The Amazon rain forest plant Uncaria tomentosa (cat’s claw) and its specifc proanthocyanidin constituents are potent inhibitors and reducers of both brain plaques and tangles

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 fbrils (the main component of “plaques”) and tau protein paired helical flaments/fbrils (the main component of “tangles”). PTI-00703 cat’s claw demonstrated both the ability to prevent formation/aggregation and disaggregate preformed Aβ fbrils (1–42 and 1–40) and tau protein tangles/flaments. The disaggregation/dissolution of Aβ fbrils occurred nearly instantly when PTI-00703cat’s claw and Aβ fbrils were mixed together as shown by a variety of methods including ThiofavinT fuorometry, Congo red staining, Thiofavin S fuorescence and electron microscopy. Sophisticated structural elucidation studies identified the major fractions and specific constituents within PTI00703 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 identifed specifc polyphenol within PTI-00703 cat’s claw was epicatechin-4β-8-epicatechin (i.e. an epicatechin dimer known as proanthocyanidin B2) that markedly