock Vina分析黄芩中的12种主要成分与γ-氨基丁酸A型受体(GABAAR)的结合能,初步确定潜在的活性组分。结果:黄芩50%乙醇提取物对mCPP诱导的受精后10、30 d斑马鱼焦虑均有抑制作用,其中受精后30 d斑马鱼空白组、模型组(0.1 nmol/L mCPP)和给药组(200µg/mL+0.1 nmol/L mCPP)的平均移动距离分别为3633、4280、3894 mm,说明200µg/mL黄芩提取物可以减缓0.1 nmol/L mCPP对受精后30 d龄斑马鱼的焦虑行为。同时斑马鱼的焦虑行为符合趋触性。11种黄芩活性成分与GABAAR结合能强于原配体地西泮的结合能(-7.2 kcal/mol),白杨素的结合力最强(-8.8 kcal/mol),主要成分黄芩素、黄芩苷、汉黄芩素和汉黄芩苷的结合力也较强,分别为-8.3、-7.7、-8.3、-7.3 kcal/mol。预测黄芩苷等黄酮类成分是黄芩治疗焦虑主要物质基础。结论:黄芩具有抗斑马鱼焦虑的确切疗效,其活性机制可能与黄芩黄酮类成分激活GABAAR有关。Objective:To investigate the therapeutic effects and potential mechanisms of the 50%ethanol extract of Scutellariae Radix on zebrafish anxiety induced by 1-(3-chlorophenyl)piperazine hydrochloride(mCPP).Methods:In the anxiolytic study,zebrafish at 10 and 30 days post-fertilization were divided into control group,model group(0.1 nmol/L mCPP),and treatment groups(different concentrations of Scutellariae Radix extract+0.1 nmol/L mCPP).Zebralab software was used to analyze the average movement distance of the zebrafish.Molecular docking software Autodock Vina was employed to analyze the binding energy between 12 main components of Scutellariae Radix and the gamma-aminobutyric acid A receptor(GABAAR),identifying potential active components.Results:The 50%ethanol extract of Scutellariae Radix inhibited mCPP-induced anxiety in zebrafish at both 10 and 30 days post-fertilization.For zebrafish at 30 days post-fertilization,the average movement distances for the control group,model group(0.1 nmol/L mCPP),and treatment group(200μg/mL+0.1 nmol/L mCPP)were 3,633 mm,4,280 mm,and 3,894 mm,respectively.This indicates that 200μg/mL of Scutellariae Radix extract can alleviate the anxiety behavior induced by 0.1 nmol/L mCPP in 30-day-old zebrafish.Additionally,the anxiety behavior of the zebrafish conformed to thigmotaxis.Eleven active components of Scutellariae Radix had stronger binding energies with GABAAR compared to the original ligand diazepam(-7.2 kcal/mol),with the strongest being oroxylin A(-8.8 kcal/mol).The main components baicalein,baicalin,wogonin,and wogonoside also showed strong binding energies of-8.3,-7.7,-8.3,and-7.3 kcal/mol,respectively.It is predicted that flavonoids such as baicalin are the primary substances for Scutellariae Radix′s anxiolytic effects.Conclusion:Scutellariae Radix exhibits a definitive anxiolytic effect on zebrafish,and its active mechanism may be related to the activation of GABAAR by flavonoid components of Scutellariae Radix.

关 键 词：黄芩 斑马鱼 焦虑 分子对接 γ-氨基丁酸A型受体 

分 类 号：R285.5[医药卫生—中药学]