刺果番荔枝根提取物改善2型糖尿病药效和作用机制研究  

The anti-diabetic effect and possible mechanism of the Annona muricata L.root extract in type 2 diabetic mice

作　　者：龚晶雯 陈永康[1,2,3,4] 李海龙 李友宾[1,2,3,4] GONG Jing-wen;CHEN Yong-kang;LI Hai-long;LI You-bin(Key Laboratory of Tropical Translational Medicine of Ministry of Education;Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs;Haikou Key Laboratory of Li Nationality Medicine;School of Pharmacy,Hainan Medical University,Haikou 571199,China)

机构地区：[1]教育部热带转化医学重点实验室 [2]海南省热带药用植物研究开发重点实验室 [3]海口市黎族医药重点实验室 [4]海南医学院药学院,海南海口571199

出　　处：《海南医学院学报》2023年第1期8-14,共7页Journal of Hainan Medical University

基　　金：国家自然科学基金项目(No.81460591);海南医学院校培基金(HY2018-09)。

摘　　要：目的:研究刺果番荔枝根提物(AME)对2型糖尿病(T2DM)ICR小鼠的作用效果,探究其作用机制。方法:4周高脂饮食后,给予ICR小鼠口服1 g/kg烟酰胺和120 mg/kg链脲佐菌素(STZ)构建T2DM模型。按照模型组、200 mg/kg二甲双胍组和50、100、200 mg/kg AME组将T2DM鼠随机分为5组,连续给药4周。每周测空腹血糖和体重。实验结束前一周进行口服糖耐量实验(OGTT)并检测糖化血红蛋白(HbA1c)水平。给药结束后血清学检测总胆固醇(TG)、甘油三酯(TC)、低密度脂蛋白水平(LDL-C)和胰岛素水平;计算稳态评估模型HOMA-IR和HOMA-%β。Western blot法检测肝脏中单磷酸腺苷活化蛋白激酶(AMPK)、乙酰辅酶A羧化酶(ACC)、葡萄糖-6-磷酸羧化酶(G6Pase)和磷酸烯醇丙酮酸羧激酶(PCK1)表达量。结果:200 mg/kg AME明显降低了TT2DM小鼠空腹血糖、HbA1c、TG和LDL-C水平;明显降低了HOMA-IR和HOMA-%β指数;降低了OGTT曲线下面积;抑制了ACC和G6Pase蛋白表达水平,并激活了AMPK蛋白表达。结果:AME表现出了对T2DM良好的治疗活性,其机制可能与激活AMPK蛋白,抑制ACC和G6Pase蛋白表达有关。OBJECTIVE:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.METHODS:After 4 weeks of high-fat diet,ICR mice were given 1 g/kg nicotine and 120 mg/kg streptozotocin(STZ)orally to construct a T2DM model.The T2DM mice were randomly divided into five groups:model group,200 mg/kg metformin group and 50,100,200 mg/kg AME groups.Drugs were oral administered continuously for 4 weeks.Fasting blood glucose and body weight were measured weekly.Oral glucose tolerance test(OGTT)and detection of serum glycated hemoglobin(HbA1c)level were performed one week before the end of the experiment.At the end of drug administration,serum total cholesterol(TG),triglycerides(TC),low-density lipoprotein levels(LDL-C)and insulin levels were tested by lipid detection kits;homeostasis model assessment-estimated insulin resistance(HOMA-IR)and HOMA-βindexes were calculated.Liver and kidney tissues were weighed to calculate organ indices and pathological tests were performed.Western blot was performed in the liver to detect adenosine monophosphate-activated protein kinase(AMPK),acetyl coenzyme A carboxylase(ACC),glucose-6-phosphate carboxylase(G6Pase),and phosphoenolpyruvate carboxykinase(PCK1)protein expression.RESULTS:with 200 mg/kg AME significantly reduced fasting blood glucose,HbA1c,TG and LDL-C levels,protected liver and kindey in diabetic mice,decreased the area under the OGTT curve,inhibited ACC and G6Pase protein expressions,and activated AMPK protein expression.CONCLUSION:AME showed good therapeutic activity against T2DM,and the mechanism may be related to the activation of AMPK and inhibition of ACC and G6Pase proteins.

关 键 词：刺果番荔枝 2型糖尿病 AMPK 肝糖异生 

分 类 号：R285.5[医药卫生—中药学]