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

Abstract

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.

Uncaria tomentosa(cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling

“…This study was performed to identify whether certain components of U. tomentosa extracts have potential therapeutic effects against COVID-19. To this purpose, a database of 26 compounds that have shown prevalence on the herbal therapeutic activity has been generated ( Figure 1) (Aquino et al, 1990(Aquino et al, , 1997Batiha et al, 2020;Keplinger et al, 1998;Kitajima et al, 2000;Lima-Junior et al, 2013;Lock et al, 2016;Montoro et al, 2004;Navarro et al, 2019Pavei et al, 2012;Peñaloza et al, 2015;Snow et al, 2019;Vera-Reyes et al, 2015). Our initial hypothesis is that cat's claw should contain molecules with highest therapeutic profiles against SARS-CoV-2, by disrupting SARS-CoV-2/ACE-2 association or by inhibiting SARS-CoV-2 spike protein.…”

“…Bioactive constituents of U. tomentosa extracts include proanthocyanidins [proanthocyanidin B2 (the main component), proanthocyanidin B4, proanthocyanidin C1, an epicatechin trimer, epiafzelechin-4b!8-epicatechin and an epicatechin tetramer] (Batiha et al, 2020;Navarro-Hoyos et al, 2017), oxindole alkaloids (isopteropodine, pteropodine, rhynchophylline, mytraphylline, speciophylline, uncarine F and uncarine E), indole alkaloidal glucosides (cadambine, 3dihydrocadambine and 3-isodihydrocadambine) (Batiha et al, 2020;Kura s et al, 2009;Laus et al, 1997;Lima-Junior et al, 2013;Lock et al, 2016;Navarro et al, 2019Snow et al, 2019), quinovic acid glycosides (Pavei et al, 2012), tannins (Ostrakhovich et al, 1997), polyphenols, catechins, beta sitosterol (Aquino et al, 1997;Navarro et al, 2019) and proteins (Lenzi et al, 2013), which individually or synergistically contribute to their therapeutic properties.…”

Evaluation of Natural and Botanical Medicines for Activity Against Growing and Non-growing Forms of B. burgdorferi

“…Uncaria tomentosa has documented neuroprotective effects in preclinical studies (110), and preliminary human studies have shown improved quality of life in individuals with cancer (111), enhanced DNA repair (112), and symptom improvement in individuals with rheumatoid arthritis (113) and osteoarthritis (114). The potential antimicrobial effects of Uncaria tomentosa have not been widely evaluated.…”

Evaluation of Natural and Botanical Medicines for Activity against Growing and Non-growing Forms ofB. burgdorferi

“…Uncaria tomentosa is an important medicinal plant from South and Central America and has been shown to have neuroprotective effects in preclinical studies (152) (and in preliminary human studies has been shown to improve quality of life in individuals with cancer (153), enhanced DNA repair (154), and symptom improvement in individuals with rheumatoid arthritis (155) and osteoarthritis (156). The potential antimicrobial effects of Uncaria tomentosa have not been widely evaluated.…”