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Many researchers have focused on the oligomeric form of proanthocyanidins with a lower level of polymerization found in foodstuffs such as grape seeds and blackberries. The present study indicated that the oral administration of oligomers isolated from persimmon fruits extended the lifespan of senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence. On the other hand, oligomer-treated SAMP8 did not show stereotypical behavior. We also revealed that the oral administration of oligomers improved spatial and object recognition memory in SAMP8. The density of axons in the hippocampal CA1 was significantly increased by oligomer administration. Moreover, the administration of oligomers increased the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in the hippocampal CA3, hypothalamus, and choroid plexus. We speculate that memory improvement accompanied by histological changes may be induced directly in the hippocampus and indirectly in the hypothalamus and choroid plexus through VEGFR-2 signaling. In the present study, we elucidated the protective effect of oligomers against memory impairment with aging. VEGFR-2 signaling may provide a new insight into ways to protect against memory deficit in the aging brain.

Role of Oligomeric Proanthocyanidins Derived from an Extract of Persimmon Fruits in the Oxidative Stress-Related Aging Process