虾青素可以减轻神经炎症提高小鼠记忆力，
或可成为阿尔兹海默症的治疗剂
【文献解读】
虾青素，是一种酮式类胡萝卜素，具有有效的抗氧化剂，抗炎和神经保护性能。神经炎炎症和氧化应激在阿尔茨海默病（AD）的发病机制和发育中是显著的。2019年2月，一篇发表在期刊《Marine Drugs》上的文章，探究了虾青素是否可以减轻脂多糖（LPS）给药的小鼠模型中的神经炎症，氧化应激和记忆损失。
本研究中以小鼠为模式生物并将其随机分为以下四组（n = 8 /组）：对照组、LPS组、虾青素30mg / kg组、虾青素 50 mg / kg组。然后测量大脑中的A-β水平、进行水迷宫和被动避免测试和免疫组化检测胶质纤维酸性蛋白。结果表明，虾青素下调了LPS诱导小鼠脑中的β淀粉样蛋白（A-β）负担，与对照组小鼠的大脑相比，在LPS注入的小鼠的大脑中增加了β-分泌酶的活性，但在虾青素施用的小鼠的大脑中降低；虾青素减轻了小鼠的LPS诱导的记忆障碍；虾青素还可防止小鼠脑中的LPS诱导的神经炎症，给予虾青素的小鼠的胶质纤维酸性蛋白和IBA-1反应细胞数低于LPS注射的小鼠，远高于对照组小鼠。
注：虾青素对脂多糖诱导的小鼠脑内神经炎症和淀粉样蛋白生成的影响。(A)胶质纤维酸性蛋白(GFAP)、IBA-1的免疫组织化学分析 (B)用特异性一抗和生物素标记的二抗在小鼠海马20µm厚的切片上观察了iNOS和COX-2抗体的两个不同区域 (C)用免疫印迹法检测小鼠脑内GFAP、IBA-1、iNOS和COX-2的表达。
综上所述，虾青素通过抑制STAT3活性对脂多糖诱导的小鼠AD模型具有保护作用，而STAT3活性可能通过抗氧化和抗神经炎作用而抑制A-β分泌酶活性，从而抑制A-β的蓄积。本研究为虾青素后续投入治疗阿尔兹海默症的临床试验奠定了基础。
【文献节选】
Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally , we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1–42generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity , neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding.
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