Protective effect of madecassoside against cognitive impairment induced by D-galactose in mice.

This study was designed to investigate the protective effect of madecassoside from Hydrocotyle sibthorpioides against cognitive impairment induced by D-galactose (D-gal) in mice. The result revealed that treatment with madecassoside significantly reversed D-gal-induced learning and memory impairments, as measured by the Morris water-maze test. Studies on the potential mechanisms of this action showed that madecassoside significantly reduced oxidative stress and suppress inflammatory responses via blocking NF-κB and ERK/p38 MAPK pathways. Moreover, madecassoside markedly attenuated the content and deposition of β-amyloid peptide by inducing a decrease in the expression of amyloid protein precursor, β-site amyloid cleaving enzyme-1 and cathepsin B and an increase in the levels of neprilysin and insulin-degrading enzyme. Madecassoside significantly increased the expression of synapse plasticity-related proteins in the hippocampus, such as postsynaptic density 95, long-term potentiation, N-methyl-D-aspartic acid receptors, Ca(2+)/calmodulin-dependent protein kinase II, NMDA receptor subunit 1, protein kinase C, protein kinase A, cAMP-response element binding protein, and brain-derived neurotrophic factor. In addition, madecassoside significantly increased the levels of acetylcholine but decreased cholinesterase activity. In conclusion, the protective effect of madecassoside against d-gal-induced cognitive impairment was mainly due to its ability to reduce oxidative damage, improve synaptic plasticity and restore cholinergic function. These findings suggest that madecassoside can be considered as a potential agent for preventing cognitive impairment.