Department of Neuropathology, Institute of Pathology, University of Greifswald, Greifswald, Germany.
Brain Pathol. 2014 Jan;24(1):18-24. doi: 10.1111/bpa.12069. Epub 2013 Jun 28.
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.
三磷酸腺苷结合盒转运蛋白 P-糖蛋白（ABCB1）参与β-淀粉样蛋白从脑内向血液的输出，有证据表明，与年龄相关的脑 P-糖蛋白含量的减少可能与阿尔茨海默病的发病机制有关。P-糖蛋白的功能和表达可以被多种化合物诱导，包括贯叶金丝桃（圣约翰草）的提取物。为了阐明圣约翰草对脑内β-淀粉样蛋白积累和 P-糖蛋白表达的影响，分别用含有终浓度为 5%贯叶金丝桃素的圣约翰草提取物喂养 30 日龄雄性 C57BL/6J-APP/PS1（+/-）小鼠 60 天或 120 天。年龄匹配的接受不含圣约翰草提取物饮食的 C57BL/6J-APP/PS1（+/-）雄性小鼠作为对照。接受圣约翰草提取物的小鼠表现出：（i）脑实质β-淀粉样蛋白 1-40 和 1-42 积累显著减少；（ii）脑血管 P-糖蛋白表达适度但统计学上显著增加。因此，诱导脑血管 P-糖蛋白可能是一种保护大脑免受β-淀粉样蛋白积累的新的治疗策略，从而阻止阿尔茨海默病的进展。
