Xu_2024_J.Sci.Food.Agric__

BACKGROUND: Our objective in this study is to evaluate the effectiveness of the oligosaccharides extracted from black ginseng (BG), 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: 8 carbohydrates involving isomaltose and maltotetraose were detected in BG, where the monosaccharide residues including mannose and rhamnose were discovered too. OSBG-treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine (SCO) group. OSBG could decrease acetylcholinesterase (AChE) activity in a tissue-dependent fashion but not in a dose-dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and Kelch-like ECH-associated protein 1 (Keap1), downregulation of malondialdehyde (MDA) and nuclear factor erythroid 2-related factor 2 (Nrf2) 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 AD mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine-induced intestinal microbiota in mice, providing a homeostasis of gut microbiota and providing evidence for microbiota-regulated therapeutic potentials of it. 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 AD patients. This article is protected by copyright. All rights reserved.