Royal Jelly Reduces Cholesterol Levels, Ameliorates Aß Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer's Disease.

ABSTRACT

Alzheimer's disease (AD) is the most common form of dementia characterized by aggregation of amyloid ß (Aß) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aß deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aß toxicity. However, little is known about how RJ regulates Aß formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aß levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aß in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aß immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of ß-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aß levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD.