Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice  

作　　者：Hong-ying Wang Min Wu Jun-ling Diao Ji-bin Li Yu-xiang Sun Xiao-qiu Xiao 

机构地区：[1]Department of Endocrinology,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [3]Ministry of Education Key Laboratory of Child Development and Disorders,Children’s Hospital,Chongqing Medical University,Chongqing 400032,China [4]Department of Nutrition and Food Science,Texas A&M University,College Station,TX 77843,USA [5]School of Public Health and Management,Chongqing Medical University,Research Center for Medicine and Social Development,Innovation Center for Social Risk Governance in Health,Chongqing 400016,China

出　　处：《Acta Pharmacologica Sinica》2020年第2期145-153,共9页中国药理学报（英文版）

基　　金：the National Natural Science Foundation of China(81871222,81570763,and 81270947 to XQX);the Fundamental Science and Advanced Technology Research of Chongqing(Major Project,CSTC2015jcyjB0146);the National Program on Key Basic Research Project of China(973 Program,2012CB517505,to XQX).

摘　　要：Type 2 diabetes(T2D)and Alzheimer’s disease(AD)share several common pathophysiological features.Huperzine A(Hup A),a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata,is a specific and reversible inhibitor of acetylcholinesterase,which is clinically used for the treatment of AD.In this study,we investigated whether Hup A improved the metabolic and cognitive functions in the high fat-induced(HFD)obese mice and genetic ob/ob mice.HFD and ob/ob mice were treated with Hup A(0.1,0.3 mg·kg^?1·d^?1,ig)for 3 months.Body weight was monitored and glucose tolerance tests were performed.Novel object recognition test and Morris water maze assay were conducted to evaluate the cognitive functions.We found that the Hup A treatment had no significant effect on peripheral metabolism of obese mice,whereas Hup A(0.1,mg·kg^?1·d^?1)improved both the abilities of object recognition and spatial memory in HFD-fed mice,but not in ob/ob mice.Furthermore,Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice,but not ob/ob mice.In addition,Hup A(0.3,mg·kg^?1·d^?1)significantly decreased corticalβ-secretase(BACE1)expression.In conclusion,these results demonstrate that treatment with Hup A(0.1,mg·kg^?1·d^?1)can effectively improve the cognitive functions,at least in diet-induced obese mice.

关 键 词：OBESITY huperzine A cognitive dysfunction neuronal insulin signaling 

分 类 号：R589.2[医药卫生—内分泌]