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

Abstract

<i>Astragalus membranaceus</i> is commonly used in traditional Chinese medicine for strengthening the host defense system. <i>Astragalus membranaceus</i>-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 <i>Astragalus membranaceus</i>-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. <i>Astragalus membranaceus</i>-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that <i>Astragalus membranaceus</i>-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. <i>Astragalus membranaceus</i>-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 <i>Astragalus membranaceus</i>-polysaccharides administration. The plaque deposition, however, was not significantly affected by <i>Astragalus membranaceus</i>-polysaccharides administration. These findings suggest that <i>Astragalus membranaceus</i>-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.