A novel compound AB-38b improves diabetes-associated cognitive decline in mice via activation of Nrf2/ARE pathway
| Autor: | Yue Liu, Zhuang-Zhuang Tang, Yao-Wu Liu, Teng-Fei Ma, Lei Du, Ya-Jing Chen, Qian Lu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Glycation End Products
Advanced Male 0301 basic medicine medicine.medical_specialty NF-E2-Related Factor 2 Resveratrol medicine.disease_cause Hippocampus Antioxidants Streptozocin Diabetes Mellitus Experimental RAGE (receptor) Diabetes Complications Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glycation Internal medicine Diabetes mellitus Diabetes Mellitus medicine Animals Cognitive Dysfunction Phosphorylation Cognitive decline Receptor Neurons Chemistry General Neuroscience Biphenyl Compounds Ketones Streptozotocin medicine.disease Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology 030217 neurology & neurosurgery Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Brain Research Bulletin. 150:160-167 |
| ISSN: | 0361-9230 |
| DOI: | 10.1016/j.brainresbull.2019.05.010 |
| Popis: | Objective Diabetes-associated cognitive decline (DACD) is increasingly being concerned, and oxidative stress plays a vital role in the pathological process. AB-38b is a novel synthetic compound with two specific active groups of biphenyl dicarboxylate and α, β unsaturated ketone, showing good antioxidant activity. The aim of this study was to investigate the ameliorative effects of AB-38b on DACD in mice, and to explore the possible mechanisms from glyoxylase 1 (Glo-1) enhancement and NF-E2-related factor-2 (Nrf2) activation. Methods Experimental type 2 mouse model of diabetes with C57BL/6 mice was made through high-fat diet combining with intraperitoneal streptozotocin. Diabetic mice were treated by gavage with AB-38b (0, 10, 20 and 40 mg/kg) or resveratrol (40 mg/kg), a typical inducer of Nrf2, for 8 weeks. Cognitive performances were evaluated by the novel object recognition task. Then brain tissues were collected to assess hippocampal damages, protein glycation, Glo-1 functions and protein expression, and the classic Nrf2/ARE pathway. Result AB-38b markedly increased the preference index to novel object and the number of neurons in hippocampal CA1 area of diabetic mice. AB-38b significantly elevated the activity and protein of Glo-1, while reduced the levels of advanced glycation end products (AGEs) and protein expression of its receptor RAGE. Moreover, AB-38b raised Nrf2 expression and phosphorylation, as well as the protein expression and enzymatic activity of γ-glutamylcysteine synthetase, a well-known gene of Nrf2/ARE pathway, in hippocampus of the diabetic mice. Conclusion AB-38b improved the cognitive performances of diabetic mice, which was achieved via up-regulation of Glo-1 and activation of Nrf2/ARE pathway. |
| Databáze: | OpenAIRE |
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