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


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.

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Available from: Donald J Graves, Jan 12, 2015
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    • "Notably, cinnamon was not able to exert significant effects in type 1 diabetic patients while its insulin-like effects were present in type 2 diabetic patients [4]. Interestingly, cinnamon extract was described as beneficial in Alzheimer's disease by reducing β-amyloid oligomerization and cognitive decline [10]–[11], and cinnamon further prevented glutamate-induced neuronal death in cultured cerebellar granule cells [12]. "
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    ABSTRACT: Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.
    PLoS ONE 03/2014; 9(3):e92358. DOI:10.1371/journal.pone.0092358 · 3.23 Impact Factor
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    • "An aqueous extract of CZ is known to inhibit tau aggregation and filament formation, which are hallmarks of Alzheimer’s disease [68]. The extract also promotes complete disassembly of recombinant tau filaments and cause substantial alteration of the morphology of paired-helical filaments isolated from brains of those with Alzheimer’s disease, however it was not deleterious to the normal cellular function of tau. "
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    ABSTRACT: In traditional medicine Cinnamon is considered a remedy for respiratory, digestive and gynaecological ailments. In-vitro and in-vivo studies from different parts of the world have demonstrated numerous beneficial medicinal effects of Cinnamomum zeylanicum (CZ). This paper aims to systematically review the scientific literature and provide a comprehensive summary on the potential medicinal benefits of CZ. A comprehensive systematic review was conducted in the following databases; PubMed, Web of Science, SciVerse Scopus for studies published before 31st December 2012. The following keywords were used: "Cinnamomum zeylanicum", "Ceylon cinnamon", "True cinnamon" and "Sri Lankan cinnamon". To obtain additional data a manual search was performed using the reference lists of included articles. The literature search identified the following number of articles in the respective databases; PubMed=54, Web of Science=76 and SciVerse Scopus=591. Thirteen additional articles were identified by searching reference lists. After removing duplicates the total number of articles included in the present review is 70. The beneficial health effects of CZ identified were; a) anti-microbial and anti-parasitic activity, b) lowering of blood glucose, blood pressure and serum cholesterol, c) anti-oxidant and free-radical scavenging properties, d) inhibition of tau aggregation and filament formation (hallmarks of Alzheimer's disease), e) inhibitory effects on osteoclastogenesis, f) anti-secretagogue and anti-gastric ulcer effects, g) anti-nociceptive and anti-inflammatory activity, h) wound healing properties and i) hepato-protective effects. The studies reported minimal toxic and adverse effects. The available in-vitro and in-vivo evidence suggests that CZ has many beneficial health effects. However, since data on humans are sparse, randomized controlled trials in humans will be necessary to determine whether these effects have public health implications.
    BMC Complementary and Alternative Medicine 10/2013; 13(1):275. DOI:10.1186/1472-6882-13-275 · 2.02 Impact Factor
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    • "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
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