St. John's Wort Reduces Beta-Amyloid Accumulation in a Double Transgenic Alzheimer's Disease Mouse Model-Role of P-Glycoprotein
St. John's Wort Reduces Beta-Amyloid Accumulation in a Double Transgenic Alzheimer's Disease Mouse Model-Role of P-Glycoprotein
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DOI：
10.1111/bpa.12069
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发表时间：
2014-01-01
期刊：
影响因子：
6.4
通讯作者：
Vogelgesang, Silke
中科院分区：
文献类型：
--
作者：
Brenn, Anja;Grube, Markus;Vogelgesang, Silke
三磷酸腺苷结合盒转运蛋白P-糖蛋白（ABCB 1）参与β-淀粉样蛋白从大脑进入血液的输出，有证据表明，年龄相关的脑P-糖蛋白含量的不足可能参与阿尔茨海默病的发病机制。P-糖蛋白的功能和表达可以被包括贯叶连翘（圣约翰草）提取物在内的多种化合物间接诱导。为了阐明圣约翰草对脑中β-淀粉样蛋白和P-糖蛋白表达的积累的作用，将圣约翰草提取物（最终贯叶金丝桃素浓度5%）分别在60或120天的时间内喂给30日龄雄性C57 BL/6 J-APP/PS1（+/-）小鼠。接受无圣约翰麦芽饮食的雄性C57 BL/6 J-APP/PS1（+/-）小鼠作为对照。接受圣约翰草提取物的小鼠显示（i）实质β-淀粉样蛋白1-40和1-42积累的显著减少;和（ii）脑血管P-糖蛋白表达的中度但统计学显著增加。因此，脑血管P-糖蛋白的诱导可能是一种新的治疗策略，以保护大脑β-淀粉样蛋白的积累，从而阻止阿尔茨海默病的进展。
The adenosine triphosphate-binding cassette transport protein P-glycoprotein (ABCB1) is involved in the export of beta-amyloid from the brain into the blood, and there is evidence that age-associated deficits in cerebral P-glycoprotein content may be involved in Alzheimer's disease pathogenesis. P-glycoprotein function and expression can be pharmacologically induced by a variety of compounds including extracts of Hypericum perforatum (St. John's Wort). To clarify the effect of St. John's Wort on the accumulation of beta-amyloid and P-glycoprotein expression in the brain, St. John's Wort extract (final hyperforin concentration 5%) was fed to 30-day-old male C57BL/6J-APP/PS1(+/-) mice over a period of 60 or 120 days, respectively. Age-matched male C57BL/6J-APP/PS1(+/-) mice receiving a St. John's Wort-free diet served as controls. Mice receiving St. John's Wort extract showed (i) significant reductions of parenchymal beta-amyloid 1-40 and 1-42 accumulation; and (ii) moderate, but statistically significant increases in cerebrovascular P-glycoprotein expression. Thus, the induction of cerebrovascular P-glycoprotein may be a novel therapeutic strategy to protect the brain from beta-amyloid accumulation, and thereby impede the progression of Alzheimer's disease.