Cinnamon Reduces Neurodegeneration
Aside from its ability to help with diabetes …
Cinnamon and its metabolite sodium benzoate arecapable of upregulating neurotrophic factors such as BDNF
Neurotrophic factors are a family of small proteins that are secreted to enhance the ability of signalling neurons to survive, differentiate, and even grow. As well, neurotrophic factors may act as rescuers of susceptible neurons in many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and HIV-associated dementia. In memory diseases, the levels of certain neurotrophic factors are pointedly reduced in the brain. As an example, it has been shown that the levels of brain-derived neurotrophic factors(BDNF) and neurotrophin-3 (NT-3) are significantly downregulated in patients with Alzheimer’s disease (AD).
Cinnamon May Help Alzheimer’s
An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of beta-amyloid polypeptide (Aβ) play a key role in Alzheimer’s disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in an AD model mouse. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization had remained an unmet challenge.
In a recent study, researchers identified a natural substance, based on cinnamon extract which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells.1 This is consistent with extensive research over the last 10 years indicating that extracts derived from such spices as turmeric and cinnamon target inflammatory pathways, which may prevent neurodegenerative diseases.
These results present a novel
prophylactic approach for inhibition
of toxic oligomeric Aβ species
formation in AD through the
utilization of a compound that is
currently in use in the human diet.
When administered to an AD fly model, cinnamon altered their reduced longevity, fully recovered their locomotion defects and totally abolished certain species of Aβ in their brain. Furthermore, oral administration of cinnamon to an aggressive AD transgenic mouse model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques, and improvement in cognitive behavior. These results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in the human diet, and which has been found to be of value for type 2 diabetes.
Reference
- Frydman-Marom A, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, Vassar R, Segal D, Gazit E, Frenkel D, Ovadia M. Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer’s disease animal models. PLoS One 2011 Jan 28;6(1):e16564.
Neurotrophic Factors Blocked by Blood-Brain Barrier
Consequently, these neurotrophic factors exhibit protective effects in cell culture and animal models of different neurodegenerative disorders.1 Thus, the idea of increasing their levels and/or maintaining their physiological levels in the central nervous systems of those with neurodegenerative disorders is an important area of research. Unfortunately, clinical application of those molecules has been limited because of difficulties in delivery. These small proteins do not readily diffuse across the blood–brain barrier or ventricular lining and have limited or unstable bioavailability.1
Neurotrophic factors may act as
rescuers of susceptible neurons in
many neurodegenerative diseases
including Alzheimer’s disease,
Parkinson’s disease, and HIV-
associated dementia.
Cinnamon Can Upregulate Neurotrophic Factors
Recently, it has been shown that orally administered cinnamon extract protects memory in a mouse model of AD (see “Cinnamon Corrects Cognitive Impairment in Alzheimer’s” in the October 2011 issue of Life Enhancement). Several lines of evidence presented in the study references in that article clearly support the conclusion that cinnamon and its metabolite sodium benzoate (NaB) are capable of upregulating neurotrophic factors.
Cinnamon is commonly used for flavoring, along with its naturally produced metabolite NaB, which is widely used as a food preservative. As well, NaB is an FDA-approved drug for the treatment of urea cycle disorders in children. Earlier, the researchers of a new paper1 had demonstrated that NaB modifies T cells at multiple steps and protects experimental allergic encephalomyelitis, an animal model of multiple sclerosis.
In their new paper,1 the authors—from the Department of Neurological Sciences, Rush University Medical Center and the University of Illinois in Chicago—concluded from their observations that NaB dose-dependently induces the expression of BDNF and NT-3 in primary human astrocytes and neurons. This upregulation was specific to NaB as sodium formate (NaFO), a compound structurally similar to NaB but without having the benzene moiety, had no effect on the mice used in their experiment.
Reducing or Delaying Neurodegeneration
In the course of the study, after oral feeding, NaB entered into the brains of the mice in vivo and upregulated BDNF and NT-3. Following this, oral administration of ground cinnamon increased the level of NaB in blood and the brains of the mice and upregulated BDNF and NT-3 in vivo in their brains. Because the loss of these neurotrophic factors has been implicated in the pathogenesis of various neurodegenerative diseases, these results provide a potentially important mechanism whereby cinnamon and its metabolite NaB may reduce or delay neurodegeneration.
The idea of increasing neurotrophic-
factor levels and/or maintaining their
physiological levels in the central
nervous systems of those with
neurodegenerative disorders is an
important area of research.
Clarification of Neurotrophic Signaling Events Required for Transcription.
“The signaling events required for the transcription of neurotrophic factors are becoming clear,” write the authors of the current paper.1 What their analysis shows is that the chief promotor that controls transcription of BDNF is cAMP* response element binding (CREB), which plays an important role in the expression of various neurotrophic factors. Of these factors, the activation of CREB seems essential, and NaB induces the activation of protein kinase A (PKA), which in turn recruits CREB. Together, CREB and PKA are crucial to the molecular energy of memory. [See Fig. 1]*Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3’-5’-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is derived from adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.
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Diabetes May Double Alzheimer’s Disease Probability
A growing body of literature suggests that diabetes-related cognitive dysfunction is largely a consequence of changes within the central nervous system that are secondary to chronic hyperglycemia. The cerebrovascular changes, oxidative stress, increased advanced glycation end products, and impairments in cerebral insulin signaling systems are thought to be the underlying causes for diabetic dementias. Furthermore, diabetes seems to double the probability of developing Alzheimer’s disease and other dementias.1,2 Cinnamon may be useful to help As stated above, anti-oxidants, antihyperglycemics, and insulin-sensitizing agents are reported to reduce cognitive dysfunction in diabetes. And recent evidence suggests that glucagon-like peptide-1 (GLP-1) plays an important role in diabetes and cognitive dysfunction. It has also been demonstrated that GLP-1 is involved in learning, and neuroprotection. However, at the time of the above-cited research, there were no specific treatments available for the management and/or prevention of cognitive dysfunction in type 2 diabetes. However, more recent research has shown that the ingestion of 3 g cinnamon by healthy subjects reduces postprandial (after eating) serum insulin and increases GLP-1 concentrations.3 These results indicate a relation between the amount of cinnamon consumed and the decrease in insulin concentration and GLP-1 and suggest that cinnamon may be useful to help prevent the development of Alzheimer’s disease. References
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So the metabolite of cinnamon, NaB exerts its neurotrophic effect through the activation of CREB through the increased activity of PKA and the level of phospho-CREB in vivoin the central nervous systyem. These results highlight a novel neurotrophic property of cinnamon and its metabolite NaB via the PKA – CREB pathway, which may be of benefit for various neurodegenerative disorders.
These results provide a potentially
important mechanism whereby
cinnamon and its metabolite NaB
may reduce or delay
neurodegeneration.
Two for the Price of One
These results highlight undiscovered properties of cinnamon and NaB and indicate that these compounds may be used for therapeutic intervention in neurodegenerative disorders as primary or adjunctive therapy. And since the toxicity is very low for cinnamon, which ensures production of NaB, the supplementary use of cinnamon is a nutritional “twofer.” What’s good for blood sugar metabolism is also good for your mind.
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Berberine Enhances Memory
Berberine, an isoquinoline alkaloid, similar to cinnamon in its antidiabetic and antioxidant effects, also offers nootropic benefits. In a recent study conducted to evaluate the effect of berberine on hippocampal neuronal cell death, synaptic plasticity and learning and memory induced in streptozotocin (STZ)-diabetic rats, the results were encouraging.1 Long-term potentiation was recorded for synaptic plasticity and potential amplitude, and these features were found to decrease in a diabetic group versus control. However, chronic oral berberine treatment (100 mg/kg/day) provided long term potentiation while simultaneously improving learning, reducing memory impairment, and decreasing cell suicide of pyramidal neurons in the hippocampus (the seat of emotions in the brain). In summary, chronic berberine treatment of STZ-diabetic rats significantly ameliorates learning and memory impairment and part of its beneficial effect could be attributed to improvement of synaptic dysfunction and anti-apoptotic (cell suicide) properties. In another study, daily administration of berberine and one of its sources (Phellodendron amurense) improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test by enabling rats to find the submerged platform more readily.2 In yet another study, the therapeutic effect of berberine extracted from the Chinese medical herb Coptis chinensis Franch, found that berberine treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. Also, there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in the brains of berberine-treated mice. And a major kinase involved in amyloid precursor protein and tau phosphorylation was significantly inhibited by berberine treatment. Altogether, the results suggest that berberine provides neuroprotective effects in mice through regulating amyloid precursor protein processing. Twofer Twofer In a formulation that contains both cinnamon and berberine, we have a two-times-two factor. Each ingredient delivers antidiabetic and pro-memory benefits. How can you beat that? References
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Reference
- Jana A, Modi KK, Roy A, Anderson JA, van Breemen RB, Pahan K. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders. J Neuroimmune Pharmacol. 2013 Mar 9. [Epub ahead of print] PubMed PMID: 23475543.