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黄芪多糖改善代谢应激 APPswe/PS1dE9 小鼠的肥胖、肝脂肪变性、神经炎症和认知障碍,而不影响淀粉样蛋白沉积。

Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice.

机构信息

Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei 11220, Taiwan.

Program in Molecular Medicine, School of Life Sciences, National Yang-Ming University, Taipei 11221, Taiwan.

出版信息

Int J Mol Sci. 2017 Dec 18;18(12):2746. doi: 10.3390/ijms18122746.

Abstract

is commonly used in traditional Chinese medicine for strengthening the host defense system. -polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of -polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer's disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. -polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that -polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. -polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by -polysaccharides administration. The plaque deposition, however, was not significantly affected by -polysaccharides administration. These findings suggest that -polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.

摘要
  • 多糖是一种有效的成分,具有多种重要的生物活性,如免疫调节、抗氧化、抗糖尿病、抗炎和神经保护。在本研究中,我们确定了 - 多糖对代谢应激转基因小鼠的影响,以便开发这种大分子用于治疗散发性阿尔茨海默病,一种具有代谢危险因素的神经退行性疾病。

  • 10 周龄的转基因小鼠在出现老年斑之前,接受高脂肪饮食和低剂量链脲佐菌素注射的联合治疗,以建立代谢应激小鼠模型。从 14 周龄开始,- 多糖给药 7 周。

  • 我们发现 - 多糖可降低代谢应激引起的体重、胰岛素和胰岛素和瘦素水平、胰岛素抵抗以及肝甘油三酯增加。- 多糖还改善了代谢应激加重的口服葡萄糖耐量,尽管空腹血糖仅暂时降低。

  • 在大脑中,- 多糖给药还减轻了斑块附近代谢应激引起的星形胶质细胞增生和小胶质细胞活化。然而,斑块沉积并没有被 - 多糖给药显著影响。

  • 这些发现表明,- 多糖可能用于改善代谢应激引起的糖尿病和随后的神经炎症,从而改善代谢应激转基因小鼠的行为表现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b41/5751345/7a42b97f25e8/ijms-18-02746-g001.jpg

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