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


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, Ca(2+)/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.
Zhao
Qi
Q
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Japan.
Yokozawa
Takako
T
Yamabe
Noriko
N
Tsuneyama
Koichi
K
Li
Xiaohan
X
Matsumoto
Kinzo
K
D000375:Aging / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D019684:Magnoliopsida; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009473:Neuronal Plasticity / Q000187:drug effects*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004365:Drugs, Chinese Herbal; C468270:Kangen-karyu; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium