Cinnamon is the inner bark of trees named Cinnamomum. Studies have shown that cinnamon and its bioactive compounds can influence brain function and affect behavioral characteristics. This study aimed to systematically review studies about the relationship between cinnamon and its key components in memory and learning.
In vivo studies showed that using cinnamon or its components, such as eugenol, cinnamaldehyde, and cinnamic acid, could positively alter cognitive function. In vitro studies also showed that adding cinnamon or cinnamaldehyde to a cell medium can reduce tau aggregation, Amyloid β and increase cell viability.
innamon after TBI: Studies investigating the therapeutic efficacy of cinnamon in inflammatory neurodegenerative disorders have revealed that compounds endogenous to cinnamon exerted significant anti-Alzheimer effect through improved insulin signalling and cognitive dysfunction (Kawatra et al., 2015).
In line with this, experimental models of Alzheimer’s disease and diabetes mellitus have suggested that cinnamon showed significant pro-cognitive effects that contained decreased oxidative stress and declined streptozotocin-induced impairment in acetyl cholinesterase activity (Bramlett and Dietrich, 2002; Chen et al., 2004; Shively et al., 2012; Jain et al., 2014).
The anti-amyloid activity of cinnamon was confirmed with further studies showing that cinnamon significantly suppressed the β-secretase enzyme activity (Bramlett and Dietrich, 2002; Chen et al., 2004; Shively et al., 2012; Jain et al., 2014). Recent data also revealed that cinnamon regulated glucose levels and exerted insulinomimetic effects via signaling proteins, peroxisome proliferator activated receptor and the expression of insulin-sensitive glucose transporters (Sheng et al., 2008).
Considering the fact that even mild-increased glucose levels are an important risk for Alzheimer’s disease (Kawatra et al., 2015), it is logical to think cinnamon might have a multifaceted therapeutic role in Alzheimer’s disease.
In our very recent study, we have evaluated cinnamon’s neuroprotective activity after TBI in mice (Yulug et al., 2018). Thirty minutes after performing the cryogenic brain trauma model, we have applied 10 mg/kg intraperitoneally cinnamon and analyzed the infarct and edema volumes along with the expression of inflammatory and anti-oxidant protein levels.
Not surprisingly, we have shown for the first time that cinnamon reduced the infarct volume, edema formation and supressed inflammation and oxidative injury after TBI which suggested that cinnamon could be a promising therapeutic agent for neurodegenerative disorders characterized by increased inflammation and oxidative stress. Another important message of our study was that promising neuroprotective agents should be applied within the latent time period where increased oxidative injury and inflammation are deemed to play a vital role in the pathogenesis of TBI.
Considering that multi-drug interactions may also limit the neuroprotective activity of each single candidate agent, it is not unreasonable to assume that a multi-potent single agent acting on multiple pathophysiological cascades might provide a greater neuroprotective effect. However, many clinical trials have failed to show an effective neuropharmacological treatment for the primary and secondary outcomes after TBI in humans (i.e., clinical and cognitive outcomes).
In our previous experimental TBI study (Yulug et al., 2018), we were not surprised to reveal that cinnamon treatment regulated various anti-oxidant enzymes and inflammatory cytokines. However, the most interesting finding was that cinnamon significantly increased nuclear erythroid factor-2 which is a potent inductor of the endogenous anti-oxidant pathways and regulates the inflammatory and anti-oxidative pathways through nuclear factor kappa B during the TBI (Kelestimur et al., 2016; Yulug et al., 2018).
It should be noted that we also have revealed increased neural cell adhesion molecule levels after cinnamon treatment that is an important mediator of neurogenesis and axonal growth (Murray et al., 2016; Yulug et al., 2018). From a clinical perspective, a recent human study has revealed that polysialated neural cell adhesion molecule levels were significantly reduced in the entorhinal cortex that were inversely correlated with hyperphosphorylated tau load (Murray et al., 2016).
In paralell with that, amyloid-β-dependent disruption of hippocampal neural cell adhesion molecule 2 augmented significantly the synapse loss in Alzheimer’s disease (Leshchyns’ka et al., 2015). In line with this, a recent human study has revealed that reduced polysialated neural cell adhesion molecule levels were inversely correlated with hyperphosphorylated tau load in the entorhinal cortex (Murray et al., 2016).
Properties of Compounds Naturally Occurring in Cinnamon
Antioxidant compounds are important in human life as health-protective agents. They are present in natural food, but they are also additives in the food industry used to prevent deterioration. One of the sources of antioxidant compounds is cinnamon. This simple spice can affect diseases. Ervina et al.  showed that cinnamon bark infusion has high antioxidant activities due to the presence of polyphenols and volatile oil compounds. Simple preparation of extract can be applied as a high antioxidant issue [36,37].
Cinnamon spice is a source of natural antioxidants that play a key role in the process of aging and diseases. Cinnamomum zeylanicum and Cinnamomum cassia (L.) J. Presl have the highest potential. Extract from the bark of this kind contains biologically active compounds such as eugenol, trans-cinnamaldehyde, and linalool. Phytonutrients have been investigated in the stabilization of palm oil. They prevent the generation of alcohols, ketone, aldehyde, acids, and hydrocarbons. The addition of antioxidants inhibits episodes of the oxidation process of oil, reducing the production of dangerous oxidative derivates and free fatty acids .
As mentioned, compounds contained in cinnamon can also be applied as health-protective agents. Encapsulating cinnamon antioxidants increases their antioxidant efficacy. A diet enriched with these compounds brings benefits, contributing to a decrease in inflammation-triggering oxidative stress . Antioxidants are regarded as factors of progress and are associated with human life due to their influence on metabolic diseases (e.g., glycemic diseases). However, the yield of potential extracts from cinnamon depends on the maturity of plants. Prabhashini et al.  confirmed that mature cinnamon leaves are most effective in managing oxidative stress related to chronic disease.
The main compound supporting natural medicine is cinnamaldehyde and its analogues. However, two new compounds were investigated: lignan pinoresinol (PRO) and flavonol (-)-(2R,3R)-5,7-dimethoxy-3’,4’-methylenedioxy-flavan-3-ol (MFO), which are also important in natural medicine as inhibitors of effects of oxidative stress . According to the phenolic profile, the main compounds of water extracts of cinnamon are p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, vanillin, and gallic acid, but ethanol extracts additionally contain ascorbic acid.
They are multifunctional biologically active compounds, reducing Fe3+ and Cu2+ and inhibiting some enzymes. Ethanol extracts were more effective against α-glucosidase, butyrylcholinesterase (BChE), and α-amylase as an inhibitor .
Cinnamon can be also used as preservatives in food products. (E)-Cinnamaldehyde is applied as a factor inhibiting the activation of tyrosinase as a suppressor of hyperpigmentation, the browning effect observed in fruits, vegetables, and mushrooms.
Hence, cinnamon agents are related to a wide range of applications, such as in disease, the food industry, medicine, and the cosmetic industry .
Tannins, phenolic derivatives, are one of the groups of nonvolatile bioactive compounds determined in cinnamon. They have antioxidant properties and promising therapeutic potential for treating various diseases and metabolic disorders. Both classes of these compounds are present in cinnamon: condensed tannins (proanthocyanidins) and hydrolysable tannins . Tannins exhibit beneficial pharmacological effects. Hydrolysis of tannins in a microbial setting results in the formation of bioavailable metabolites responsible for the beneficial systemic effects .
Tannin quantity is determined at the percentage level and depends on the species of cinnamon . The tannin contents (expressed as catechin equivalent) of Cinnamomum zeylanicum and Cinnamomum cassia (L.) J. Presl were 2.18% and 0.65%, respectively. In another study , LC–MS analysis showed that extract from Cinnamomum burmannii contained high levels of condensed tannins, proanthocyanidins (23.2%), and (epi)catechins (3.6%).
Diabetes is a metabolic disorder that can cause many health complications. Diabetes mellitus type 2 is the most common. Traditional medicine is based on synthetic drugs, but herbal ones are becoming increasingly popular due to their bioactive properties. The main strategy is associated with the inhibition of α-amylase and α-glucosidase enzymes, which are related to the hydrolysis of carbohydrates in the digestive tract.
In the water extract of Cinnamomum zeylanicum prepared using high pressure and the decoction method, benzoic acid, (E)-cinnamaldehyde, trans-cinnamic acid, eugenol, and o-methoxy-cinnamaldehyde were found. These bioactive compounds extracted by this method have huge potential to inhibit α-glucosidase and control hyperglycemia .
Cinnamaldehyde is a predominant compound in the bark oil extracted from Cinnamomum zeylanicum. It seems to reduce plasma glucose levels more effectively than metformin, which is commonly used in traditional medicine. Bioactive compounds of cinnamon oil enhance the expression of proteins that play a key role during glucose transport, insulin signaling, and the regulation of dyslipidemia.
Disturbances in the balance between free radicals and oxidative stress can also lead to tissue damage. Oxidative stress at a high level increases insulin resistance. This causes impairment of glucose tolerance and diabetes type 2. This research confirmed that cinnamon consists of bioactive compounds that ensure this balance [47,48].
Cinnamon in the Treatment of Diseases and Disorders
Cinnamon is well known in Western natural medicine as a natural species with healing properties. Nowadays, it is also reported as a plant with special attributes used to treat many disorders (Figure 2).
Traumatic brain injury is a devastating disease that ranges from reversible neurochemical cascades to neuronal damage and behavioral impairment. Inflammation, injury, blood–brain barrier disruption, excitotoxicity, ionic homeostasis, and mitochondrial dysfunction play a critical role in the development of different neurological disorders. The majority of conservative medicinal therapies fail to limit the injury after traumatic brain injury (TBI) .
Most clinical research shows that early intervention and treatment are the only way to slow down or reverse the disease. Components of diet affect the incidence, severity, and management of many health issues, such as chronic diseases . Alzheimer’s disease (AD) is caused by the degeneration of neuron-rich regions. Acetylcholine is correlated with memory function. Treatment of AD consists of the application of inhibitors of cholinesterase. However, they cannot modify the course of the disease. There are also other causes of AD, such as the presence of senile plaques, which contain fibrils composed of amyloid beta peptide and hyperphosphorylated tau protein .
Oxidative stress can produce oligomers Aβ through the activation of enzymes to reduce the production of amyloid β, which make the formation of amyloid plaque highly possible . Polyphenolic derivatives present in the cinnamon extract are active against the alteration of oxidative stress enzymes.
Cinnamomum zeylanicum was able to provide protection against Alzheimer’s disease and dementia in scopolamine-induced memory impairment experimental rat models attributed to a certain reduction in the measurement of malondialdehyde (MDA) and glutathione oxidative stress parameters . The activity of cinnamon aldehyde depends on the amount of its metabolites. This bioactive compound is well distributed through the body. Part of aldehyde is metabolized into hippuric acid in the liver and methyl cinnamate and cinnamyl alcohol in the plasma. The interaction of polyphenols with the blood barrier is a determining factor .
Parkinson’s disease (PD) is one of the most common neurological disorders. PD patients display both motor and nonmotor symptoms. PD disease is related to neurodegeneration in the midbrain structure called black matter, and it leads to a decrease in the levels of dopamine in the brain. One of the conceptions regarding aging and the loss of essential black cells is connected to the decrease in dopamine in the organism. Additionally, oxidative stress and free radicals play a role.
However, many factors indicate PD. In the pathomorphological image of PD, inside the neurons Lewy bodies are visible. They are built from α-synuclein protein. PD patients are characterized by an abnormal conformation of this protein, which leads to the secondary accumulation of β-amyloid and consequently to death .
Research on the medicinal properties of cinnamon oil in PD suggests that the extract may have an effect on neurons and can delay the progression of several neurological disorders. Cinnamon can modulate several intracellular pathways and functions of mitochondria. Mutation of the DJ-1 gene is responsible for some autosomal recession and early-onset PD. It is connected to oxidative stress and mitochondrial dysfunction .
According to several studies, sodium benzoate (a component of cinnamon extract) can reverse the lipopolysaccharide-induced inhibition of the DJ-1 gene in neurons and exert neuroprotective effects. Compounds of cinnamon extract are responsible for the regulation of mitochondria and apoptosis functioning. Cinnamon compounds containing sodium benzoate are promising natural products against PD .
Other Applications of Cinnamon
To date, a number of studies have been carried out to check the bioactivity of cinnamon compounds against diseases. Cinnamon is rich in cinnamic acid, cinnamic aldehyde, cinnamyl acetate, α-thujene, terpineol, α-cubebene, eugenol, and coumarin. These compounds have strong antibacterial and anti-inflammatory properties and influence biological processes in the human body .
Scientific literature studies suggest that species of Cinnamomum are used in traditional medicine to treat a multitude of daily disorders, such as colds, indigestion, coughs, and microbial infections. Extracts from cinnamon released during ingestion have a positive effect on the treatment of diseases.
Cinnamon is used as a medicine for stomachache, chest tightness, diarrhea, dyspepsia, and gastritis . Cinnamon bark oil is used to treat indigestion, diabetes, acne, respiratory, and urinary disease. Cinnamon shows a therapeutic activity in benign prostatic hyperplasia. This is achieved by inhibiting the protein specific to the prostate .
The water extract of cinnamon leaves is used to treat alopecia. It significantly promotes the proliferation of human hair dermal papilla cells .
The bioactive properties of cinnamon compounds can affect the growth of Escherichia coli, which can cause common urinary infections . The application of patches with cinnamon extract brings positive results in the treatment of overactive bladder syndrome and urinary incontinence .
Cinnamon is also one of the nutraceuticals. It is a natural food ingredient with pharmacological properties. Reports suggest that it can also support patients with cardiovascular diseases who suffer from hypertension. Clinical studies show that natural compounds, including cinnamon, support the process of reducing cardiovascular risk, preceded by modulation of other factors, such as oxidative stress, inflammation, hyperlipidemia, and vascular resistance .
Studies on a group of rats with seven healthy rats, seven rats with diabetes treated with probiotics, seven rats treated with cinnamon extract, and seven rats with a mixed form of treatment showed that the use of cinnamon extract added to the food reduced not only the level of blood glucose but also the level of cholesterol and triglycerides in the blood .
Cinnamon oil has also been found to be promising in the treatment of cancers, such as stomach cancer and melanoma. Cinnamaldehyde and eugenol show good results in the treatment of leukemia and lymphoma. These compounds have also been used as nutraceuticals in fighting colon and liver cancer cells .
Another interesting finding concerns the effect of cinnamon oil on hypothermia. The compounds present in the extract activate brown adipose tissue in the body. Body temperature and energy expenditure are increased by administering cinnamon extract in a cold environment. The number of mitochondria increases, and the expression of the thermogenic protein is increased. Moreover, administration of the extract alleviated damage to the heart muscle in a cold environment .
Cinnamon compounds are also applied for migraine prevention. This disease is associated with obesity. An increased body mass index is an important factor for migraine attacks. A total of 50 patients with migraines took part in a test that used treatment of this order. Half of them were the control group, and the other half received 600 mg of cinnamon. The results revealed that the inclusion of cinnamon in the diet made it possible to control weight gain and, consequently, body mass index. Daily headaches significantly decreased in these patients. These findings showed that cinnamon could be complementary in treating migraine .
Cinnamon extract is also a promising natural substance that could be incorporated into oral products to control bad breath by inhibiting the growth of Solobacterium moorei, killing the biofilm, and reducing hydrogen sulfide (H2S) production by Solobacterium moorei. Cinnamon oil in mouthwash is used as an antimicrobial agent, and it is an alternative to chlorhexidine.
Concentration of cinnamon oil has no toxic effects on oral keratinocytes, so it can be used as a daily hygiene product. Natural extracts are a complex mixture of terpenoids, phenylpropanoids, and oxygenated derivatives (aldehydes, ketones, alcohols, and esters) [67,68].
Presented in this review, the latest research findings clearly show that there is a link between the correct functioning of the human organism and nutrition, the quality of food and health, and biologically active components found in cinnamon. This information is particularly important in terms of reducing the risk of the occurrence and development of various diseases, including microcivilization diseases. In addition, the treatment of many diseases, such as diabetes, oxidative stress, and cardio disease, often requires the use of diet, which increases the effectiveness of pharmacological treatment and reduces the risk of complications.
Knowledge of biologically active substances found in cinnamon can be a link between food and medicine and can prevent diseases that are exacerbated by the course of diseases aggravated by incorrect nutrition. Moreover, knowledge of the biologically active components in cinnamon can contribute to the preparation of individualized diets based on dishes with its addition. This article also brings elements of novelty to nutrition education based on compounds contained in cinnamon, which can be used in the production of pharmaceutical preparations or dietary supplements. It also shows the correlation between consumed food products, nutrients, and human health.
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