Department of Neurology, Jiangsu Traditional Chinese Medicine Hospital, The Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, 210029, China.
Department of Cardiology, Jiangsu Traditional Chinese Medicine Hospital, The Affiliated Hospital of Nanjing University of Traditional Chinese medicine, Nanjing, 210029, China.
Phytother Res. 2018 Jun;32(6):1047-1055. doi: 10.1002/ptr.6043. Epub 2018 Feb 26.
Excessive amyloid beta (Aβ) deposition in brain is mainly responsible for cell damage and blood-brain barrier (BBB) disruption in Alzheimer's disease (AD). Catalpol, an iridoid glucoside extracted from the root of Rehmannia glutinosa Libosch, has neuroprotective effect against AD. It is unclear whether catalpol has a protective effect on Aβ-induced BBB leakage. We employed an immortalized endothelial cell line (bEnd.3) and astrocytes co-culture to mimic a BBB model in vitro and investigated the effect of catalpol on BBB. We found that treatment with catalpol decreased BBB hyperpermeability induced by fibrillar Aβ . Data from western blotting showed that catalpol prevented fibrillar Aβ -induced bEnd.3 cell apoptosis through mitochondria-dependent and death receptor pathways; decreased the levels of matrix metalloproteinases (MMPs), MMP-2, MMP-9, and the receptor for advanced glycation end products; and increased the levels of tight junction proteins (ZO-1, occludin, and claudin-5), low-density lipoprotein receptor-related protein 1, and P-glycoprotein in fibrillar Aβ -treated bEnd.3 cells. Moreover, catalpol also enhanced soluble Aβ efflux across the fibrillar Aβ -treated bEnd.3 cells BBB monolayer model. Altogether, our results suggest that catalpol alleviate fibrillar Aβ -induced BBB disruption, enhance soluble Aβ clearance, and offer a feasible therapeutic application in AD treatment.
脑内过量的淀粉样蛋白 β (Aβ) 沉积主要负责阿尔茨海默病 (AD) 中的细胞损伤和血脑屏障 (BBB) 破坏。梓醇是从地黄的根中提取的环烯醚萜苷，具有抗 AD 的神经保护作用。梓醇是否对 Aβ 诱导的 BBB 渗漏有保护作用尚不清楚。我们采用永生化的内皮细胞系 (bEnd.3) 和星形胶质细胞共培养来体外模拟 BBB 模型，并研究梓醇对 BBB 的作用。我们发现，梓醇处理可降低纤维状 Aβ 诱导的 BBB 通透性增加。Western blot 数据分析表明，梓醇通过线粒体依赖和死亡受体途径预防纤维状 Aβ 诱导的 bEnd.3 细胞凋亡；降低基质金属蛋白酶 (MMPs)、MMP-2、MMP-9 和晚期糖基化终产物受体的水平；增加紧密连接蛋白 (ZO-1、occludin 和 claudin-5)、低密度脂蛋白受体相关蛋白 1 和 P-糖蛋白的水平，在纤维状 Aβ 处理的 bEnd.3 细胞中。此外，梓醇还增强了穿过纤维状 Aβ 处理的 bEnd.3 细胞 BBB 单层模型的可溶性 Aβ 外排。总之，我们的结果表明梓醇减轻纤维状 Aβ 诱导的 BBB 破坏，增强可溶性 Aβ 清除，并为 AD 的治疗提供了可行的治疗应用。
