Scientific Breakthrough on Preventing the Formation of Amyloid Plaque

Large amounts of amyloid plaque have been found in the brains of all Alzheimer’s patients when an autopsy has been performed. This plaque is called beta-amyloid protein and referred to by scientists as “Abeta.” In the current search for anti-Alzheimer’s Disease drugs, researchers have been intensively studying what they call “amyloidism,” with a focus on finding ways to modify the process of accumulation of Abeta in the brain. The scientists have uncovered four paths to prevent or stop Abeta accumulation in the brain: (i) reduction of Abeta production; promotion of the Abeta degrading catabolic pathway; (iii) immunotherapy for Abeta and (iv) inhibition of Abeta aggregation.

In investigating the fourth avenue of research – how to inhibit the accumulation or aggregation of Abeta, attention has been focused both on chemical compounds developed in the laboratory and on compounds found in botanicals which can chemically bind the plaque so that it can be excreted or eliminated out of the body through the bowel. Several studies have been performed on the binding capacity of compounds found in Cat’s Claw (Uncaria tomentosa) to Abeta with promising results.

Cell Mol Life Sci. 2006 Jul;63(13):1538-52.

Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease.

Hamaguchi T, Ono K, Yamada M.
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1, Takara-machi, Kanazawa, 920-8640, Japan.

Deposition of amyloid beta-protein (Abeta) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Abeta in the brain. Here, we review four anti-amyloidogenic strategies: (i) reduction of Abeta production, which has mainly been approached with secretase inhibition, (ii) promotion of the Abeta degrading catabolic pathway, including an Abeta degrading enzyme, neprilysin, (iii) immunotherapy for Abeta and (iv) inhibition of Abeta aggregation. We have reported that AD patients have a favorable molecular environment for Abeta aggregation and that various compounds, such as polyphenols, interfere with Abeta aggregation and destabilize preformed Abeta fibrils.

Z Naturforsch C. 2006 Nov-Dec;61(11-12):821-6.

Binding of an oxindole alkaloid from Uncaria tomentosa to amyloid protein (Abeta1-40).

Frackowiak T, Baczek T, Roman K, Zbikowska B, Glensk M, Fecka I, Cisowski W.
Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gen. J. Hallera 107, 80-416 Gdansk, Poland. teresafr@amg.gda.pl

The primary aim of this work was to determine the interactions of an oxindole alkaloid (mitraphylline) isolated from Uncaria tomentosa with beta-amyloid 1-40 (Abeta1-40 protein) applying the capillary electrophoresis (CE) method. Specifically the Hummel-Dreyer method and Scatchard analysis were performed to study the binding of oxindole alkaloids with Abeta1-40 protein. Prior to these studies extraction of the alkaloid of interest was carried out. Identification of the isolated alkaloid was performed by the use of thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) combined with electrospray ionization mass spectrometry (ESI-MS). The proposed approach was proved to be an efficient and accurate method for specific compound isolation and identification purposes. Moreover, analytical information from the CE approach can be considered as the valuable tool for binding constant determination. The binding constant of mitraphylline with Abeta1-40 protein determined by the Hummel-Dreyer method and Scatchard analysis equals K = 9.95 x 10(5) M(-1). The results obtained showed the significant binding of the tested compound with Abeta1-40 protein. These results are discussed and interpreted in the view of developing a strategy for identification of novel compounds of great importance in Alzheimer disease therapy.

Fujiwara H, et. al
Department of Geriatric and Complementary Medicine, Center for Asian Traditional Medicine Research, Tohoku University School of Medicine, Sendai, Japan.

Because the deposition of beta-amyloid protein (Abeta) is a consistent pathological hallmark of Alzheimer’s disease (AD) brains, inhibition of Abeta generation, prevention of Abeta fibril formation, or destabilization of preformed Abeta fibrils would be attractive therapeutic strategies for the treatment of AD. We examined the effects of several medicinal herbs used in traditional Chinese medical formulae on the formation and destabilization of Abeta fibrils by using the thioflavin T binding assay, atomic force microscopic imaging, and electrophoresis. Our study demonstrates that several of these herbs have potent inhibitory effects on fibril formation of both Abeta(1-40) and Abeta(1-42) in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited Abeta aggregation most intensively. Significant destabilization of preformed Abeta(1-40) and Abeta(1-42) fibrils was also induced by Uncaria rhynchophylla as well as some other herb extracts. Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective. Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.