Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice
Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice
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DOI：
10.1038/s41401-019-0257-1
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发表时间：
2019-06
影响因子：
8.2
通讯作者：
Hongying Wang;Min Wu;Jun-ling Diao;Jibin Li;Yu-xiang Sun;Xiao Xiao-Xiao
中科院分区：
文献类型：
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作者：
Hongying Wang;Min Wu;Jun-ling Diao;Jibin Li;Yu-xiang Sun;Xiao Xiao-Xiao
2型糖尿病(T2D)和阿尔茨海默病(AD)有几个共同的病理生理特征。石杉碱甲(Huperzine A，Hup A)是从中草药石杉中提取的石杉生物碱，是一种特异性、可逆性的乙酰胆碱酯酶抑制剂，临床上用于治疗AD。在这项研究中，我们研究了Hup A是否改善了高脂诱导(HFD)肥胖小鼠和Geneticob/obb小鼠的代谢和认知功能。Hup A(0.1，0.3 mg · kg−1· d−1，ig)治疗3个月。监测体重并进行糖耐量试验。采用新颖物体再认实验和Morris水迷宫实验评价认知功能。结果发现，Hup A对肥胖小鼠的外周代谢无明显影响，而Hup A(0.1 mg · kg−1· d−1)对高脂饲料喂养小鼠的物体识别和空间记忆能力均有改善作用，但对inob/obb小鼠无明显影响。此外，Hup A治疗显著上调了高脂饲料喂养的小鼠大脑皮质中胰岛素和磷酸化Akt的水平，但不包括NOTOB/OB小鼠。此外，Hup A(0.3，mg · kg−1· d−1)可显著降低皮层β分泌酶(BACE1)的表达。这些结果表明，Hup A(0.1mg. · kg−1· d−1)治疗能有效地改善认知功能，至少在饮食诱导的肥胖小鼠是这样。
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 mossHuperzia 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 geneticob/obmice. HFD andob/obmice 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 inob/obmice. Furthermore, Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice, but notob/obmice. In addition, Hup A (0.3, mg · kg−1· d−1) significantly decreased cortical β-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.