A Novel Multifunctional Compound Camellikaempferoside B Decreases Aβ Production, Interferes with Aβ Aggregation, and Prohibits Aβ-Mediated Neurotoxicity and Neuroinflammation.

Abstract

Accumulating evidence suggested that soluble oligomeric β-amyloid protein (Aβ) exerts diverse roles in neuronal cell death, neuroinflammation, oxidative stress, and the eventual dementia associated with Alzheimer's disease (AD). Developing an agent with multiple properties may be a reasonable strategy for the treatment of AD. In this study, we isolated a novel multifunctional compound named camellikaempferoside B (YCF-2) from Fuzhuan brick tea. YCF-2 consists of kaempferol backbone, p-coumaric acid (p-CA) group, and a novel structure of rhamnopyranosyl group at the C-4' position, possessing the properties of both kaempferol and p-CA. YCF-2 significantly inhibited Aβ production by decreasing β-secretase activity. Moreover, YCF-2 suppressed Aβ42 fibrillation and facilitated nontoxic oligomer formation by binding to Aβ42 oligomers and by blocking the conformational transition to β-sheet. Furthermore, YCF-2 ameliorated Aβ-induced neuronal cell death, ROS production, inflammatory factor release, and microglia activation by blocking the NF-κB signaling pathway in microglia. These findings indicated that YCF-2 with a novel lead structure has potential applications for drug development for AD treatment.