Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats
单位：[1]Institute of Integrated Traditional Chinese and Western Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,华中科技大学同济医学院附属同济医院中西医结合研究所[2]Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China[3]Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China[4]Department of Integrated Traditional Chinese and Western Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China[5]Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, China中医科综合医疗科中西医结合科
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor A beta 42 which was the marker of Alzheimer's disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues. For better understanding the effects of BBr on cognitive action in diabetics, we investigated the functions of BBr involved in anti-inflammation and ameliorating insulin resistance in prefrontal cortex of diabetic rats. Methods: Intragastric administration of BBr (187.5 mg/Kg/d) was used in diabetic rats. Fear-condition assay was applied for cognitive assessment, and relative protein expressions were detected by western-blot. The glucose uptake in prefrontal cortex of diabetic rats was tested by Positron-Emission Tomography imaging. The levels of inflammation mediators were determined by commercial ELISA kits. Results: The inflammation mediator release and insulin resistance in the mPFC of diabetic rats was inhibited by BBr. The activation of PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKC eta and PKC epsilon and the translocation of NF-kB in neuron were also down-regulated by BBr; furthermore, the neuron specific glucose transporter GLUT3 was remarkably augmented by 2-3 times when compared with diabetic group; meanwhile, BBr also promoted glucose uptake in the brain. Additionally BBr decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric A beta 42. Finally, it accelerates the reinforcement of the information and ameliorates cognitive impairment. Conclusion: BBr inhibited the activation of inflammation pathway and insulin resistance in the mPFC of diabetic rats. Finally, it improved the lesion of cognition in diabetic rats.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81573785, 81373872, 31171027, 81371416, 31670778]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [HUST: 2016YXMS191, 2014YGYL005]
第一作者单位：[1]Institute of Integrated Traditional Chinese and Western Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,[2]Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
通讯作者：
推荐引用方式(GB/T 7714)：
chen qingjie,mo ran,wu ninghua,et al.Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats[J].FRONTIERS IN PHARMACOLOGY.2017,8:doi:10.3389/fphar.2017.00334.
APA：
chen,qingjie,mo,ran,wu,ninghua,zou,xin,shi,cai...&chen,juan.(2017).Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats.FRONTIERS IN PHARMACOLOGY,8,
MLA：
chen,qingjie,et al."Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats".FRONTIERS IN PHARMACOLOGY 8.(2017)
