Wine‐Processed <i>Polygonatum cyrtonema Hua</i> Polysaccharides Alleviating Cognitive Dysfunction in <scp>CUMS</scp> Mice by Regulating Intestinal Microbiota

The incidence rate of cognitive dysfunction (CD) urgently requires the development of safe and effective dietary supplements to prevent and treat this disease. <i>Polygonatum cyrtonema Hua</i> (PS) is a traditional Chinese herb that can be used as both food and a medicine, and is known to improve memory and nourish the nerves. However, there has been limited research on the commonly used wine-processed form of PS (WPS) in clinical practice; consequently, we know little about the pharmacological effects of WPS and the mechanisms involved. In this study, we investigated the homogeneous polysaccharides extracted from PS (SP3) and WPS (JP3) and investigated the effects of JP3 on the CD and the brain-gut axis in chronic unpredictable mild stress (CUMS) mice. SP3 and JP3 showed significant differences in terms of molecular weight, monosaccharide content, and surface morphology. Mechanistic studies showed that JP3 affected the brain-gut axis by regulating the gut microbiota and the intestinal barrier, and improved lesions and oxidative stress in the hippocampus, thus alleviating cognitive impairment. JP3 was able to increase probiotics such as <i>Lactobacillus murinus</i>, improve hippocampal lesions, and oxidative stress levels. Compared with inulin, JP3 better promotes the proliferation of <i>Lactobacillus murinus</i> and the production of butyric acid and isobutyric acid. The results suggest that WPS homogeneous polysaccharides can regulate intestinal microbiota and improve cognitive level, which is a potential functional product for the prevention of CD.