Kangen-karyu improves memory deficit caused by aging through normalization of neuro-plasticity-related signaling system and VEGF system in the brain

Aim of the study: Kangen-karyu (KK) is a traditional Chinese prescription consisting of six different herbs. This study was conducted to investigate the anti-dementia effect of KK on aging-induced cognitive deficits and the underlying mechanism using senescence-accelerated mice prone (SAMP8). Materials and methods: Twenty-week old SAMP8 (older SAMP8) were used as an animal model of aging and age-matched senescence-resistant inbred strain (SAMR1) and 8-week-old SAMP8 (young SAMP8) were as controls. Older SAMP8 received daily administration of KK (100. mg/kg, p.o.) or water vehicle for 22 days. Results: Compared to the controls, older SAMP8 exhibited cognitive deficits in the object recognition and object location tests; however, KK improved the deficits caused by aging. Moreover, the older SAMP8 treated with vehicle exhibited reduced anxiety-like behavior in the elevated plus-maze test compared to SAMR1, but KK had no effect on emotional disorder of older SAMP8. The levels of biochemical factors related to neuro-plasticity and learning and memory; i.e., phosphorylated forms of N-methyl-d-aspartate receptor 1, Ca²⁺/calmodulin-dependent protein kinase II, and cyclic AMP-responsive element-binding protein, and brain-derived neurotrophic factor, were significantly decreased in older SAMP8 compared to those in the control animals. KK normalized the levels of these factors. Moreover, the mRNA and protein levels of vascular endothelial growth factor (VEGF) and its receptor type 2 in the cerebral cortices of older SAMP8 were down-regulated by aging, but these levels were reversed by KK. Conclusions: These findings suggest that normalization of neuro-plasticity-related neuronal signaling and VEGF systems in the brain may be of the mechanisms underlying the ameliorative effects of KK on the cognitive deficits in older SAMP8.