2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione Ameliorates Diabetic Cognitive Impairment Through Inhibiting Hif3α and Apoptosis.
2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione Ameliorates Diabetic Cognitive Impairment Through Inhibiting Hif3α and Apoptosis.
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2-Dodecyl-6-Methoxycyclohexa-2，5-Diene-1，4-Dione通过抑制Hif3α和细胞凋亡改善糖尿病认知功能障碍
DOI：
10.3389/fphar.2021.708141
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zou C
中科院分区：
文献类型：
--
作者：
Wang L;Cao J;Xu Q;Lu X;Yang X;Song Q;Chen S;Du K;Huang R;Zou C
糖尿病（DM）是认知障碍的独立危险因素。虽然糖尿病认知功能障碍的病因复杂且多因素，但海马神经元凋亡被认为是糖尿病所致认知功能障碍的主要原因。2-十二烷基-6-甲氧基环己-2,5-二烯-1,4-二酮（DMDD）是从杨桃Averrhoa carambola . L.的根中纯化出来的，先前的研究表明DMDD对延缓糖尿病的一些并发症是安全有效的。然而，DMDD改善2型糖尿病小鼠糖尿病认知功能障碍的疗效尚未见报道。本研究采用Y迷宫法和新物体识别法对db/db小鼠进行行为评价。采用小鼠lncRNA微阵列分析方法检测db/db小鼠海马区基因表达谱。通过Western blotting检测db/db小鼠和高糖处理的HT22细胞中神经变性相关蛋白和凋亡相关蛋白的变化。我们观察到，DMDD治疗显著改善了db/db小鼠的空间工作记忆和物体识别记忆障碍。进一步的研究表明，DMDD治疗后，db/db小鼠海马区神经变性相关蛋白tau减少。DMDD处理后，db/db小鼠海马组织中11种lncrna和包括促凋亡基因Hif3a在内的4种mrna的表达显著不同。与db/m对照组相比，糖尿病db/db小鼠海马组织中Hif3a、cleaved parp和caspase 3蛋白的表达显著升高，DMDD治疗后表达降低。DMDD在hg处理的HT22细胞中也观察到类似的有益作用。这些数据表明，DMDD通过降低促凋亡蛋白Hif3a的表达，抑制神经元凋亡，从而减轻认知功能障碍。总之，我们的研究表明，DMDD有很大的潜力成为一种新的预防和治疗糖尿病认知障碍的化合物。
Diabetes mellitus (DM) is an independent risk factor for cognitive impairment. Although the etiology of diabetic cognitive impairment is complex and multifactorial, the hippocampus neuronal apoptosis is recognized as a main cause of diabetes-induced cognitive impairment. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was purified from the roots of Averrhoa carambola L. Previous research demonstrated that DMDD was safe and effective in delaying some diabetic complications. However, the efficacy of DMDD to ameliorate diabetic cognitive impairment in type 2 diabetes mice has not been reported. In the present study, the behavioral evaluation was performed by Y maze and novel object recognition in db/db mice. Gene expression profiles were detected using mouse lncRNA microarray analysis in the hippocampi of db/db mice. Changes in the neurodegeneration-associated proteins and the apoptosis-related proteins were determined in both db/db mice and high glucose-treated HT22 cells by Western blotting. We observed that DMDD treatment significantly ameliorated the spatial working memory and object recognition memory impairment in db/db mice. Further study showed that neurodegeneration-associated protein tau was decreased after DMDD treatment in the hippocampi of db/db mice. Eleven lncRNAs and four mRNAs including pro-apoptotic gene Hif3a were significantly differently expressed after DMDD treatment in the hippocampi of db/db mice. The expression of Hif3a, cleaved parp, and caspase 3 proteins was significantly increased in the hippocampi of diabetic db/db mice compared with db/m control mice and then decreased after DMDD treatment. Similar beneficial effects of DMDD were observed in HG-treated HT22 cells. These data indicate that DMDD can alleviate cognitive impairment by inhibiting neuronal apoptosis through decreasing the expression of pro-apoptotic protein Hif3a. In conclusion, our study suggests that DMDD has great potential to be a new preventive and therapeutic compound for diabetic cognitive impairment.
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影响因子：
6
作者：
García-García VA;Alameda JP;Page A;Casanova ML
通讯作者：
Casanova ML
DOI：
10.1007/978-1-4939-8994-2_10
发表时间：
2019-01-01
期刊：
PRE-CLINICAL MODELS
影响因子：
--
作者：
Kraeuter, Ann-Katrin;Guest, Paul C.;Sarnyai, Zoltan
通讯作者：
Sarnyai, Zoltan
从杨桃根中分离出的 2-十二烷基-6-甲氧基环己-2,5-二烯-1,4-二酮通过抑制 TLR4/MyD88/NF-kappa B 通路改善糖尿病肾病
DOI：
10.2147/dmso.s209436
发表时间：
2019-01-01
期刊：
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
影响因子：
--
作者：
Lu, Shunyu;Zhang, Hongliang;Huang, Renbin
通讯作者：
Huang, Renbin
影响因子：
4.3
作者：
Ola, Mohammad Shamsul;Nawaz, Mohd;Ahsan, Haseeb
通讯作者：
Ahsan, Haseeb
影响因子：
9.9
作者：
Pagano, Gennaro;Polychronis, Sotirios;Politis, Marios
通讯作者：
Politis, Marios