Long term administration of loquat (Eriobotrya japonica) leaves and their major component, ursolic acid, attenuated endogenous amyloid-β burden and memory impairment

Loquat (Eriobotrya japonica) leaves exert anti-inflammatory and neuroprotective effects in several animal models of neurodegenerative diseases, including Alzheimer’s disease. Loquat leaves contain many bioactive components such as ursolic acid (UA) and amygdalin. In this study, we investigated the effects of loquat leaf methanol extracts on amyloid-beta peptide (Ab) 42 production in human neuroglioma H4 cells stably expressing the Swedish-type APP695 (APPNL-H4 cells). We also evaluated endogenous Ab42 production, phosphorylated tau (P-tau), and working memory in wild-type C57BL/6J mice fed loquat leaves for 12 months. Surprisingly, the methanol extract of loquat leaves greatly enhanced cellular Ab42 production in APPNL-H4 cells. Administration of loquat leaf powder resulted in increased Ab42 levels after 3 months and decreased levels after 12 months compared to control mice. Administration of loquat leaf powder had no effect on working memory after 3 months, but improved working memory after 12 months. We hypothesized that the major compounds contained in loquat leaves that affect Ab42 production are UA and amygdalin. Administration of UA decreased Ab42 and P-tau levels and improved working memory after 12 months, similar to the administration of loquat leaves for 12 months. Amygdalin enhanced cellular Ab42 production in APPNL-H4 cells, which was the same as the loquat leaf extract. Three-month administration of amygdalin in mice increased Ab42 levels slightly but did not significantly increase them, which is similar to the trend observed with the administration of loquat leaves for 3 months. In this study, we demonstrated that long-term administration of loquat leaves and UA attenuated endogenous Ab42 levels, P-tau, and memory impairment. UA was likely the main compound contained in loquat leaves responsible for the decrease in intracerebral Ab42 and P-tau levels. Our data also suggest that amygdalin might be one of the compounds in loquat leaves responsible for the transiently increased intracerebral Ab42 levels, although this effect did not seem to accelerate neurodegeneration.