Cognitive Clarity Inc., Edmonds, WA, USA.
ProteoTech Inc., Kirkland, WA, USA.
Sci Rep. 2019 Feb 6;9(1):561. doi: 10.1038/s41598-019-38645-0.
Brain aging and Alzheimer's disease both demonstrate the accumulation of beta-amyloid protein containing "plaques" and tau protein containing "tangles" that contribute to accelerated memory loss and cognitive decline. In the present investigation we identified a specific plant extract and its constituents as a potential alternative natural solution for preventing and reducing both brain "plaques and tangles". PTI-00703 cat's claw (Uncaria tomentosa from a specific Peruvian source), a specific and natural plant extract from the Amazon rain forest, was identified as a potent inhibitor and reducer of both beta-amyloid fibrils (the main component of "plaques") and tau protein paired helical filaments/fibrils (the main component of "tangles"). PTI-00703 cat's claw demonstrated both the ability to prevent formation/aggregation and disaggregate preformed Aβ fibrils (1-42 and 1-40) and tau protein tangles/filaments. The disaggregation/dissolution of Aβ fibrils occurred nearly instantly when PTI-00703 cat's claw and Aβ fibrils were mixed together as shown by a variety of methods including Thioflavin T fluorometry, Congo red staining, Thioflavin S fluorescence and electron microscopy. Sophisticated structural elucidation studies identified the major fractions and specific constituents within PTI-00703 cat's claw responsible for both the observed "plaque" and "tangle" inhibitory and reducing activity. Specific proanthocyanidins (i.e. epicatechin dimers and variants thereof) are newly identified polyphenolic components within Uncaria tomentosa that possess both "plaque and tangle" reducing and inhibitory activity. One major identified specific polyphenol within PTI-00703 cat's claw was epicatechin-4β-8-epicatechin (i.e. an epicatechin dimer known as proanthocyanidin B2) that markedly reduced brain plaque load and improved short-term memory in younger and older APP "plaque-producing" (TASD-41) transgenic mice (bearing London and Swedish mutations). Proanthocyanidin B2 was also a potent inhibitor of brain inflammation as shown by reduction in astrocytosis and gliosis in TASD-41 transgenic mice. Blood-brain-barrier studies in Sprague-Dawley rats and CD-1 mice indicated that the major components of PTI-00703 cat's claw crossed the blood-brain-barrier and entered the brain parenchyma within 2 minutes of being in the blood. The discovery of a natural plant extract from the Amazon rain forest plant (i.e. Uncaria tomentosa or cat's claw) as both a potent "plaque and tangle" inhibitor and disaggregator is postulated to represent a potential breakthrough for the natural treatment of both normal brain aging and Alzheimer's disease.
大脑老化和阿尔茨海默病都表现为β-淀粉样蛋白含有“斑块”和tau 蛋白含有“缠结”的积累，这导致了加速的记忆丧失和认知能力下降。在本研究中，我们确定了一种特定的植物提取物及其成分，作为预防和减少大脑“斑块和缠结”的潜在天然解决方案。PTI-00703 猫爪（来自秘鲁特定来源的钩藤 Uncaria tomentosa）是一种来自亚马逊雨林的特定天然植物提取物，被鉴定为β-淀粉样纤维（“斑块”的主要成分）和 tau 蛋白配对螺旋丝/纤维（“缠结”的主要成分）的有效抑制剂和减少剂。PTI-00703 猫爪具有阻止形成/聚集和分散预先形成的 Aβ 纤维（1-42 和 1-40）和 tau 蛋白缠结/纤维的能力。当 PTI-00703 猫爪和 Aβ 纤维混合在一起时，Aβ 纤维的分散/溶解几乎立即发生，这通过包括 Thioflavin T 荧光法、刚果红染色、Thioflavin S 荧光和电子显微镜在内的各种方法得到证实。复杂的结构阐明研究确定了 PTI-00703 猫爪中负责观察到的“斑块”和“缠结”抑制和减少活性的主要部分和特定成分。特定的原花青素（即表儿茶素二聚体及其变体）是钩藤 Uncaria tomentosa 中新发现的多酚类成分，具有“斑块和缠结”减少和抑制活性。PTI-00703 猫爪中鉴定出的一种主要的特定多酚是表儿茶素-4β-8-表儿茶素（即一种称为原花青素 B2 的表儿茶素二聚体），它显著减少了年轻和老年 APP“斑块产生”（TASD-41）转基因小鼠（携带伦敦和瑞典突变）的脑斑块负荷并改善了短期记忆。原花青素 B2 还抑制了 TASD-41 转基因小鼠的脑炎症，如星形胶质细胞增生和神经胶质增生减少所示。在 Sprague-Dawley 大鼠和 CD-1 小鼠中的血脑屏障研究表明，PTI-00703 猫爪的主要成分在进入血液后 2 分钟内穿过血脑屏障并进入脑实质。从亚马逊雨林植物（即钩藤 Uncaria tomentosa 或猫爪）中发现的天然植物提取物既是一种有效的“斑块和缠结”抑制剂和分散剂，这被认为是天然治疗正常大脑老化和阿尔茨海默病的潜在突破。
