In vitro comparison of major memory-support dietary supplements for their effectiveness in reduction/inhibition of beta-amyloid protein fibrils and tau protein tangles: key primary targets for memory loss

Abstract

Memory loss is primarily caused by the accumulation of both brain plaques [(consisting of beta-amyloid protein (Aβ) 1–42)] and neurofibrillary tangles (consisting of paired helical and straight filaments containing tau protein). Neuroinflammation is the third key and important factor that leads to accelerated memory loss and eventual dementia. Brain plaques, tangles and inflammation is the trilogy mainly responsible for causing memory loss that has now been documented for over 20 years in the scientific literature. The present investigation used in vitro quantitative methods to directly compare the ability of major memory-support dietary supplements to reduce pre-formed Aβ 1–42 fibrils (21 supplements tested) and tau protein paired helical/straight filaments (13 supplements tested)—two of the three most important targets for memory loss. Additionally, 18 different manufacturers of cat’s claw (Uncaria tomentosa) were directly compared for their ability to inhibit/reduce Aβ 1–42 fibrils and/or tau paired helical/straight filaments based on recent findings that PTI-00703 cat’s claw is a specific and potent inhibitor/reducer of all three targets -brain plaques, tangles and inflammation (Snow et al. in Sci Rep 9:561, 2019). In the present investigation quantitative Thioflavin T fluorometry was used on a comparative weight-to-weight basis at increasing concentrations with ingredients tested from the actual capsules the consumer ingests. Major memory-support dietary supplements were directly compared for their ability to inhibit and disaggregate/reduce both Aβ 1–42 fibrils and/or tau paired helical/straight filaments. Dietary supplements touted to enhance memory comparatively tested included Prevagen, FOCUSfactor, PROCERA AVH, Alpha Brain, NAD+OVIM, BRAIN JUICE, Cebria, EXCELEROL, NOOCUBE, US Doctor’s Clinical Brain Power ADVANCED, healthycell pro, LUMONOL, Brain Awake, BRAIN ARMOR, brainMD (BRAIN & MEMORY POWER BOOST), Brain Support, Clarity (BRAIN HEALTH FORMULA), brainMD (NEUROVITE PLUS), neuriva (Original and Plus) and percepta. This is the first paper to actually comparatively test these memory-support supplements for their ability to reduce Aβ fibrils and tau protein tangles. Percepta (PTI-00703 cat’s claw and a specific oolong tea extract) was determined to be the most effective and potent memory support dietary supplement to disaggregate/disrupt Aβ 1–42 fibrils (range of 25–89%) and tau paired helical/straight filaments (range of 26–86%) at all 3–4 doses tested in comparison to other major memory-support dietary supplements tested. This was at least more than double (> 50%) for percepta reducing Aβ 1–42 fibrils and in comparison to the other 20 memory-support dietary supplements tested. The ranking order for memory-support supplement effects based on reducing Aβ 1–42 fibrils (Aβ 1–42: memory-support supplement at 1:0.1 weight-to-weight in a 3-day study) was percepta (69.6% reduction) >>> Alpha Brain (34.9% reduction) = US Doctor’s Clinical Brain Power ADVANCED (32.4%) = BRAIN JUICE (30.1%) = neuriva Plus (27%) = neuriva Original (27%) > NEUROVITE PLUS (22.9%) = NOOCUBE (19.9%) = EXCELEROL (17.3%) = healthycell pro (17.2%) > Prevagen (12.9%) > PROCERA AVH (6.5%) = FOCUSfactor (5.5%) > Cebria (0%) = Brain Awake (0%) = Brain Support (0%) = brainMD (BRAIN & MEMORY POWER BOOST) (0%) = NAD+OVIM (0%) = BRAIN ARMOR (0%) = LUMONOL (0%). The ranking order for memory support supplement effects on reducing tau paired helical/straight filaments (tau:memory supplement at 1:1 weight-to-weight at 3 days) was percepta (85.7% reduction) >>> neuriva Plus (57.9%) >> BRAIN JUICE (41.9%) = EXCELEROL (41.0%) = neuriva Original (38.4%) = US Doctor’s Clinical Brain Power ADVANCED (38.3%) = healthycell pro (37.6%) >> Alpha Brain (27.9%) >> NOOCUBE (17.6%) >> FOCUSfactor (8.7%) > Cebria (3.6%) = PROCERA AVH (0%) = Prevagen (0%). Congo red staining, Thioflavin S fluorescence, circular dichroism (CD) spectroscopy and electron microscopy confirmed the positive results observed with the supplement percepta. CD spectroscopy demonstrated that percepta caused a marked inhibition of beta-sheet secondary folding of tau protein into paired helical filaments. PTI-00703 cat’s claw (main ingredient in percepta) was also identified as the most potent cat’s claw bark powder (Uncaria tomentosa) to reduce and inhibit Aβ 1–42 fibrils and tau tangles in comparison to 17 other manufacturers of cat’s claw extracts. Although there are thousands of brain memory-support dietary supplements in the marketplace today, none of them have been directly compared and analyzed for their ability to reduce and/or inhibit two major targets of memory loss i.e. Aβ 1–42 fibrils and tau paired helical/straight filaments (major constituents of brain plaques and tangles). In our comparison studies, we show that percepta has the most potent ability to disaggregate/reduce Aβ 1–42 fibrils and tau protein paired helical/straight filaments as demonstrated by a variety of methods most likely due to the specific polyphenol content in PTI-00703 cat’s claw (i.e. polyphenols and proanthocyanidins) as we have previously shown (Snow et al. in Sci Rep 9:561, 2019). Memory-support dietary supplements tested that also contained polyphenols and/or cat’s claw in their product demonstrated some Aβ fibril and tau protein tangle reducing activity, but were much less effective than percepta. Percepta’s main ingredient, PTI-00703 cat’s claw, has previously been shown to reduce brain amyloid plaques and Aβ 1–42/40 insoluble/soluble levels in brain (in plaque-producing transgenic mice) with marked concurrent memory improvements (shown by Morris water maze testing) (Snow et al. in Sci Rep 9:561, 2019). The present investigation further confirms that percepta is one of the best dietary supplements that causes a marked reduction and inhibition of Aβ fibrils and tau tangle filaments -two important major targets for memory-support. In addition, PTI-00703 cat’s claw was the most effective cat’s claw (Uncaria tomentosa) ingredient for reducing /disaggregating and inhibiting Aβ 1–42 fibrils and tau protein paired helical/straight filaments in comparison to 17 other manufacturers of cat’s claw extracts tested.

Potential Alzheimer's disease therapeutic nano-platform: Discovery of amyloid-beta plaque disaggregating agent and brain-targeted delivery system using porous silicon nanoparticles

“…The presence of Aβ plaques and amyloid-beta plaque disaggregation form (incubated with the screening candidates for 24 h) were also assessed by thioflavin S (ThS)-based fluorescence analysis [ 43 ]. The samples (Aβ plaques, Aβ plaques with screening candidates) were added to 1 mL of ThS (0.5%) solution.…”

“…The final nano-formulation was demonstrated to improve memory impairment through an animal behavioral experiment of the Aβ plaque-injected AD mouse model. In addition, changes in interleukin 6 (IL-6) level, which is known to be increased by Aβ plaques [ 41 , 42 ], and the amount of Aβ plaques in the hippocampus were also measured through Thioflavin S (ThS) staining [ 43 ].

Fig.

…”

Uncária Tomentosa (Wild.) D.C. em processos inflamatórios na doença de Alzheimer

“…para o tratamento da DA Em relação à DA, extratos hidroetanólicos demonstratram atividade in vitro contra agregação de proteína Aβ, formação de placas senis (Snow et al, 2019) e melhora da memória. 63 Em modelos animais, a utilização de extratos de U. Tomentosa vem demonstrando efeitos animadores. Em 2019, Snow e colaboradores demonstraram as ações in vitro e in vivo de um determinado extrato de unha de gato, PTI-00703, obtido a partir de fontes peruanas.…”

“…Além da potência evidenciada in vitro para inibição da formação de placas senis e agregação de proteína Aβ, modelos transgênicos tratados com o extrato PTI-777 apresentaram após 14 dias de tratamento com infusões no hipocampo e 30 dias de administração intraperitoneal uma redução significativa de formação destes marcadores para DA. 63 Xu e colaboradores 64 ao estudar ratos em que a DA foi mimetizada pela aplicação intracerebroventricular de estreptozocina, observaram que a administração de extratos hidroetanólicos por via intragástrica promoveram melhora de memória e aprendizado, sugerindo que os mecanismos envolvidos ocorreriam via inibição da proteína tau hiperfosforilada, a promoção da expressão de enzimas antioxidantes, a redução de citocinas pró-inflamatórias e pela ativação de Nrf2 mediada por Akt (Ser473)/GSK3β (Ser9).…”

Role of Herbal Teas in Regulating Cellular Homeostasis and Autophagy and Their Implications in Regulating Overall Health

“…Habitual tea consumption can reduce the risk of neurocognitive disorders [ 139 ]. The oolong tea extract in the form of dietary supplement “percepta” was able to reduce Aβ fibrils and tau protein tangles in vitro, as it caused a marked inhibition of beta-sheet secondary folding of tau protein into paired helical filaments [ 140 ]. Oolong tea extracts had a protective effect against glutamate-induced cell death in Neuro-2A and HT-22 cells.…”