白芷在斑马鱼中的降血糖作用及分子对接研究  

Blood Sugar-Reducing Effect of Angelica dahurica Radix on Zebrafish and Its Molecular Docking Study

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作  者:赵康琦 金爱静 王晓月 王艳 宋美营 汤建 闻崇炜[2] ZHAO Kangqi;JIN Aijing;WANG Xiaoyue;WANG Yan;SONG Meiying;TANG Jian;WEN Chongwei(School of Chinese Materia Medica,Bozhou University,Bozhou 236800,China;School of Pharmacy,Jiangsu University,Zhenjiang 212013,China)

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

出  处:《中医药信息》2023年第6期32-37,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(KJ2019ZD80);安徽省大学生创新创业训练计划项目(20221292681);亳州学院科研项目(BYP2021Z01)。

摘  要:目的:初步确定白芷对斑马鱼的降糖作用,并通过分子对接分析其降血糖作用的主要活性成分和关键的结合蛋白。方法:1%葡萄糖诱导6月龄雄性斑马鱼建立高糖模型,以二甲双胍(5 mg/L)为阳性对照药,白芷75%乙醇提物低剂量组(含生药量66 mg/L)和高剂量组(含生药量200 mg/L),连续给药7 d,断尾测血糖。分子对接中以白芷中含量较高的欧前胡素(1)、异欧前胡素(2)等16个化合物为配体,蛋白酪氨酸磷酸酶-1B(PTP1B)等6个蛋白为受体,采用AutoDock Vina软件进行对接,依据结合能虚拟筛选白芷中降血糖活性成分并初步确定降糖关键蛋白。结果:白芷有明显的降斑马鱼高血糖作用,低剂量组和高剂量组斑马鱼的血糖值较模型组分别降低了27.1%和41.2%。分子对接中香豆素类化合物1~5和9、倍半萜类化合物10的结合能较化合物11~16更高,其中氧化前胡素(4)与醛糖还原酶(AR)的结合力最强,结合能为-9.2 kcal/mol,欧前胡素(1)、珊瑚菜素(3)、白当归脑(6)与AR间的结合能也较高,均超过-9.0 kcal/mol。异欧前胡素(2)、水合氧化前胡素(5)与过氧化酶增殖受体(PPARγ)、二肽基肽酶-Ⅳ(DPP-Ⅳ)和PTP1B的结合能力也较强,均超过-7.5 kcal/mol。结论:白芷具有降血糖作用,其主要物质基础可能是香豆素类成分;蛋白AR、PPARγ、PTP1B、DPP-Ⅳ是其潜在的作用靶点。Objective:To determine the blood sugar-reducing effect of Angelica dahurica Radix(ADR),and to analyze the main bioactive components and target proteins of its blood sugar-reducing effect based on molecular docking.Methods:A hyperglycemic model of six month male zebrafish was established by exposing to 1%glucose solution,then administrated with Metformin(5 mg/L),low-dose of ADR(equal to 66 mg/L herbs)and high-dose ADR(equal to 200 mg/L herbs)for another 7 days.The tail was cut and blood-glucose readings were taken by a glucometer.16 compounds like imperatorin(1)and isoimperatorin(2)were chosen as ligands,and 6 proteins including protein tyrosine phosphatase-1B(PTP1B)were selected as receptors.The 16 compounds were docked with receptors separately via software AutoDock Vina,and the hypoglycemic active components of ADR and the target proteins were virtually screened according to the scores.Results:Low-dose and high-dose ADR decreased the blood glucose level by 27.1%and 41.2%compared to the model group.Coumarins 1~5 and 9,as well as sesquiterpene 10 had higher binding affinity than compounds 11~16;among them,oxypeucedanin(4)had the strongest affinity of-9.2 kcal/mol to aldose reductase(AR);imperatorin(1),phellopterin(3)and byakangelicol(6)also had high affinity above-9.0 kcal/mol to AR;isoimperatorin(2)and oxypeucedaninhydrate(5)had high affinity above-8.4 kcal/mol to peroxisome proliferator-activated receptorγ(PPARγ),dipeptidyl peptidase-Ⅳ(DPP-Ⅳ)and PTP1B.Conclusion:ADR had an obvious blood sugar-reducing effect on zebrafish,probably based on the contained coumarins.AR,PPARγ,PTP1B and DPP-Ⅳwere sensitive to coumarins in ADR as potential targets.

关 键 词:白芷 降血糖 分子对接 香豆素 醛糖还原酶 

分 类 号:R285.5[医药卫生—中药学]

 

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