Article

Cinnamon Extract Inhibits Tau Aggregation Associated with Alzheimer's Disease In Vitro

Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 06/2009; 17(3):585-97. DOI: 10.3233/JAD-2009-1083
Source: PubMed

ABSTRACT An aqueous extract of Ceylon cinnamon (C. zeylanicum) is found to inhibit tau aggregation and filament formation, hallmarks of Alzheimer's disease (AD). The extract can also promote complete disassembly of recombinant tau filaments and cause substantial alteration of the morphology of paired-helical filaments isolated from AD brain. Cinnamon extract (CE) was not deleterious to the normal cellular function of tau, namely the assembly of free tubulin into microtubules. An A-linked proanthocyanidin trimer molecule was purified from the extract and shown to contain a significant proportion of the inhibitory activity. Treatment with polyvinylpyrolidone effectively depleted all proanthocyanidins from the extract solution and removed the majority, but not all, of the inhibitory activity. The remainder inhibitory activity could be attributed to cinnamaldehyde. This work shows that compounds endogenous to cinnamon may be beneficial to AD themselves or may guide the discovery of other potential therapeutics if their mechanisms of action can be discerned.

Download full-text

Full-text

Available from: Donald J Graves, Jan 12, 2015
2 Followers
 · 
254 Views
  • Source
    • "For instance, the interaction of prion protein with fulvic acid and its inhibitory effect on the content of β-sheet structure and the formation of protein aggregates has been described in detail. Only a few polyphenolic molecules have emerged to prevent tau aggregation, and natural drugs targeting against tau have not been approved yet (Peterson et al., 2009; Cornejo et al., 2011). Fulvic acid, a humic substance, has several nutraceutical properties with potential activity to protect cognitive impairment. "
    When Things Go Wrong - Diseases and Disorders of the Human Brain, 02/2012; , ISBN: 978-953-51-0111-6
  • Source
    • "Despite this, there are few phytocomplexes emerging to prevent tau aggregation . Only a cinnamon extract and a grape seed polyphenolic extract have been described for this purpose [20] [21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease is a neurodegenerative disorder involving extracellular plaques (amyloid-β) and intracellular tangles of tau protein. Recently, tangle formation has been identified as a major event involved in the neurodegenerative process, due to the conversion of either soluble peptides or oligomers into insoluble filaments. At present, the current therapeutic strategies are aimed at natural phytocomplexes and polyphenolics compounds able to either inhibit the formation of tau filaments or disaggregate them. However, only a few polyphenolic molecules have emerged to prevent tau aggregation, and natural drugs targeting tau have not been approved yet. Fulvic acid, a humic substance, has several nutraceutical properties with potential activity to protect cognitive impairment. In this work we provide evidence to show that the aggregation process of tau protein, forming paired helical filaments (PHFs) in vitro, is inhibited by fulvic acid affecting the length of fibrils and their morphology. In addition, we investigated whether fulvic acid is capable of disassembling preformed PHFs. We show that the fulvic acid is an active compound against preformed fibrils affecting the whole structure by diminishing length of PHFs and probably acting at the hydrophobic level, as we observed by atomic force techniques. Thus, fulvic acid is likely to provide new insights in the development of potential treatments for Alzheimer's disease using natural products.
    Journal of Alzheimer's disease: JAD 07/2011; 27(1):143-53. DOI:10.3233/JAD-2011-110623 · 4.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As a critical factor in the induction of angiogenesis, vascular endothelial growth factor (VEGF) has become an attractive target for anti-angiogenesis treatment. However, the side effects associated with most anti-VEGF agents limit their chronic use. Identification of naturally occurring VEGF inhibitors derived from diet is a potential alternative approach, with the advantage of known safety. To isolate natural inhibitors of VEGF, we established an in vitro tyrosine kinase assay to screen for diet-based agents that suppress VEGFR2 kinase activity. We found that a water-based extract from cinnamon (cinnamon extract, CE), one of the oldest and most popular spices, was a potent inhibitor of VEGFR2 kinase activity, directly inhibiting kinase activity of purified VEGFR2 as well as mitogen-activated protein kinase- and Stat3-mediated signaling pathway in endothelial cells. As a result, CE inhibited VEGF-induced endothelial cell proliferation, migration and tube formation in vitro, sprout formation from aortic ring ex vivo and tumor-induced blood vessel formation in vivo. Depletion of polyphenol from CE with polyvinylpyrrolidone abolished its anti-angiogenesis activity. While cinnamaldehyde, a component responsible for CE aroma, had little effect on VEGFR2 kinase activity, high-performance liquid chromatography-purified components of CE, procyanidin type A trimer (molecular weight, 864) and a tetramer (molecular weight, 1152) were found to inhibit kinase activity of purified VEGFR2 and VEGFR2 signaling, implicating procyanidin oligomers as active components in CE that inhibit angiogenesis. Our data revealed a novel activity in cinnamon and identified a natural VEGF inhibitor that could potentially be useful in cancer prevention and/or treatment.
    Carcinogenesis 12/2009; 31(3):481-8. DOI:10.1093/carcin/bgp292 · 5.27 Impact Factor
Show more