机译
在5xFAD的阿尔茨海默氏病小鼠模型中,固态脂质姜黄素颗粒比姜黄素具有更好的抗淀粉样蛋白,抗炎和神经保护作用
摘要:BackgroundNeuroinflammation and the presence of amyloid beta protein (Aβ) and neurofibrillary tangles are key pathologies in Alzheimer’s disease (AD). As a potent anti-amyloid and anti-inflammatory natural polyphenol, curcumin (Cur) could be potential therapies for AD. Unfortunately, poor solubility, instability in physiological fluids, and low bioavailability limit its clinical utility. Recently, different lipid modifications in the formulae of Cur have been developed that would enhance its therapeutic potential. For example, we have reported greater permeability and neuroprotection with solid lipid curcumin particles (SLCP) than with natural Cur in an in vitro model of AD. In the present study, we compared the Aβ aggregation inhibition, anti-amyloid, anti-inflammatory responses of Cur and or SLCP in both in vitro and in vivo models of AD. One-year-old 5xFAD-and age-matched wild-type mice were given intraperitoneal injections of Cur or SLCP (50 mg/kg body weight) for 2- or 5-days. Levels of Aβ aggregation, including oligomers and fibril formation, were assessed by dot blot assay, while Aβ plaque load and neuronal morphology in the pre-frontal cortex (PFC) and hippocampus were assayed by immunolabeling with Aβ-specific antibody and cresyl violet staining, respectively. In addition, neuroinflammation was assessed the immunoreactivity (IR) of activated astrocytes (GFAP) and microglia (Iba-1) in different brain areas. Finally, comparisons of solubility and permeability of Cur and SLCP were made in cultured N2a cells and in primary hippocampal neurons derived from E16 pups of 5xFAD mice.