Oral Administration of and Ameliorates Amyloid Beta (Aβ)-Induced Cognitive Impairment by Improving Synaptic Function Through Regulation of TLR4/Akt Pathway.

This study investigated the anti-amnesic effects of () MG4247 and () MG4644 in amyloid beta (Aβ)-induced mice. We confirmed that oral administration of MG4247 and MG4644 ameliorated cognitive impairment in Aβ-induced mice using Y-maze, passive avoidance, and Morris water maze tests. Oral administration of MG4247 and MG4644 protected the antioxidant system by regulating superoxide dismutase levels, reduced glutathione levels, and reduced malondialdehyde contents. Similarly, they attenuated mitochondrial function by decreasing mitochondrial reactive oxygen species levels and increasing mitochondrial membrane potential and ATP levels. In addition, they regulated neuroinflammation and neurotoxicity by modulating the Toll-like receptor 4 (TLR4)/protein kinase B (Akt) pathway. As a result, they enhanced synaptic function by regulating acetylcholine contents, acetylcholinesterase activity, and the expression of synaptic-function-related proteins such as AChE, ChAT, SYP, PSD-95, and GAP-43. Furthermore, the administration of MG4247 and MG4644 improved dysbiosis by promoting the growth of beneficial bacteria while suppressing the growth of harmful bacteria. Therefore, these results suggest that MG4247 and MG4644 may be used as probiotics to prevent cognitive impairment.