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.

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Available from: Donald J Graves, Jan 12, 2015
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    • "Cinnamomum verum (Cinnamon) is a herb that has been traditionally used by many ancient cultures. It has been indicated for a variety of ailments, including gastrointestinal problems, urinary infections, symptoms of colds and flu, and possesses remarkable anti-fungal and anti-bacterial properties (Peterson et al., 2009). Some studies have shown that Cinnamon was also used traditionally in age related brain disorders (Peterson et al., 2009).The polyphenolic molecules that are present in the aqueous extract of Cinnamomum, may be responsible for the majority of properties of the plant. "
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    ABSTRACT: Introduction: Diagnosing and treating diseases associated with amyloid fibers remain a great challenge despite of intensive research carried out. One important approach in the development of therapeutics is the use of herbal extracts which are rich in aromatic small molecules. Cinnamomum verum extract (CE) contains proanthocyanidin and cinnamaldehyde, which have been suggested to be capable of directly inhibiting amyloid fibril formation in vitro. This study is aimed at characterizing the inhibitory activity of CE against the fibrillation of hen egg white lysozyme (HEWL). Methods: Acidic pH and high temperatures were used to drive the protein towards amyloid formation. Lysozyme was dissolved at 2 mg/mL in 50mM glycine buffer (pH 2.5), and then incubated at 57 °C for the specified durations while stirred gently by Teflon magnetic bars. Various techniques including thioflavin T, fluorescence, Congo red absorbance assay and AFM micrography were used to characterize the HEWL fibrillation processes. Results: In the absence of CE typical amyloid fibrils (like amyloids formed in Alzheimer disease) became evident after 48 h of incubation. Upon incubation with various extract concentrations in the range of 0.1-1 mg/ml, formation of fibrillar assemblies were significantly inhibited (p<0.05). AFM analysis and MTT assay also confirmed the role of the extract in amyloid inhibition. Our studies showed that the presence of CE did not have any effect on protein stabilization and thus directly interact with amyloid structure and inhibit formation of these structures. Furthermore, a docking experiment showed that a pi-pi interaction may occur between the aromatic component of cinnamaldehyde and W62. Interestingly, W62 is one of the principal aromatic residues that interact with glycine amide, which is an aggregation suppressor of HEWL. Discussion: These observations suggest that aromatic small molecules of CE may directly insert into amyloidogenic core of early aggregates and inhibit amyloid fibril formation by disrupting the pi-pi interactions.
    Full-text · Article · Jan 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.
    Full-text · Article · Mar 2014 · PLoS ONE
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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.
    Full-text · Article · Oct 2013 · BMC Complementary and Alternative Medicine
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