Oligosaccharides from black ginseng innovatively prepared by low‐temperature steam‐heating process ameliorate cognitive impairment in Alzheimer's disease mice via the Keap‐1/Nrf2 pathway

Abstract BACKGROUND Our objective in this study was to evaluate the effectiveness of oligosaccharides extracted from black ginseng (OSBG), innovatively prepared by a low‐temperature steam‐heating process, in the improvement of learning and memory impairment in mice, as well as the mechanism(s). RESULTS Eight carbohydrates involving isomaltose and maltotetraose were detected in black gensing; monosaccharide residues including mannose and rhamnose were also discovered. OSBG‐treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine group. OSBG could decrease acetylcholinesterase activity in a tissue‐dependent fashion but not in a dose‐dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase, glutathione, glutathione peroxidase (GPx), and Kelch‐like ECH‐associated protein 1, downregulation of malondialdehyde and nuclear factor erythroid 2‐related factor 2 in the tissues. Finally, at the genus level, we observed that the OSBG interventions increased the relative abundance of probiotics (e.g., Barnesiella, Staphylococcus , Clostridium_XlVb ) and decreased pernicious bacteria such as Eisenbergiella and Intestinimonas , compared to the Alzheimer's disease mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine‐induced intestinal microbiota in mice, providing homeostasis of gut microbiota and providing evidence for microbiota‐regulated therapeutic potential. CONCLUSION Our results showed for the first time a clear role for OSBG in improving scopolamine‐induced memory impairment by inhibiting cholinergic dysfunction in a tissue‐dependent manner. Additionally, OSBG administration relieved oxidative stress by activating the Keap‐1/Nrf2 pathway and modulating the gut microbiota. Collectively, OSBG may be a promising target for neuroprotective antioxidants for improving memory and cognition in Alzheimer's disease patients. © 2024 Society of Chemical Industry.