Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes
| Autor: | Ling-Shan Gou, Ting Zheng, Teng-Fei Ma, Yao-Wu Liu, Yu-Meng Zhang, Pan-Pan Gu, Ting-Ting Huang |
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| Rok vydání: | 2021 |
| Předmět: |
Encephalopathy
Pharmaceutical Science Hippocampus Morris water navigation task tau Proteins Pharmacology Neuroprotection Cell Line Diabetes Mellitus Experimental Alzheimer Disease Diabetes mellitus Drug Discovery medicine Spirostans Animals Aspartic Acid Endopeptidases Phosphorylation Protein kinase B Brain Diseases Amyloid beta-Peptides Glycogen Synthase Kinase 3 beta Chemistry Neurogenesis medicine.disease Rats PPAR gamma medicine.anatomical_structure Complementary and alternative medicine Cerebral cortex Molecular Medicine Amyloid Precursor Protein Secretases |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 91 |
| ISSN: | 1618-095X |
| Popis: | Background A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. Purpose This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. Methods Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aβ production pathway and tau phosphorylation kinase cascade were examined in these two models. Results Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aβ overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3β cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aβ overproduction was prior to tau hyperphosphorylation in neurons. Conclusion Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aβ overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders. |
| Databáze: | OpenAIRE |
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