Combination of Rare Sugars L-arabinose, D-mannose, D-xylose, D-allulose, and D-tagatose Alleviates Cognitive Impairment in Mice with Type 2 Diabetes Mellitus.

Herein, the study was conducted to elucidate the impact of a rare sugar complex (RSC) containing L-arabinose, D-mannose, D-xylose, D-allulose, and D-tagatose on cognitive impairment in a Type 2 diabetes mellitus (T2DM) mouse model. Specifically, a diabetes model was established by administering a high-fat diet (HFD) followed by streptozotocin injection. Behavioral performance in T2DM mice was assessed using multiple behavioral tests, including the Morris water maze, Y maze, novel object recognition test, and novel location recognition test. Neuronal damage in the hippocampal region was detected through hematoxylin and eosin staining. Superoxide dismutase (SOD) and malondialdehyde (MDA) constituted key biomarkers for assessing oxidative stress, with SOD indicating antioxidant capacity and MDA reflecting lipid peroxidation. Both were quantified via enzyme-linked immunosorbent assay. Additionally, the types and richness of microorganisms in the feces of each group of mice were analyzed through 16S sequencing of gut microbiota. Behavioral assays demonstrated that T2DM mice exhibited learning and memory impairments, which were notably mitigated by the administration of RSC. SOD activity decreased significantly, whereas MDA levels increased substantially. HE staining revealed that RSC effectively suppressed hippocampal cell apoptosis in T2DM mice. Furthermore, RSC treatment restored the diversity and abundance of gut microbiota in T2DM mice. Collectively, these findings suggest that RSC alleviates cognitive impairment in T2DM mice by reducing cerebral oxidative stress and modulating the intestinal microbiome composition.