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Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes.
Zhang, Yu-Meng; Zheng, Ting; Huang, Ting-Ting; Gu, Pan-Pan; Gou, Ling-Shan; Ma, Teng-Fei; Liu, Yao-Wu.
Afiliación
  • Zhang YM; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
  • Zheng T; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
  • Huang TT; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
  • Gu PP; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
  • Gou LS; Center for Genetic Medicine, Xuzhou Maternity and Child Health Care Hospital, Xuzhou 221009, Jiangsu, China.
  • Ma TF; Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
  • Liu YW; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Department of Pharmacology, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. Electronic address: ywliu@xzhmu.edu.cn.
Phytomedicine ; 91: 153686, 2021 Oct.
Article en En | MEDLINE | ID: mdl-34333330
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. Aß 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 Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß 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 Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Espirostanos / Encefalopatías / Diabetes Mellitus Experimental / Enfermedad de Alzheimer Límite: Animals Idioma: En Revista: Phytomedicine Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Espirostanos / Encefalopatías / Diabetes Mellitus Experimental / Enfermedad de Alzheimer Límite: Animals Idioma: En Revista: Phytomedicine Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania