Microglial Neuroprotective Effects
Abstract
Glycation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), where it potentiates the aggregation and toxicity of proteins such as β-amyloid (Aβ). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models), (4) anti-Aβ aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties. Berry crude extracts (CE) were fractionated to yield anthocyanins-free (ACF) and anthocyanins-enriched (ACE) extracts. The berry ACEs (at 100 μg/mL) showed superior free radical scavenging, reactive carbonyl species trapping, and anti-glycation effects compared to their respective ACFs. The berry ACEs (at 100 μg/mL) inhibited both thermal- and MGO-induced Aβ fibrillation. In addition, the berry ACEs (at 20 μg/mL) reduced H₂O₂-induced reactive oxygen species production, and lipopolysaccharide-induced nitric oxide species in BV-2 microglia as well as decreased H₂O₂-induced cytotoxicity and caspase-3/7 activity in BV-2 microglia. The free radical scavenging, reactive carbonyl trapping, anti-glycation, anti-Aβ fibrillation, and microglial neuroprotective effects of these berry extracts warrant further in vivo studies to evaluate their potential neuroprotective effects against AD.
糖基化与多种神经退行性疾病有关，包括阿尔茨海默病(AD)，它增强了蛋白质的聚集和毒性，如β-淀粉样蛋白(Aβ)。已发表的研究支持几种富含多酚的水果的抗糖基化和神经保护作用，包括浆果，它们富含花青素。以黑莓、黑覆盆子、蓝莓、蔓越莓、红覆盆子和草莓为研究对象，对其提取物进行了以下指标的测定:(1)总酚和花青素含量;(2)清除DPPH自由基的能力;(3)抗糖基化(使用bsa -果糖和BSA-MGO模型)，(4)抗a β聚集(使用热-和MGO诱导的纤维性模型)，(5)小鼠小胶质细胞(BV-2)的神经保护特性。将浆果粗提物(CE)分离得到无花青素(ACF)和富花青素(ACE)两种提取物。在100 μg/mL浓度下，与各自的acf相比，ace具有较好的自由基清除、活性羰基物种捕获和抗糖基化作用。在100 μg/mL浓度下，草莓ace对mgo和热致Aβ纤维均有抑制作用。此外，浆果ACEs (20 μg/mL)降低了BV-2小胶质细胞H₂O₂诱导的活性氧生成和脂多糖诱导的一氧化氮生成，并降低了H₂O₂诱导的BV-2小胶质细胞的细胞毒性和caspase-3/7活性。这些浆果提取物的自由基清除、活性羰基捕获、抗糖基化、抗a β纤维性颤动和小胶质神经保护作用，需要进一步的体内研究来评估它们对AD的潜在神经保护作用。
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