小檗碱和肉桂多酚联合使用可通过Bas-TGR5-GLP-1改善T2DM大鼠的葡萄糖代谢  

The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1

作　　者：刘万 梁菲 蔡铁全 李莹[1] 李乐[1] 杨树才[1] 刘影[1] 赵妍[1] LIU Wan;LIANG Fei;CAI Tie-quan;LI Ying;LI Le;YANG Shu-cai;LIU Ying;ZHAO Yan(Harbin Medical University,Harbin 150076,China;Food Evaluation Center,State Administration for Market Regulation,Beijing 100070,China)

机构地区：[1]哈尔滨医科大学,黑龙江哈尔滨150076 [2]国家市场监督管理总局食品评价中心,北京100070

出　　处：《药学学报》2024年第1期135-142,共8页Acta Pharmaceutica Sinica

基　　金：哈尔滨医科大学创新基金。

摘　　要：小檗碱(berberine,BBR)是黄连的主要活性成分,有降血糖作用,但由于口服生物利用度低,限制了其临床应用。肉桂(cinnamomum cassia,Cin)中的多酚成分,对2型糖尿病(T2DM)有益。二者联合应用可能会有相加的效果。本研究通过对糖尿病大鼠联合用药干预,探讨二者联合的降血糖作用效果及机制。将造模成功的大鼠随机分为5组[糖尿病对照组(Con)、小檗碱组(BBR)、肉桂多酚组(Cin)、联合组(BBR+Cin)、二甲双胍组(Met)]和正常对照组(Nor)。该动物实验得到了动物伦理委员会的批准(批准号:HMUIRB2022003)。经口给予受试物,对照组给予等体积溶剂,每周称量体重。给药30天后进行口服葡萄糖耐量实验和胰岛素敏感性实验,检测空腹血糖(FBG)、糖化血清蛋白(GSP)、血清胰岛素(INS)水平,采用高通量测序技术检测肠道菌群构成,实时荧光定量PCR(RT-qPCR)和蛋白免疫印迹(Western blot)分别检测肝脏和结肠组织中G蛋白偶联受体5(TGR5)和胰高血糖素样肽-1(GLP-1)的表达。结果显示,与模型对照组比较,联合组大鼠FBG(P<0.01)、GSP(P<0.01)水平降低,胰岛素抵抗改善,效果优于BBR组。联合处理增加了拟杆菌属、普雷沃菌属和乳杆菌属的相对丰度,逆转小檗碱单独诱导组的乳杆菌属减少的结果,且二者联合可促进TGR5和GLP-1的表达。综上,联合应用肉桂多酚和小檗碱比单独应用小檗碱能更好地调节糖代谢。小檗碱联合肉桂多酚可通过改变肠道菌群,增加TGR5和GLP-1蛋白表达,改善2型糖尿病大鼠胰岛β细胞功能,从而更好地调节糖代谢。Berberine(BBR)is the main pharmacological active ingredient of Coptidis,which has hypoglycemic effect,but its clinical application is limited due to its poor oral bioavailability.Polyphenols,derived from cinnamon,are beneficial for type 2 diabetes mellitus(T2DM).The combination of both may have an additive effect.The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats.The modeling rats were randomly divided into 5 groups(berberine group,cinnamon group,combined group,metformin group,diabetic control group)and normal control group.The animal experiments were approved by the Animal Ethics Committee(approval number:HMUIRB2022003).The subjects were given orally,and the control group was given equal volume solvent and body weight was measured weekly.Thirty days after administration,oral glucose tolerance test and insulin sensitivity test were performed,and fasting blood glucose(FBG),glycated serum protein(GSP),and serum insulin(INS)levels were detected;high-throughput sequencing technology was used to detect intestinal microbiota structure;real-time quantitative PCR(RT-qPCR)and Western blot were used to detect G protein-coupled receptor 5(TGR5)and glucagon-like peptide-1(GLP-1)expression levels.The results showed that,compared with the diabetic control group,the levels of FBG(P<0.01)and GSP(P<0.01)in the combined group were lower,and the insulin resistance was improved,which was better than that in the berberine group.Combined treatment increased the relative abundance of Bacteroides,Prevotella and Lactobacillus,reversed the decrease in Lactobacillus in the berberine alone induction group,and the combination of the two could promote the expression of TGR5 and GLP-1.In summary,the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone.Berberine combined with cinnamon can improve the function of pancreatic isletβcells in diabetes mellitus type 2 rats by changing the intestinal microbiota,

关 键 词：小檗碱 肉桂多酚 肠道菌群 2型糖尿病 糖代谢 

分 类 号：R966[医药卫生—药理学]