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Cinnamon; a promising prospect towards Alzheimer’s disease
Abstract
Over the last decades, an exponential increase of efforts concerning the treatment of Alzheimer's disease (AD) has been practiced. Phytochemicals preparations have a millenary background to combat various pathological conditions. Various cinnamon species and their biologically active ingredients have renewed the interest towards the treatment of patients with mild-to-moderate AD through the inhibition of tau protein aggregation and prevention of the formation and accumulation of amyloid-β peptides into the neurotoxic oligomeric inclusions, both of which are considered to be the AD trademarks. In this review, we presented comprehensive data on the interactions of a number of cinnamon polyphenols (PPs) with oxidative stress and pro-inflammatory signaling pathways in the brain. In addition, we discussed the potential association between AD and diabetes mellitus (DM), vis-à-vis the effluence of cinnamon PPs. Further, an upcoming prospect of AD epigenetic pathophysiological conditions and cinnamon has been sighted. Data was retrieved from the scientific databases such as PubMed database of the National Library of Medicine, Scopus and Google Scholar without any time limitation. The extract of cinnamon efficiently inhibits tau accumulations, Aβ aggregation and toxicity in vivo and in vitro models. Indeed, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways. Besides, cinnamon modulates endothelial functions and attenuates the vascular cell adhesion molecules. Cinnamon PPs may induce AD epigenetic modifications. Cinnamon and in particular, cinnamaldehyde seem to be effective and safe approaches for treatment and prevention of AD onset and/or progression. However, further molecular and translational research studies as well as prolonged clinical trials are required to establish the therapeutic safety and efficacy in different cinnamon spp.
... Some evidence shows that overproduction of amyloid-β can lead to impaired memory, oxidative damage, and cognitive impairment [5,6]. So far, various plant species and plant-derived bioactive phytochemicals have been introduced with potential neuroprotective roles that can improve Alzheimer's disease and brain functions [7]. Cinnamon (Cinnamomum Verum) is a spice with a long history in different cultures. ...
... It has been considered safe according to the United States Food reactive oxygen species (ROS) [14]. Eugenol, cinnamic acid, cinnamaldehyde, syringic acid, and Catechin have antiproliferative, anti-inflammatory, and antioxidant effects [7,13,15]. Also, the components of cinnamon have potential neuroprotective effects. Also, they can play a preventive and adjuvant role in Alzheimer's disease pathogenesis [16]. ...
... It is known that cinnamon has antioxidant properties [63]. It can possess neuroprotective effects by interfering with multiple oxidative stress pathways [7]. In addition, the compound can be used to scavenge lipid peroxidation byproducts [27]. ...
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. Two thousand six hundred five studies were collected from different databases (PubMed, Scopus, Google Scholar, and Web of Science) in September 2021 and went under investigation for eligibility. As a result, 40 studies met our criteria and were included in this systematic review. Among the included studies, 33 were In vivo studies, five were In vitro, and two clinical studies were also accomplished. The main outcome of most studies (n = 40) proved that cinnamon significantly improves cognitive function (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. For clinical studies, one study showed positive effects, and another reported no changes in cognitive function. Most studies reported that cinnamon might be useful for preventing and reducing cognitive function impairment. It can be used as an adjuvant in the treatment of related diseases. However, more studies need to be done on this subject.
... Cinnamon has many different health properties that have been reported, such as its antioxidant content and its effect on diabetes and neurological, microbial, and cardiovascular diseases due to the properties of bioactive components [4]. Cinnamaldehyde is reported as a factor that decreases the production and expression of nitric oxide (NO), interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in lipopolysaccharide (LPS)-activated BV2 microglia and is therefore anti-neuroinflammatory [8]. Moreover, it has been reported to aid in neuroprotection due to its potential in inhibiting tau protein aggregation, the hallmark of Alzheimer's disease (AD) [8]. ...
... Cinnamaldehyde is reported as a factor that decreases the production and expression of nitric oxide (NO), interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in lipopolysaccharide (LPS)-activated BV2 microglia and is therefore anti-neuroinflammatory [8]. Moreover, it has been reported to aid in neuroprotection due to its potential in inhibiting tau protein aggregation, the hallmark of Alzheimer's disease (AD) [8]. Cinnamaldehyde and eugenol are responsible for protecting the gut from injury from conditions of inflammation, infections, and oxidative stress. ...
... Nowadays, it is also reported as a plant with special attributes used to treat many disorders (Figure 2). [4,8,12,13,17,37,[46][47][48][49][50][51][52][53][54][55]. ...
Cinnamon is an unusual tropical plant belonging to the Lauraceae family. It has been used for hundreds of years as a flavor additive, but it has also been used in natural Eastern medicine. Cinnamon extracts are vital oils that contain biologically active compounds, such as cinnamon aldehyde, cinnamic alcohol, cinnamic acid, and cinnamate. It has antioxidant, anti-inflammatory, and antibacterial properties and is used to treat diseases such as diabetes and cardiovascular disease. In folk medicine, cinnamon species have been used as medicine for respiratory and digestive disorders. Their potential for prophylactic and therapeutic use in Parkinson’s and Alzheimer’s disease has also been discovered. This review summarizes the available isolation methods and analytical techniques used to identify biologically active compounds present in cinnamon bark and leaves and the influence of these compounds in the treatment of disorders.
... Cinnamon is commonly used as a medicinal element in blood sugar control (Khan et al. 2003), as an antioxidant (Dugoua et al. 2007) and anti-inflammatory (Shaltiel-Karyo et al. 2012), as well as in antimicrobial activities (Ouattara et al. 1997). Recent research also suggests that the application and intake of cinnamon can have an attenuating effect on pathological conditions, such as Alzheimer's and Parkinson's diseases (Momtaz, Hassani, Khan, Ziaee, et al. 2018). ...
... The use of cinnamon, and specifically cinnamaldehyde, or larger polyphenolic fraction may be an effective and safe approach for the treatment and or prevention of the onset and/or progression of Alzheimer's disease (Momtaz, Hassani, Khan, Ziaee, et al. 2018). Other research suggests further that the application of cinnamon and its metabolite sodium benzoate helps reduce memory loss in animal models (Brahmachari et al. 2009). ...
... In this study, we propose natural substance cinnamon as a potential prophylactic treatment strategy for treating TBI. CE has been widely investigated for other neurodegenerative diseases such as Alzheimer's and Parkinson's disease and it has been shown that CE mitigated cognitive impairments (Frydman-Marom et al. 2011, Momtaz et al., 2018, b, Shaltiel-Karyo et al. 2012, Yulug et al. 2018. ...
The present paper shows how cinnamon extract (CE) consumption mitigates neuronal loss and memory impairment following traumatic brain injury (TBI), one of the world's most common neurodegenerative diseases. TBI patients suffer short- and long-term behavioral, cognitive, and emotional impairments, including difficulties in concentration, memory loss, and depression. Research shows that CE application can mitigate cognitive and behavioral impairments in animal models for Alzheimer's and Parkinson's disease, whose pathophysiology is similar to that of TBI. This study builds on prior research by showing similar results in TBI mice models. After drinking CE for a week, mice were injured using our 70-g weight drop TBI device. For 2 weeks thereafter, the mice continued drinking CE alongside standard lab nutrition. Subsequently, the mice underwent behavioral tests to assess their memory, motor activity, and anxiety. The mice brains were harvested for immunohistochemistry staining to evaluate overall neuronal survival. Our results show that CE consumption almost completely mitigates memory impairment and decreases neuronal loss after TBI. Mice that did not consume CE demonstrated impaired memory. Our results also show that CE consumption attenuated neuronal loss in the temporal cortex and the dentate gyrus. Mice that did not consume CE suffered a significant neuronal loss. There were no significant differences in anxiety levels and motor activity between all groups. These findings show a new therapeutic approach to improve cognitive function and decrease memory loss after TBI.
... Cinnamon has been used for centuries as spice with several pharmacological benefits due to the presence of polyphenolic constituent including phenolic acids, coumarin proanthocyanidin besides volatile essential oils (Momtaz et al. 2018;Wang et al. 2013). Cinnamon therapeutic application also corresponds to its antioxidant, anti-inflammatory, anti-fungal, anti-mutagenic and anticarcinogenic properties (Jayaprakasha et al. 2007;Mathew et al. 2006). ...
... Cinnamaldehyde is the main compound of the volatile oils which contribute to the aromatic smell of cinnamon. Besides its antimicrobial, antioxidant, antitumor bioactivity, cinnamaldehyde was reported to aid as neuroprotection due to its potential in inhibiting tau protein aggregation, the hallmark of Alzheimer's disease (AD) (Momtaz et al. 2018;Peterson et al. 2009;Singletary 2008). Thus, optimization of cinnamaldehyde extraction would towards AD treatments. ...
... Cinnamon extract contains polyphenolic constituents which responsible for the antioxidant properties of the extract (Momtaz et al. 2018). The antioxidant properties of cinnamon extracts were represented by TPC and TEAC showed the declination of TPC and TEAC with an increase in temperature and extraction time. ...
... In the literature, the mechanism of the protective action of phytocompounds such as resveratrol, TA, apigenin, curcumin, quercetin, etc., on the nervous system is extensively investigated and some of them are summarized in Table 2 [191][192][193][194][195][196][197][198][199][200]. Table 2. ...
... Attenuates APP expression and suppresses the levels of Aβ and β-and γ-secretase activity, decreases AChE activity and lipid peroxidation, blocks inflammatory process, increases the anti-oxidative defense system, diminish neuro-inflammatory and apoptotic pathways [196] Limonene Decreases AChE activity, reduces oxidative stress [197] Berberine Reduces Aβ levels, inhibits BACE-1 activity, decreases the hyperphosphorylation of tau. Berberine retards oxidative stress and neuroinflammation in the brain [198] Cinnamon Inhibits the formation, accumulation, and toxic effects of Aβ plaques, and has potential antioxidant effects and restoration of redox balance [199] Ginger Inhibits AChE activity, reduces Aβ levels and β-and γ-secretase activity, represses neuroinflammation and amyloid genesis, acts as a radical scavenger, prevents apoptosis [200] As can be seen from Table 2, the plant-based compounds provide therapeutic effects in AD and AD-related dementia through different mechanisms such as attenuating neuroinflammation, inhibiting AChE, delaying Aβ plaque formation, reducing and improving oxidative damage, and preventing neurotoxicity-related complications. ...
Neurodegenerative diseases occur due to progressive and sometimes irreversible loss of function and death of nerve cells. A great deal of effort is being made to understand the pathogenesis of neurodegenerative diseases. In particular, the prevalence of Alzheimer's disease (AD) is quite high, and only symptomatic therapy is available due to the absence of radical treatment. The aim of this review is to try to elucidate the general pathogenesis of AD, to provide information about the limit points of symptomatic treatment approaches, and to emphasize the potential neurologic effects of phytocompounds as new tools as therapeutic agents for disease prevention, retardation, and therapy. This survey also covers the notable properties of herbal compounds such as their effects on the inhibition of an enzyme called acetylcholinesterase, which has significant value in the treatment of AD. It has been proven that phytopharmaceuticals have long-term effects that could protect nervous system health, eliminate inflammatory responses, improve cognitive damage, provide anti-aging effects in the natural aging process, and alleviate dementia sequelae. Herbal-based therapeutic agents can afford many advantages and can be used as potentially as new-generation therapeutics or complementary agents with high compliance, fewer adverse effects, and lower cost in comparison to the traditional pharmaceutical agents in the fight against AD.
... 5% in total), and β-caryophyllene (up to 4%). Moreover, the bark contains polysaccharides (mucilage), phenolic acids (cinnamic acid and its derivatives), oligomeric proanthocyanidins, diterpenes, and others [123]. ...
... Ceylon cinnamon supplementation decreased the blood pressure of diabetes patients in clinical trials while not affecting body weight, body mass index, and waist circumference [135]. Cinnamaldehyde, found in cinnamon, has been indicated as promising and safe for the treatment or prevention of Alzheimer's disease [123]. ...
Diabetes is a metabolic disease that affected 9.3% of adults worldwide in 2019. Its co-occurrence is suspected to increase mortality from COVID-19. The treatment of diabetes is mainly based on the long-term use of pharmacological agents, often expensive and causing unpleasant side effects. There is an alarming increase in the number of pharmaceuticals taken in Europe. The aim of this paper is to concisely collect information concerning the few antidiabetic or hypoglycaemic raw plant materials that are present in the consciousness of Europeans and relatively easily accessible to them on the market and sometimes even grown on European plantations. The following raw materials are discussed in this mini-review: Morus alba L., Cinnamomum zeylanicum J.Presl, Trigonella foenum-graecum L., Phaseolus vulgaris L., Zingiber officinale Rosc., and Panax ginseng C.A.Meyer in terms of scientifically tested antidiabetic activity and the presence of characteristic biologically active compounds and their specific properties, including antioxidant properties. The characteristics of these raw materials are based on in vitro as well as in vivo studies: on animals and in clinical studies. In addition, for each plant, the possibility to use certain morphological elements in the light of EFSA legislation is given.
... In fact, silver treatment in flies [146] represents an intriguing treatment option that requires further investigation as silver is known to have opposite effects, including antiseptic activity and reduced brain inflammation as well as neurotoxicity [147,148]. Phenylpropanoid Cinnamon [135][136][137] Curcumin (1E,6E)-1,7-Bis(4hydroxy-3methoxyphenyl)hepta-1,6-diene-3,5-dione biological effects. Although the focus of this review is on recent publications using Drosophila AD models, the studies described above represent a small fraction of nutraceutical studies not only in flies, but, even in a larger number, in rodent models [122,133,134]. ...
... Although the focus of this review is on recent publications using Drosophila AD models, the studies described above represent a small fraction of nutraceutical studies not only in flies, but, even in a larger number, in rodent models [122,133,134]. For example, cinnamon and its active compound cinnamaldehyde have also shown beneficial effects on fly and mouse AD models [135][136][137]. Some additional nutraceuticals that have shown promising results ameliorating AD-related phenotypes (Table 1) include the flavonoid silybin B [138,139], curcumin [140], saffron [141], sulforaphane [142], iron [143,144] and other transition metals [145]. ...
Studies using animal models have shed light into the molecular and cellular basis for the neuropathology observed in patients with Alzheimer’s disease (AD). In particular, the role of the amyloid precursor protein (APP) plays a crucial role in the formation of senile plaques and aging-dependent degeneration. Here, we focus our review on recent findings using the Drosophila AD model to expand our understanding of APP molecular function and interactions, including insights gained from the fly homolog APP-like (APPL). Finally, as there is still no cure for AD, we review some approaches that have shown promising results in ameliorating AD-associated phenotypes, with special attention on the use of nutraceuticals and their molecular effects, as well as interactions with the gut microbiome. Overall, the phenomena described here are of fundamental significance for understanding network development and degeneration. Given the highly conserved nature of fundamental signaling pathways, the insight gained from animal models such as Drosophila melanogaster will likely advance the understanding of the mammalian brain, and thus be relevant to human health.
... The symptoms of AD depend on the stage of the disease that is classified into early-stage, mild, moderate, and late-stage according to the degree of cognitive impairment. AD is associated with neurological and motor dysfunction that ultimately results in progressive memory loss [41][42][43]. The exact cause of AD is not well understood, but oxidative damage and excessive ROS production have been characterized at the early stage of AD. ...
... TCA can increase synaptic markers in the hippocampus and frontal cortex of the mouse model of neurological disorder, indicating an improvement in synaptic connection in AD [52,56]. Besides, CA polyphenolics may improve dementia through their vasorelaxant potentials and attenuating vascular cell adhesion molecule expression within the endothelial cells [43]. These examples show that natural CA and its derivatives can improve AD symptoms by attenuating different pathological pathways. ...
Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are conducted on the effects of natural products and their active components on neurodegenerative diseases. This review will discuss an herbal constituent known as cinnamaldehyde (CA) with the neuroprotective potential to treat neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Accumulating evidence supports the notion that CA displays neuroprotective effects in AD and PD animal models by modulating neuroinflammation, suppressing oxidative stress, and improving the synaptic connection. CA exerts these effects through its action on multiple signaling pathways, including TLR4/NF-κB, NLRP3, ERK1/2-MEK, NO, and Nrf2 pathways. To summarize, CA and its derivatives have been shown to improve pathological changes in AD and PD animal models, which may provide a new therapeutic option for neurodegenerative interventions. To this end, further experimental and clinical studies are required to prove the neuroprotective effects of CA and its derivatives.
... It is one of the most important spices worldwide. Nutritional and pharmacological function of cinnamon is referred to its volatile essential oils such as cinnamate, cinnamic aldehyde, cinnamic acid, cinnamyl aldehyde , eugenol, camphor and polyphenolic composition such as Coumarins, phenolic acids, Catechin , epigallocatechin gallate (EGCG), terpenes and tannins that mostly responsible for its antioxidant potential 6 . These products recorded a potent effect in reducing oxidative stress according to doses by inhibiting of 5-lipoxygenase enzyme 7 .Furthermore cinnamon bioactive compounds have potent therapeutic efficiency in diabetes mellitus 7 , cardiovascular disease 8 , cancer 9 , inflammatory syndromes, cholesterol levels, wound healing 10 and immune-modulatory diseases 11 . ...
... These products recorded a potent effect in reducing oxidative stress according to doses by inhibiting of 5-lipoxygenase enzyme 7 .Furthermore cinnamon bioactive compounds have potent therapeutic efficiency in diabetes mellitus 7 , cardiovascular disease 8 , cancer 9 , inflammatory syndromes, cholesterol levels, wound healing 10 and immune-modulatory diseases 11 . As well as, cinnamon was being used traditionally for centuries because of their carminative, neuronstimulant, antifungal and antibacterial properties 6 . Although the anti-inflammatory effects of cinnamon extract was reported in many studies [12][13][14] , its possible effects on tissue antioxidant status and inflammation in gastric ulcer status have not been studied. ...
Abstract: Peptic ulcer disease is a break in inner layer of the stomach and/or first part of the small intestine. It‟s mostly caused by bacterial infection of Helicobacter pylori or drug induced as non-steroidal anti-inflammatory drugs. The present study was conducted to test the hypothesis that aqueous cinnamon extract (CE) has anti-inflammatory effect as well as antioxidant activity on ethanol induced gastric ulcer in rats. The present study was developed in wister albino rats at dosing 250 & 500 mg/kg P.O. comparing their effects with ranitidine, a standard antiulcer medication. After scarifying the animals, blood samples were collected for biomedical analysis, the stomach were cut and open to determine gastric PH and for measuring ulcer index. Pretreatment of rats with 500 mg/kg cinnamon extract neutralize the elevated level of ulcer index and Hcl content of the stomach caused by ingestion of ethanol even better than the effect caused by 250 mg/kg cinnamon and ranitidine, also decrease level of NF-ҡB, increase level of TGF- β1, level of NO & MDA were significantly decrease and level of PONI & GSH compared with ethanol treated group. Treatment of peptic ulcer with cinnamon extract has potent antiulcer effect comparable to that exerted by ranitidine, standard antiulcer medication.
... It is one of the most important spices worldwide. Nutritional and pharmacological function of cinnamon is referred to its volatile essential oils such as cinnamate, cinnamic aldehyde, cinnamic acid, cinnamyl aldehyde , eugenol, camphor and polyphenolic composition such as Coumarins, phenolic acids, Catechin , epigallocatechin gallate (EGCG), terpenes and tannins that mostly responsible for its antioxidant potential 6 . These products recorded a potent effect in reducing oxidative stress according to doses by inhibiting of 5-lipoxygenase enzyme 7 .Furthermore cinnamon bioactive compounds have potent therapeutic efficiency in diabetes mellitus 7 , cardiovascular disease 8 , cancer 9 , inflammatory syndromes, cholesterol levels, wound healing 10 and immune-modulatory diseases 11 . ...
... These products recorded a potent effect in reducing oxidative stress according to doses by inhibiting of 5-lipoxygenase enzyme 7 .Furthermore cinnamon bioactive compounds have potent therapeutic efficiency in diabetes mellitus 7 , cardiovascular disease 8 , cancer 9 , inflammatory syndromes, cholesterol levels, wound healing 10 and immune-modulatory diseases 11 . As well as, cinnamon was being used traditionally for centuries because of their carminative, neuronstimulant, antifungal and antibacterial properties 6 . Although the anti-inflammatory effects of cinnamon extract was reported in many studies [12][13][14] , its possible effects on tissue antioxidant status and inflammation in gastric ulcer status have not been studied. ...
Abstract: Peptic ulcer disease is a break in inner layer of the stomach and/or first part of the small intestine. It‟s mostly caused by bacterial infection of Helicobacter pylori or drug induced as non-steroidal anti-inflammatory drugs. The present study was conducted to test the hypothesis that aqueous cinnamon extract (CE) has anti-inflammatory effect as well as antioxidant activity on ethanol induced gastric ulcer in rats. The present study was developed in wister albino rats at dosing 250 & 500 mg/kg P.O. comparing their effects with ranitidine, a standard antiulcer medication. After scarifying the animals, blood samples were collected for biomedical analysis, the stomach were cut and open to determine gastric PH and for measuring ulcer index. Pretreatment of rats with 500 mg/kg cinnamon extract neutralize the elevated level of ulcer index and Hcl content of the stomach caused by ingestion of ethanol even better than the effect caused by 250 mg/kg cinnamon and ranitidine, also decrease level of NF-ҡB, increase level of TGF- β1, level of NO & MDA were significantly decrease and level of PONI & GSH compared with ethanol treated group. Treatment of peptic ulcer with cinnamon extract has potent antiulcer effect comparable to that exerted by ranitidine, standard antiulcer medication.
... In AD, oxidative impairment is generally derived from mitochondrial dysfunction and microglial activation (the formation of ROS and NOS), thereby provoking calcium overload and excitotoxicity and eventually leading to neuronal apoptosis (Cenini et al. 2019). Cinnamon exerts its neuroprotective effects by interfering with oxidative stress, calcium overload, proinflammatory pathways, and tau aggregation and has been shown to ameliorate Alzheimer's disease progression in in vitro and in vivo models (Momtaz et al. 2018). Cinnamon inhibited the formation, accumulation, and toxic effects of Aβ plaques in PC12 neuronal cells. ...
Healthy ageing and longevity in humans are determined by a combination of genetic and non-genetic factors. To attain longevity, interventions that modulate the interaction between genetic background and the environment and/or lifestyle are essential. Apolipoprotein E (APOE) ε4 allelic variant is recognized as a longevity determinant genetic polymorphism in different ethnic populations, probably through its associations with various pathological conditions such as Alzheimer’s disease (AD) and atherosclerosis. Melatonin, a pineal hormone which decreases with ageing, has various physiological functions in the brain, including regulation of circadian rhythms, clearance of free radicals, inhibition of biomolecular oxidation, suppression of neuroinflammation, and neuroprotection. There is a strong association between sleep quality and memory consolidation, and the diminished production of melatonin which is a physiological regulator of sleep–wake cycle has been demonstrated in ageing diseases including AD. Nutritional factors could have an impact on healthy ageing as diets that are rich in natural products that contain high amounts of plant bioactive molecules including polyphenols, antioxidant vitamins, and melatonin which are promising dietary strategies in preventing chronic diseases and ensuring healthy ageing.
... With this technique, several lead candidates against Aβ aggregation have been found by screening vast libraries of synthetic and natural chemicals. Natural compound-based molecules of curcumin [21][22][23], catechol [24], polyphenol, epigallocatechin-3-gallate [25], and cinnamon [26] were examined and found to be effective in reducing the Aβ plaques in the brain through their antioxidant and antiaggregation properties [27]. Structural alteration of natural substances, such as curcumin [28] and resveratrol [29], gave highly effective modulation [30] of Aβ aggregation by controlling the harmful oligomeric formation through inhibiting hydrophobic interactions [31]. ...
In this investigation, a number of phenoxyindole derivatives were designed, synthesized, and tested for their neuroprotective ability on SK-N-SH cells against Aβ42-induced cell death and biologically specific activities involved in anti-Aβ aggregation, anti-AChE, and antioxidant effects. The proposed compounds, except compounds 9 and 10, could protect SK-N-SH cells at the IC50 of anti-Aβ aggregation with cell viability values ranging from 63.05% ± 2.70% to 87.90% ± 3.26%. Compounds 3, 5, and 8 demonstrated striking relationships between the %viability of SK-N-SH cells and IC50 values of anti-Aβ aggregation and antioxidants. No significant potency of all synthesized compounds against AChE was found. Among them, compound 5 showed the strongest anti-Aβ and antioxidant properties with IC50 values of 3.18 ± 0.87 and 28.18 ± 1.40 μM, respectively. The docking data on the monomeric Aβ peptide of compound 5 demonstrated good binding at regions involved in the aggregation process, and the structural feature made it possible to be a superior radical scavenger. The most effective neuroprotectant belonged to compound 8, with a cell viability value of 87.90% ± 3.26%. Its unique mechanisms for enhancing the protective impact may serve additional purposes since it demonstrated mild biological-specific effects. In silico prediction of CNS penetration shows strong passive penetration ability across the blood–brain barrier from blood vessels to the CNS for compound 8. In light of our findings, compounds 5 and 8 appeared as potentially intriguing lead compounds for new therapeutic approaches to Alzheimer’s disease. More in vivo testing will be revealed in due course.
... The anticancer capability of ginger and its derivatives has been extensively investigated. These studies have elaborated the efficacy in (i) directly killing cancer cells; (ii) combining therapy with clinical drugs to reduce the dosage of these drugs and subsequent side-effect elicitation; (iii) lowering the occurrence of drug resistance [22][23][24][25][26][27]. Recently, a new report proposed that 6-shogaol antagonizes the survival of HNSCC cells [20]. ...
Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.
... Cinnamon is broadly used as a fragrance additive in daily chemical and dietary supplement industries [13,14]. Of note, cinnamon has obtained a lot of attention in recent years, due to its stated health benefits [12,24]. It is documented that the volatile essential oils, the major source of CA, are mainly isolated from the dried stem bark of cinnamon, owing that this segment contains the highest content of oils in the plant, up to 2.5% of bark weight [14,25]. ...
Evidence from epidemiological studies has demonstrated that the incidence and mortality of cardiovascular diseases (CVDs) increase year by year, which pose a great threat on social economy and human health worldwide. Due to limited therapeutic benefits and associated adverse effects of current medications, there is an urgent need to uncover novel agents with favorable safety and efficacy. Cinnamaldehyde (CA) is a bioactive phytochemical isolated from the stem bark of Chinese herbal medicine Cinnamon and has been suggested to possess curative roles against the development of CVDs. This integrated review intends to summarize the physicochemical and pharmacokinetic features of CA and discuss the recent advances in underlying mechanisms and potential targets responsible for anti-CVD properties of CA. The CA-related cardiovascular protective mechanisms could be attributed to the inhibition of inflammation and oxidative stress, improvement of lipid and glucose metabolism, regulation of cell proliferation and apoptosis, suppression of cardiac fibrosis, and platelet aggregation and promotion of vasodilation and angiogenesis. Furthermore, CA is likely to inhibit CVD progression via affecting other possible processes including autophagy and ER stress regulation, gut microbiota and immune homeostasis, ion metabolism, ncRNA expression, and TRPA1 activation. Collectively, experiments reported previously highlight the therapeutic effects of CA and clinical trials are advocated to offer scientific basis for the compound future applied in clinical practice for CVD prophylaxis and treatment.
... Molecular conditions like this have enormous potential to be modified to increase their activity as medicinal raw materials (Suryanti et al., 2018). Among the CD-derived compounds modified at the base skeleton of the benzene ring, the compound 2-hydroxycinamaldehyde (HC) have the best bioactivity in various field as an anti-fungal (Shreaz et al., 2016), antibacterial (Momtaz et al., 2018), antitumor (Lee et al., 2013), anticancer (Hwang et al., 2011;Larasati & Meiyanto, 2018), and many other benefits. HC was obtained from the isolation of natural ingredients from cinnamon bark oil (Kwon et al., 1996). ...
Cinnamaldehyde is the major secondary metabolite of Cinnamon (Cinnamomum burmanii) that has various benefits in medical fields. One of the cinnamaldehyde derivatives, 2-Hydroxycinnamaldehyde (HC), has been shown to have good anticancer activity. In contrast to its activity, the synthesis method of HC from pure cinnamaldehyde has not been studied before. This research studies the synthesis of HC with a semisynthetic approach from the natural ingredient cinnamaldehyde. This study was initiated by purifying cinnamaldehyde from cinnamon bark oil with the salting method using a saturated sodium bisulfite solution. Cinnamaldehyde is converted into HC through the synthesis design in three-reaction steps, including nitration using nitric acid-acetic acid anhydride at 0-5 °C, reduction in mild condition by reflux using NH4Cl-Fe in methanol-water solution, and diazotation-hydrolysis using NaNO2-HCl at 5 °C. Optimization of the synthesis was evaluated to get the best method according to yield and characterized using TLC, UV-Vis, FTIR, and GC-MS/LC-MS. The isolated CD has a purity of up to 100% with a yield of about 36%. The 2-nitrocinnamaldehyde (NC) product from nitration was analyzed with ethanol and n-hexane (1:1) Rf = 0.84 and showed high purity with a 26% yield. The reduction product 2-aminocinnamaldehyde (Rf = 0.48) and 2-hydroxycinamaldehyde (Rf = 0.19) as a product from diazotation-hydrolysis obtained in moderate yield.
... The predominant bioactive constituents in ginger are gingerols, shagols, bisabolene, zingiberene, and monoterpenes . White and red ginger were tested for their ability to inactivate AChE and were measured using colorimetric analysis (Momtaz et al., 2018). Ginger extract has an inhibitory potential on AChE, particularly white ginger which displays a strong impact. ...
The current scientific community is facing a daunting challenge to unravel reliable natural compounds with realistic potential to treat neurological disorders such as Alzheimer’s disease (AD). The reported compounds/drugs mostly synthetic deemed the reliability and therapeutic potential largely due to their complexity and off-target issues. The natural products from nutraceutical compounds emerge as viable preventive therapeutics to fill the huge gap in treating neurological disorders. Considering that Alzheimer’s disease is a multifactorial disease, natural compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs so far used to treat Alzheimer’s disease. A wide range of plant extracts and phytochemicals reported to possess the therapeutic potential to Alzheimer’s disease includes curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and other phytochemicals such as huperzine A, limonoids, and azaphilones. Reported targets of these natural compounds include inhibition of acetylcholinesterase, amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc. We tenaciously aimed to review the in-depth potential of natural products and their therapeutic applications against Alzheimer’s disease, with a special focus on a diversity of medicinal plants and phytocompounds and their mechanism of action against Alzheimer’s disease pathologies. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against Alzheimer’s disease with lesser side effects as compared to currently available treatments.
... 34 Furthermore, cinnamon and its polyphenolic constituents interfere with AD progress through suppressing pro-inflammatory pathways and mediators 35 , regulating endothelial integrity and function 36 , and probably AD-related epigenetic alterations. 37 In another study oral feeding of cinnamon powder and sodium benzoate (NaB) suppressed the activation of p21rac geranylgeranyl protein and extenuated oxidative stress in the hippocampus of transgenic mice as evident by decreased dihydroethidium (DHE) and nitrotyrosine staining, reduced homocysteine level and increased level of decreased glutathione. This led to suppression of neuronal apoptosis, inhibition of glial activation, and reduction of Aβ burden in the hippocampus and protection of memory and learning in transgenic mice. ...
An increasing amount of evidence suggests that cinnamon, due to its rich source of polyphenol content, may exert antioxidant and anti-inflammatory properties, hence could be used in the treatment of variety of diseases. in this regard, many studies explored the effects of cinnamon and its bioactive components (coumarin, cinnamic acid, cinnamaldehyde and type A procyanidin polymers) on various neurological diseases including Parkinson’s disease, neuroinflammation, multiple sclerosis, brain injury, Alzheimer’s disease, migraine, and hyperactivity. The present study attempts to review available data concerning the therapeutic potential of cinnamon and its derivatives in neurological disorders.
... The Cinnamomum genus encompasses about 250 species, and several of them have been used as spices for centuries (21,22). Cinnamon used in seasoning material consists of dried inner bark of trees from the genus. ...
Cinnamic acid (AC) and cinnamic aldehyde (AL) are two chemicals enriched in cinnamon and have been previously proved to improve glucolipid metabolism, thus ameliorating metabolic disorders. In this study, we employed transcriptomes and proteomes on AC and AL treated db/db mice in order to explore the underlying mechanisms for their effects. Db/db mice were divided into three groups: the control group, AC group and AL group. Gender- and age-matched wt / wt mice were used as a normal group. After 4 weeks of treatments, mice were sacrificed, and liver tissues were used for further analyses. Functional enrichment of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. DEPs were further verified by parallel reaction monitoring (PRM). The results suggested that AC and AL share similar mechanisms, and they may improve glucolipid metabolism by improving mitochondrial functions, decreasing serotonin contents and upregulating autophagy mediated lipid clearance. This study provides an insight into the molecular mechanisms of AC and AL on hepatic transcriptomes and proteomes in disrupted metabolic situations and lays a foundation for future experiments.
... It has been recommended that the capacity of cinnamon flavonoids and its metabolites to enter the brain upon crossing the BBB mostly depends on the extent of their lipophilicity (Lin et al. 2007). Despite this fact, there are certain animal studies which show the entry of glucuronides into the brain through BBB (Momtaz et al. 2018). ...
Cinnamon
Botany, Agronomy, Chemistry and
Industrial Applications
... There have been many benefits claimed in the literature and a few extended into phase I and II clinical trials. The list includes (1) lowering of blood glucose(Akilen et al., 2010(Akilen et al., , 2013Crawford et al., 2016;Davis & Yokoyama, 2011;Ranasinghe et al., 2017;Zhu et al., 2017); (2) blood pressure control(Akilen et al., 2010(Akilen et al., , 2013Azimi et al., 2016); (3) lowering of serum cholesterol(Chatterji & Fogel, 2018;Gupta et al., 2017;Maierean et al., 2017); (4) antimicrobial activity(Condo et al., 2018;Husain et al., 2018;Mamajiwala et al., 2018;Rangel et al., 2018;Raybaudi-Massilia et al., 2006;Sethi et al., 2019;Shahina et al., 2018); (5) antiparasitic activity(Yang et al., 2014); (6) antioxidative properties and related free radical scavenging action(Dhuley, 1999;Khaki et al., 2014;Panickar et al., 2009;Ranasinghe et al., 2013;Shahid et al., 2018;Sharma et al., 2017);(7) prevention of aggregates and filament formation in Alzheimer's disease (AD)(Kang et al., 2016;Madhavadas & Subramanian, 2017;Malik et al., 2015;Momtaz et al., 2018); (8) gastritis and antigastric ulcer effects(Muhammad et al., 2015;Nir et al., 2000); (9) inhibition of osteoclastogenesis(Mendi et al., 2017;Tsuji-Naito, 2008);(10) anti-inflammatory (Fayaz et al., 2019; Ose et al., 2019; Schink et al., 2018); (11) wound healing and dressings (Ahmed et al., 2019; Ferro et al., 2019; Seyed Ahmadi et al., 2019), and more recently, promise for use in wound care practices (Ahmed et al., 2020); ...
Cinnamomum zeylanicum (“Ceylon cinnamon/true cinnamon”) is native to Sri Lanka. In addition to generating significant foreign income, over 350,000 families are involved in the cinnamon industry, demonstrating its long‐established role in the Sri Lankan society. The spice constitutes many bioactive compounds with antioxidant, antimicrobial, and insecticidal properties, in addition to therapeutic and preventive effects against many diseases and disorders. New uses of cinnamon continue to emerge, and in this review, we discuss the opportunities for crop and product improvement, which will likely impact positively on the lives and livelihood of the population in Sri Lanka. Cinnamomum zeylanicum Blume, known as Ceylon cinnamon, is native to Sri Lanka, whereas Cinnamomum cassia J. Presl (Cassia cinnamon) and other types of Cinnamomum spp. are grown in China and many other parts of Asia. Ceylon cinnamon is relatively expensive due to its chemical composition, high quality, proven health benefits, and ultra‐low levels of the toxic chemical compound, coumarin, which is reported in comparatively high concentrations in Cassia cinnamon. In Sri Lanka, more than 350,000 families are involved in the cinnamon industry. Among the total agricultural produce of Sri Lanka, cinnamon exports provide the second highest in terms of income (second only to tea). In addition to the use of cinnamon as a spice, leaf and bark extracts are used in the food industry to (a) improve the postharvest life of perishable foods through antimicrobial activity and (b) control pests in postharvest storage (insecticidal activity). The human health benefits include antioxidant activity and therapeutic and preventative properties against diseases and disorders. The potential uses of Ceylon cinnamon in the global food industry, health, and cosmetics sectors are abundant. However, to ensure maximum benefits to producers and consumers, accredited laboratory testing and legislative procedures need to be developed and strengthened to detect and reduce malpractice and product adulteration in the global marketplace. There are also considerable opportunities for crop improvement. The application of contemporary genomic and genetic approaches coupled to plant breeding will be needed to improve yields and disease resistance and to safeguard production in the face of the threats posed by global environmental change. Cinnamomum zeylanicum (“Ceylon cinnamon/true cinnamon”) is native to Sri Lanka. In addition to generating significant foreign income, over 350,000 families are involved in the cinnamon industry, demonstrating its long‐established role in the Sri Lankan society. The spice constitutes many bioactive compounds with antioxidant, antimicrobial, and insecticidal properties, in addition to therapeutic and preventive effects against many diseases and disorders. New uses of cinnamon continue to emerge, and in this review, we discuss the opportunities for crop and product improvement, which will likely impact positively on the lives and livelihood of the population in Sri Lanka.
... It has been recommended that the capacity of cinnamon flavonoids and its metabolites to enter the brain upon crossing the BBB mostly depends on the extent of their lipophilicity (Lin et al. 2007). Despite this fact, there are certain animal studies which show the entry of glucuronides into the brain through BBB (Momtaz et al. 2018). ...
Sri Lanka is the market leader of Ceylon cinnamon with a 90% global market share. Cinnamon is one of the leading foreign exchange earners from among agricultural exports of Sri Lanka. The cinnamon extent of cultivation, production, and yield has only marginally increased over the past few decades despite high potential in the global market. However, the major competitive product cassia produced and exported predominantly by Indonesia, China, and Vietnam has contributed to the erosion of Ceylon cinnamon market share, notwithstanding warning from leading health agencies about its negative impact on health due to high content of coumarin. Ceylon cinnamon has the potential to become Sri Lanka’s number one foreign exchange earner from the agriculture sector by building on its competitive edge as the main true cinnamon supplier. Product and process innovation with a focus on compliance with food safety and quality requirements remains the most feasible and practical option to exploit the competitive edge of Ceylon cinnamon in the global marketplace. Marketing strategies should focus on product diversification, value addition, and brand recognition.
... Curcumin regulates the signal transduction pathway involved in NOS-mediated neurotoxicity and has a protective effect on quinolinic acid-induced neurotoxicity, and prevents Ab aggregation and oligomer formation (Essa et al., 2012b). Cinnamon extracts (cinnamaldehyde, eugenol, cinnamyl acetate and cinnamyl alcohol) also have the ability to prevent the formation of oligomers and amyloid fibrils (Momtaz et al., 2018;Pham et al., 2018). Sinapinic acid and alkaloids such as berberine, caffeine can effectively inhibit acetylcholinesterase in vitro and in brain tissue (Williams et al., 2011b;Ji and Shen, 2011). ...
Phytochemicals refer to active substances in plant-based diets. Phytochemicals found in for example fruits, vegetables, grains and seed oils are considered relatively safe for consumption due to mammal-plant co-evolution and adaptation. A number of human diseases are related to oxidative stress caused by for example chemical environmental contaminants in air, water and food; while also lifestyle including smoking and lack of exercise and dietary preferences are important factors for disease development in humans. Here we explore the dietary sources of antioxidant phytochemicals that have beneficial effects on oxidative stress, cardiovascular and neurological diseases as well as cancer. Plant-based diets usually contain phenolic acids, flavonoids and carotenoids, which have strong antioxidant properties, and therefore remove the excess of active oxygen in the body, and protect cells from damage, reducing the risk of cardiovascular and Alzheimer’s disease. In most cases, obesity is related to diet and inactivity and plant-based diets change lipid composition and metabolism, which reduce obesity related hazards. Cruciferous and Allium vegetables are rich in organic sulphides that can act on the metabolism of carcinogens and therefore used as anti-cancer and suppressing agents while dietary fibres and plant sterols may improve intestinal health and prevent intestinal diseases. Thus, we recommend a diet rich in fruits, vegetables, and grains as its content of phytochemicals may have the potential to prevent or improve a broad sweep of various diseases.
... Previous studies revealed that cinnamon treatment down-regulate the iNOS gene in the mouse model (Khasnavis and Pahan, 2014). Trans-cinnamaldehydesignificantly reduced the production of nitric oxide and the expression of iNOS mRNA (Chen et al., 2016;Momtaz et al., 2018). ...
The objective of this study was to investigate the influence of deltamethrin (DLM)on brain function and to find whether DLM-induced neurotoxicity is prevented by the treatment with cinnamon oil. Four groups of ten Wistar albino male rats each were used. Group I (control) received saline only. Group II received cinnamon oil alone at 0.5 mg/kg B.W. intraperitonally, whereas Group III received orally DLM alone at 6 mg/kg B.W. Groups IV was treated with cinnamon oil plus DLM for 21 days to induce neurotoxicity. Rat behaviour, brain acetylcholine esterase (AChE), serotonin, oxidative stress profile were assessed. Serum sampling for the assessment of corticosterone concentration was also carried out. Finally, we demonstrate the gene expression of CYP1A1 and iNOS and the histological picture of the brain. Considering the behaviour assessment, DLM administration alone caused neurobehavioral deficits manifested by anxiety-like behavior which represented ina marked decrease in the sleeping frequency and duration, and marked increase the digging frequency and a wake non-active behavior duration. Moreover, the open field result showed a significant decrease in central square entries and duration. The neurochemical analysis revealed that DLM significantly suppressed AChE activity and elevated serotonin and corticosterone concentrations. Furthermore, results revealed thatthe brain reduced glutathione (GSH) content, superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were significantly altered in DLM treated rats. Neurochemical disturbances were confirmed by histopathological changes in the brain. Furthermore, DLM up-regulates the mRNA expression of brain CYP1A1 and iNOS. Co-treatment with cinnamon oil exhibited significant improvement in behavioural performance and the brain antioxidant capacities with an increase in AChE activity and diminished the concentration of serotonin, serum corticosterone and MDA. Cinnamon oil treatment resulted in down-regulation of CYP1A1 and iNOS and improve the histologically picture. In conclusion, cinnamon oil ameliorated DLM-induced neurotoxicity through preventing oxidative stress-induced genotoxicity and apoptosis of brain in rats.
... CUR, known to reduce the Aβ production by inhibiting glycogen synthase kinase 3-β-mediated PSEN1 activation, inhibits HDAC isoforms 1, 3 and 8, thus participating in reprogramming neural stem cell-directed neurogenesis [348]. It also inhibits HATs [387]. However, besides CUR, little is known about dietary modulation of HAT activity. ...
A new epoch is emerging with intense research on nutraceuticals, i.e., “food or food product that provides medical or health benefits including the prevention and treatment of diseases”, such as Alzheimer’s disease. Nutraceuticals act at different biochemical and metabolic levels and much evidence shows their neuroprotective effects; in particular, they are able to provide protection against mitochondrial damage, oxidative stress, toxicity of β-amyloid and Tau and cell death. They have been shown to influence the composition of the intestinal microbiota significantly contributing to the discovery that differential microorganisms composition is associated with the formation and aggregation of cerebral toxic proteins. Further, the routes of interaction between epigenetic mechanisms and the microbiota–gut–brain axis have been elucidated, thus establishing a modulatory role of diet-induced epigenetic changes of gut microbiota in shaping the brain. This review examines recent scientific literature addressing the beneficial effects of some natural products for which mechanistic evidence to prevent or slowdown AD are available. Even if the road is still long, the results are already exceptional.
... Epidemiologically, the prevalence of Alzheimer's disease (AD) is about 50 million people world-wide. This number is expected to augment by 3 folds in the coming 30 years 1 . The global social expenses have been increased to US$1 trillion in 2018 2 . ...
Background
The global social expenses of Alzheimer's disease (AD) have been increased to US$1 trillion due to high cost, side-effects, and low efficiency of the current AD-therapies. Another reason is the lack of preventive drugs and the low-income situation of Asian and African countries. Accordingly, patients rather prefer traditional herbal remedies. Network-pharmacology has been a well-established method for the visualization and the construction of disorder target protein-drug framework. This could aid in the identification of drugs molecular-mechanisms.
Aim
The aim of this study is to investigate the phytochemical constituents that could target Alzheimer's disease from the North African plants. This could be done by exploring their possible mechanisms of action through molecular network pharmacology-based approach.
Experimental procedure
The Phytochemical-compounds of North-African plants (NAP) have been accessed from open-databank. ADME-screening has been conducted for filtering of the NAP phytochemical-constituents utilizing Qikprop-software. The open STITCH databank has been utilized for the prediction of the phytochemical-constituents target-proteins; UniProt and TDD-DB databanks have been utilized for distinguishing AD-related proteins. Phytochemical constituent-target protein (C-T) and plant-phytochemical constituent-target protein (P-C-T) frameworks have been assembled utilizing Cytoscape to interpret the anti-Alzheimer's disease mechanism of action of the targeted phytochemical constituents.
Results
The NAP 6842 phytochemical-constituents (from more than 1000 plants) have been exposed to ADME and CNS modulating filtration, generating 94 phytochemical-constituents which have been subjected to target-prediction investigation. The 94 phytochemical-constituents and the 4 AD-identified targets have been associated through 155 edges which formed the main pathways related to AD. Cuparene, alpha-selinene, beta-sesquiphellandrene, calamenene, 2-4-dimethylheptane, undecane, n-tetradecane, hexadecane, nonadecane, n-eicosane, and heneicosane have had C-T network highest combined-score, whilst the proteins MAO-B, HMG-CoA, BACE1, and GCR have been the most enriched ones by comprising the uppermost combined-scores of C-T. Hypericum perforatum, Piper nigrum, Juniperus communis, Levisticum officinale, Origanum vulgare acquired the uppermost number of P-C-Target interactions.
Conclusion
The phytochemical-targets prediction of NAP utilizing molecular-network pharmacology-based investigation has paved the way for networking multi-target, multi-constituent, and multi-pathway mechanisms. This may introduce potential future targets for the regulation and the management of Alzheimer's disease.
Taxonomy (classification by EVISE)
Alzheimer's disease, Network pharmacology, In-silico computer based approach
... Cinnamomi Ramulus (the twig of Cinnamomum cassia Blume; Lauraceae) and Paeoniae Radix (the root of Paeonia lactiflora Pallas; Paeoniaceae) have been shown to exert efficacy in inhibiting the formation of AGEs in our previous study. Cinnamomi Ramulus has traditionally been used for its anti-inflammatory, antioxidant, and neuroinflammatory effects [15]. Its marker compounds include coumarin, cinnamyl alcohol, and cinnamic acid. ...
Increased formation of advanced glycation end products (AGEs) plays an important role in the development of diabetic retinopathy (DR) via blood-retinal barrier (BRB) dysfunction, and reduction of AGEs has been suggested as a therapeutic target for DR. In this study, we examined whether CPA4-1, a herbal combination of Cinnamomi Ramulus and Paeoniae Radix, inhibits AGE formation. CPA4-1 and fenofibrate were tested to ameliorate changes in retinal capillaries and retinal occludin expression in db/db mice, a mouse model of obesity-induced type 2 diabetes. CPA4-1 (100 mg/kg) or fenofibrate (100 mg/kg) were orally administered once a day for 12 weeks. CPA4-1 ( the half maximal inhibitory concentration, IC50 = 6.84 ± 0.08 μg/mL) showed approximately 11.44-fold higher inhibitory effect on AGE formation than that of aminoguanidine (AG, the inhibitor of AGEs, IC50 = 78.28 ± 4.24 μg/mL), as well as breaking effect on AGE-bovine serum albumin crosslinking with collagen (IC50 = 1.30 ± 0.37 μg/mL). CPA4-1 treatment ameliorated BRB leakage and tended to increase retinal occludin expression in db/db mice. CPA4-1 or fenofibrate treatment significantly reduced retinal acellular capillary formation in db/db mice. These findings suggested the potential of CPA4-1 as a therapeutic supplement for protection against retinal vascular permeability diseases.
... Studies have shown that CZ increases neuronal survival by rebalancing the redox state and suppressing neuroinflammation. Therefore, targeting the hallmarks of AD can improve both histopathological and behavioral outcomes in different animal models (Momtaz et al., 2018;Madhavadas et al., 2017;Modi et al., 2015;George et al., 2013;Jana et al., 2013;Frydman-Marom et al., 2011) and in vitro (Peterson et al., 2009). With this background in mind, the present study aimed to investigate the effect of methanolic extract of CZ bark on the hippocampal phospho-tau, inflammatory cytokines, nuclear damage, and spatial memory of FAtreated rats. ...
Accumulation of formaldehyde (FA) in the brain is linked to age-related neurodegenerative disorders, as it accelerates memory impairment through tau protein aggregation, inflammation, and nuclear damage. This study aimed to assess the possible effects of methanolic cinnamon extract (CE) on FA-induced neurotoxicity in rats. The animals were treated with CE (100, 200, and 400 mg/kg, P.O.) for 30 days following FA administration (60 mg/kg, I.P.) for 30 days. Briefly, spatial and inhibitory memory were examined by Morris water maze (MWM) and passive avoidance (PA) tasks, respectively. The Nissl, Hoechst, and Bielschowsky silver staining methods were also used to assess apoptosis and neurofibrillary tangles (NFTs) in the hippocampal CA1 region, respectively. Brain tissues were probed with an anti-phospho-tau (Thr 231) monoclonal antibody to assess tau hyperphosphorylation. Inflam-matory cytokines (IL-1β, IL-6, and TNF-α) were also measured by ELISA assay. Western blotting was performed to quantify the amount of phospho-tau (Thr 231), caspase-8, and caspase-9. The results showed that FA injection significantly caused tau hyperphosphorylation at Thr 231 residue, which in turn disturbed the MWM performance. The ratio of apoptotic to intact neurons increased following FA treatment. The results of Western blotting indicated that the hippocampal levels of phospho-tau (Thr 231) and caspase-8 were significantly higher in the FA group compared to the control group. The hippocampal levels of IL-1β, IL-6, and TNF-α in the FA group were also higher than the control group. Administration of 200 mg/kg of CE significantly improved the rats' MWM performance, decreased the levels of phospho-tau (Thr 231), caspase-8, IL-6, and TNF-α, and reduced the ratio of apoptotic to intact neurons. Overall, cinnamon improved cognitive performance in FA-treated rats by eliminating tau hyper-phosphorylation, inflammatory cytokines, and nuclear damage.
... The β-amyloid induces neuronal cell death through disrupting their communications at synapses, while tau tangles contribute to neuronal cell death by blocking the entry of nutrients and other essential molecules into the neurons. Gradual increase of β-amyloid plaques outside the neurons results in consequent spreading of tau tangles throughout neurons (De Paula et al., 2009;Penke et al., 2017;Momtaz et al., 2018). ...
Nanotechnology is one of the methods that influenced human life in different ways and is a substantial approach that assists to overcome the multiple limitations of various diseases, particularly neurodegenerative disorders (NDs). Diverse nanostructures such as polymer nanoparticles, lipid nanoparticles, nanoliposomes, nano-micelles, and carbon nanotubes (CNTs); as well as different vehicle systems including poly lactic-co-glycolic acid, lactoferrin, and polybutylcyanoacrylate could significantly increase the effectiveness, reduce the side effects, enhance the stability, and improve the pharmacokinetics of many drugs. NDs belong to a group of annoying and debilitating diseases that involve millions of people worldwide. Previous studies revealed that several nanoformulations from a number of natural products such as curcumin (Cur), quercetin (QC), resveratrol (RSV), piperine (PIP), Ginkgo biloba, and Nigella sativa significantly improved the condition of patients diagnosed with NDs. Drug delivery to the central nervous system (CNS) has several limitations, in which the blood brain barrier (BBB) is the main drawback for treatment of NDs. This review discusses the effects of herbal-based nanoformulations, their advantages and disadvantages, to manage NDs. In summary, we conclude that herbal-based nano systems have promising proficiency in treatment of NDs, either alone or in combination with other drugs.
... Since 1-2% of the populations older than 65 years and up to 3-5% of people aged over 85 years suffer from PD [31], using novel approaches such as plant-derived preparations beside conventional treatment may potentiate the protective or therapeutic benefits to prevent or diminish adverse pathological effects of PD [32]. Cinnamaldehyde is a widely-investigated cinnamon product that possesses neuroprotective effects [33]. Here, we have evaluated and compared the protective effects of extracts and essential oils of C. verum and C. cassia and cinnamaldehyde on 6-OHDAinduced apoptosis in PC12 cells as an in vitro PD model. ...
Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p < 0.001), and decrease ROS content (p < 0.05). Pretreatment with the extracts increased survivin and decreased cyt-c whereas, pretreatment with the essential oil decreased cyt-c, increased survivin, and reduced P-p44/42/p44/42 levels to a level near that of the related control. The extract and essential oil of C. verum and C. cassia can be effective against 6-OHDA cytotoxicity. It is suggested that, the synergistic effects of cinnamaldehyde and other components of extract and essential oil promote cinnamon’s medicinal properties.
... The antibacterial activity of CEO was tested by Liesel, Gende, Floris, Fritz and Eguaras [8]. In recent years, CEO has been widely used in the food, pharmaceutical, textile and cosmetic industries [9][10][11][12]. ...
Recently, the use of emulsion as a delivery system for essential oils has attracted increasing attention. In this research, cinnamon essential oil Pickering emulsion (ZCCPEs) stabilized by zein-pectin composite nanoparticles (ZCPs) was constructed as an effective antimicrobial system. Thereafter, the influence of ZCPs concentration on the stability of ZCCPEs was studied. The results showed that 0.25% ZCPs could reduce the bioorganic matter by four times compared with 1% ZCPs while maintaining good physical stability. The inhibitory effect of ZCCPEs on two food-related microorganisms (i.e. Alternaria alternata and Botrytis cinerea) was evaluated by antimicrobial assay. In addition, two fresh-cut apple slices models were constructed to systematically evaluate the application potential of ZCCPEs in food preservation. Due to the well dispersibility and sustained-release ability, ZCCPEs showed superior antibacterial performance than pure essential oil. The fabricated zein-pectin based Pickering emulsions might provide a promising alternative for the delivery of antimicrobial essential oils in the food industries.
Alzheimer's disease (AD), one of the most common neurodegenerative diseases, is a major factor contributing to cognitive impairment in older adults. Current therapeutic treatments can only relieve the symptoms of AD, but they cannot stop the progression of the disease because it takes a long time for clinical symptoms to manifest. Therefore, it is essential to develop effective diagnostic strategies for early detection and treatment of AD. As the most common genetic risk factor for AD, apolipoprotein E4 (ApoE4) is present in more than half of patients with AD, and it can be a target protein for AD therapy. We used molecular docking, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations to investigate the specific interactions between ApoE4 and Cinnamon-derived compounds. Of the 10 compounds, epicatechin was found to have the highest binding affinity to ApoE4 because the hydroxyl groups of epicatechin form strong hydrogen bonds with the Asp130 and Asp12 residues of ApoE4. Therefore, we proposed some epicatechin derivatives by adding a hydroxyl group to epicatechin and studied their interactions with ApoE4. The FMO results indicate that the addition of a hydroxyl group to epicatechin increases its binding affinity to ApoE4. It is also revealed that the Asp130 and Asp12 residues of ApoE4 are important for the binding between ApoE4 and the epicatechin derivatives. These findings will help propose potent inhibitors against ApoE4, leading to a proposal for effective therapeutic candidates for AD.
Objectives
Regarding neurocognitive and immunomodulatory properties of cinnamon (Cinn) we aimed to investigate whether cinnamon regulates acetylcholinesterase (AChE) activity, and oxidative abnormalities with concomitant memory dysfunction in streptozotocin (STZ)-induced diabetes.
Methods
47 male adult rats were divided into seven groups (n=8 animals): Control group: in these non-diabetic rats only saline 0.9% NaCl was gavaged, Diabetic (Dia) group: diabetic rats in them saline 0.9% NaCl was gavaged for six weeks. Dia-Cinn 100, Dia-Cinn 200, and Dia-Cinn 400, Dia-Met groups: in these diabetic rats the extract (100, 200, 400 mg/kg respectively) or metformin (300 mg/kg) was gavaged for six weeks. Passive avoidance performance, AChE enzyme activity, and oxidative indicators were examined among the groups.
Results
vs. the Control group, blood glucose level and stay time in the dark were remarkably increased in Dia group whereas the latency time was decreased. Meanwhile, antioxidant levels (superoxide dismutase, catalase, and thiols) noticeably decreased in the Dia group compared to the Control group. On the other hand, Cinn extract espicailly at the highest dose recovered the changes similar to those found in the metformin-treated group.
Conclusions
These findings proposed that the cinnamon hydro-ethanolic extract promotes memory recovery in diabetic conditions through the atteuation of the AChE activity and oxidative injury.
Herbs, Spices and Their Roles in Nutraceuticals and Functional Foods gives an overview of the many pharmacological activities associated with herbs and spices, including detailed coverage on their mechanisms and formulations for the food industry. Chapters focus on key ingredients such as Curcuma longa, Piper Nigrum and Trigonella foenum-graecum, with contributors across the globe providing the latest research and advances for each. This is an essential read for scientists who want to understand the fundamental mechanisms behind the bioactive compounds within herbs and spices. The numerous phytochemicals present in plant extracts have multiple pharmacological activities so there is extensive research into new bioactive compounds. The pharmacological activities of herbs and spices have been thoroughly investigated, and it is crucial that the latest research is organized into a comprehensive resource.
Abstract
Neurological disorders are the foremost occurring diseases across the globe resulting in progressive dysfunction, loss of neuronal structure ultimately cell death. Therefore, attention has been drawn toward the natural resources for the search of neuroprotective agents. Plant-based food bioactives have emerged as potential neuroprotective agents for the treatment of neurodegenerative disorders. This comprehensive review primarily focuses on various plant food bioactive, mechanisms, therapeutic targets, in vitro and in vivo studies in the treatment of neurological disorders to explore whether they are boon or bane for neurological disorders. In addition, the clinical perspective of plant food bioactives in neurological disorders are also highlighted. Scientific evidences point toward the enormous therapeutic efficacy of plant food bioactives in the prevention or treatment of neurological disorders. Nevertheless, identification of food bioactive components accountable for the neuroprotective effects, mechanism, clinical trials, and consolidation of information flow are warranted. Plant food bioactives primarily act by mediating through various pathways including oxidative stress, neuroinflammation, apoptosis, excitotoxicity, specific proteins, mitochondrial dysfunction, and reversing neurodegeneration and can be used for the prevention and therapy of neurodegenerative disorders. In conclusion, the plant based food bioactives are boon for neurological disorders.
Keywords:
Bioactives
neurodegeneration
targets
mechanism
preclinical
The current scientific community is facing a daunting challenge to unravel reliable natural compounds with realistic potential to treat neurological disorders such as Alzheimer’s disease (AD). The reported compounds/drugs mostly synthetic deemed the reliability and therapeutic potential largely due to their complexity and off-target issues. The natural products from nutraceutical compounds emerge as viable preventive therapeutics to fill the huge gap in treating neurological disorders. Considering that Alzheimer’s disease is a multifactorial disease, natural compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs so far used to treat Alzheimer’s disease. A wide range of plant extracts and phytochemicals reported to possess the therapeutic potential to Alzheimer’s disease includes curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and other phytochemicals such as huperzine A, limonoids, and azaphilones. Reported targets of these natural compounds include inhibition of acetylcholinesterase, amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc. We tenaciously aimed to review the in-depth potential of natural products and their therapeutic applications against Alzheimer’s disease, with a special focus on a diversity of medicinal plants and phytocompounds and their mechanism of action against Alzheimer’s disease pathologies. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against Alzheimer’s disease with lesser side effects as compared to currently available treatments.
A large number of plasma proteomic biomarkers have been discovered in the field of neurodegenerative diseases. Novel biomarker molecules in plasma and serum could significantly reduce the need for invasive methods in clinical practice such as the lumbar puncture for CSF collection and may be useful to specific patients. Furthermore, candidate biomarker proteins that have been identified and validated could be used to discriminate Αlzheimer's disease patients from MCI and healthy controls in clinical trials, before the onset of clinical symptoms as well as to improve personalized therapies. The development of new blood-based biomarkers via proteomic technology offers a deep knowledge in the pathophysiology of neurodegenerative diseases and involves in the development of new therapeutic targets. This report presents numerous dietary compounds that either promote or suppress the expression of biomarkers mainly in the blood of AD or MCI subjects.
Alzheimer's disease (AD) is the most prevalent dementia in the elderly, causing disability, physical, psychological, social, and economic damage to the individual, their families, and care- givers. Studies have shown some spices, such as saffron, rosemary, cinnamon, turmeric, and ginger, have antioxidant and anti-inflammatory properties that act in inhibiting the aggregation of acetylcholinesterase and amyloid in AD. For this reason, spices have been studied as beneficial sources against neurodegenerative diseases, including AD. In this sense, this study aims to present a review of some spices (Saffron, Rosemary, Cinnamon, Turmeric and Ginger) and their bioactive compounds, most consumed and investigated in the world regarding AD. In this article, scientific evidence is compiled in clinical trials in adults, the elderly, animals, and in vitro, on properties considered neuroprotective, having no or negative effects on neuroprotection of these spices and their bioactive compounds. The importance of this issue is based on the pharmacological treatment for AD that is still not very effective. In addition, the recommendations and prescriptions of these spices are still permeated by questioning and lack of robust evidence of their effects on neurodegeneration. The literature search suggests all spices included in this article have bioactive compounds with anti-inflammatory and antioxidant actions associated with neuroprotection. To date, the amounts of spice ingestion in humans are not uniform, and there is no consensus on its indication and chronic consumption guarantees safety and efficacy in neuroprotection. Therefore, clinical evidence on this topic is necessary to become a formal adjuvant treatment for AD.
Negative psychological and physiological consequences of neurodegenerative disorders represent a high social and health cost. Among the neurodegenerative disorders Alzheimer's disease (AD) is recognized as a leading neurodegenerative condition and a primary cause of dementia in the elderlys. AD is considered as neurodegenerative disorder that progressively impairs cognitive function and memory. According to current epidemiological data, about 50 million people worldwide are suffering from AD. The primary symptoms of AD are almost inappreciable and usually comprise forgetfulness of recent events. Numerous processes are involved in the development of AD, for example oxidative stress (OS) mainly due to mitochondrial dysfunction, intracellular the accumulation of hyperphosphorylated tau (τ) proteins in the form of neurofibrillary tangles, excessive the accumulation of extracellular plaques of beta-amyloid (Aβ), genetic and environmental factors. Running treatments only attenuate symptoms and temporarily reduce the rate of cognitive progression associated with AD. This means that most treatments focus only on controlling symptoms, particularly in the initial stages of the disease. In the past, the first choice of treatment was based on natural ingredients. In this sense, diverse natural products (NPs) are capable to decrease the symptoms and alleviate the development of several diseases including AD attracting the attention of the scientific community and the pharmaceutical industry. Specifically, numerous NPs including flavonoids, gingerols, tannins, anthocyanins, triterpenes and alkaloids have been shown anti-inflammatory, antioxidant, anti-amyloidogenic, and anti-cholinesterase properties. This review provide a summary of the pathogenesis and the therapeutic goals of AD. It also discusses the available data on various plants and isolated natural compounds used to prevent and diminish the symptoms of AD.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder with obscure etiology and no disease‐modifying therapy to date. Hence, novel, safe, and low cost‐effective approaches employing medicinal plants are currently receiving increased attention. A growing body of evidence has revealed that cinnamon, being widely used as a spice of unique flavor and aroma, may exert neuroprotective effects in several neurodegenerative diseases, including PD. In vitro evidence has indicated that the essential oils of Cinnamomum species, mainly cinnamaldehyde and sodium benzoate, may protect against oxidative stress‐induced cell death, reactive oxygen species generation, and autophagy dysregulation, thus acting in a potentially neuroprotective manner. In vivo evidence has demonstrated that oral administration of cinnamon powder and sodium benzoate may protect against dopaminergic cell death, striatal neurotransmitter dysregulation, and motor deficits in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse models of PD. The underlying mechanisms of its action include autophagy regulation, antioxidant effects, upregulation of Parkin, DJ‐1, glial cell line‐derived neurotrophic factor, as well as modulation of the Toll‐like receptors/nuclear factor‐κB pathway and inhibition of the excessive proinflammatory responses. In addition, in vitro and in vivo studies have shown that cinnamon extracts may affect the oligomerization process and aggregation of α‐synuclein. Herein, we discuss recent evidence on the novel therapeutic opportunities of this phytochemical against PD, indicating additional mechanistic aspects that should be explored and potential obstacles/limitations that need to be overcome for its inclusion in experimental PD therapeutics.
Mounting evidence suggests a link between metabolic syndrome in the progression of neurodegenerative diseases, where mitochondrial defects and altered balance of reactive oxygen species play a crucial role in such disease progression. Though there have been many clinical trials exploring the efficacy of using cinnamon and its metabolites in the treatment of metabolic syndrome and neurodegenerative diseases, their results are mostly inconclusive; thus, it is important to effectively design clinical trials where the effect would be monitored with validated biomarker- and clinical marker-based surrogate end points. Even though clinical trials with cinnamon as a therapy has been carried out, very few clinical trials or animal studies have been performed with Cinnamomum zeylanicum. This chapter provides a comparative analysis of cinnamon clinical trials in healthy people versus patients with metabolic syndrome and neurological disorders in order to determine the effect of cinnamon on metabolic syndrome and neurological diseases.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder with obscure etiology and no disease‐modifying therapy to date. Hence, novel, safe, and low cost‐effective approaches employing medicinal plants are currently receiving increased attention. A growing body of evidence has revealed that cinnamon, being widely used as a spice of unique flavor and aroma, may exert neuroprotective effects in several neurodegenerative diseases, including PD. In vitro evidence has indicated that the essential oils of Cinnamomum species, mainly cinnamaldehyde and sodium benzoate may protect against oxidative stress‐induced cell death, reactive oxygen species generation, and autophagy dysregulation, thus acting in a potentially neuroprotective manner. In vivo evidence has demonstrated that oral administration of cinnamon powder and sodium benzoate may protect against dopaminergic cell death, striatal neurotransmitter dysregulation, and motor deficits in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse models of PD. The underlying mechanisms of its action include autophagy regulation, antioxidant effects, upregulation of Parkin, DJ‐1, glial cell line‐derived neurotrophic factor, as well as modulation of the TLR/NF‐κB pathway and inhibition of the excessive proinflammatory responses. In addition, in vitro and in vivo studies have shown that cinnamon extracts may affect the oligomerization process and aggregation of α‐synuclein. Herein, we discuss recent evidence on the novel therapeutic opportunities of this phytochemical against PD, indicating additional mechanistic aspects that should be explored, and potential obstacles/limitations that need to be overcome, for its inclusion in experimental PD therapeutics.
Objective
To assess the efficacy of herbal medicine (cinnamon/fennel/ginger) for treating primary dysmenorrhea.
Methods
Relevant studies were searched in multiple databases. The weighted mean difference (WMD) was used as the effect indicator for measurement data, and each effect size was given estimates and 95% confidence intervals (CIs).
Results
Nine studies with 647 patients were selected. Compared with the results in the control group, pain intensity was significantly relieved in the trial group when assessed by the intervention (cinnamon vs. placebo: WMD = 1.815, 95% CI = 1.330–2.301; fennel vs. placebo: WMD = 0.528, 95% CI = 0.119–6.829; ginger vs. placebo: WMD = 2.902, 95% CI = 2.039–3.765), observation period (one cycle: WMD = 2.061, 95% CI = 0.815–3.307; one cycles: WMD = 1.831, 95% CI = 0.973–2.690), and study quality (high quality: WMD = 2.224, 95% CI = 1.488–2.960). Pain duration was significantly shorter in the trial group (cinnamon vs. placebo: WMD = 16.200, 95% CI = 15.271–17.129). No publication bias was observed for either outcome.
Conclusions
For primary dysmenorrhea, cinnamon/fennel/ginger effectively reduced pain intensity, and cinnamon shortened the duration of pain. Further studies are needed to confirm our results.
Background: Few studies have been done considering the effectiveness of aqueous extract of cinnamon in neurological diseases. In previous studies, reducing the pain of hydro-alcoholic cinnamon extract in the second phase (chronic) of the formalin test and reduction of inflammation in animal models as well as in humans following cinnamon administration have been emphasized. There are also studies on the anti-Alzheimerchr('39')s effects of this extract. However, the effects of CWE of this plant on the incidence of diseases associated with the nervous system, especially depression, have not been investigated.
Objective: In the present study, the effects of CWE on depression induced by forced swimming test (FST) in mice were investigated.
Methods: Cinnamon aqueous extract was obtained by boiling method of cinnamon powder. Male NMRI mice (25-30 g) were used (n=8/group). Different doses of CWE (25, 50, 100, and 200 mg/kg) were administered intraperitoneally to the animals 30 min before the (FST). In addition, fluoxetine (20 mg/kg) was administered to distinct animals as positive control.
Results: Intraperitoneal (50, 100, and 200 mg/kg) injections of CWE significantly reduced the animals’ immobilization in a dose-dependent manner which in doses of 100 and 200 mg/kg was similar to fluoxetine effect.
Conclusion: It could be concluded that the CWE can inhibit depression induced by FST in mice. Since the exact composition of the extract is not identified, the exact mechanism(s) by which the extract reduces the FST is not clear.
Protein misfolding diseases (PMDs) are chronic and progressive, with no effective therapy so far. Aggregation and misfolding of amyloidogenic proteins are closely associated with the onset and progression of PMDs, such as amyloid-β in Alzheimer's disease, α-Synuclein (α-Syn) in Parkinson's disease and human islet amyloid polypeptide (hIAPP) in type 2 diabetes. Inhibiting toxic aggregation of amyloidogenic proteins is regarded as a promising therapeutic approach in PMDs. The past decade has witnessed the rapid progresses of this field, dozens of inhibitors have been screened and verified in vitro and in vivo, demonstrating inhibitory effects against the aggregation and misfolding of amyloidogenic proteins, together with beneficial effects. Natural products are major sources of small molecule amyloid inhibitors, a number of natural derived compounds have been identified with great bioactivities and translational prospects. Here, we review the non-polyphenolic natural inhibitors that potentially applicable for PMDs treatment, along with their working mechanisms. Future directions are proposed for the development and clinical applications of these inhibitors.
Objectives: Cholinergic system dysfunction was found to play a key role in Alzheimer's disease (AD) pathogenesis. Therefore, the animal model of scopolamine-induced amnesia has been widely used in AD researches. Cinnamon, as a spice commonly used in cuisine, has been shown to exert some therapeutic effects. The most abundant compound in cinnamon is cinnamaldehyde which recently was shown to exert several neuroprotective effects in animal models. Therefore, this study aimed to assess whether cinnamaldehyde has the potency to prevent memory retrieval impairment and hippocampal protein kinase B (Akt) and MAPK (extracellular signal-regulated kinase (ERK)) alterations induced by scopolamine in mice.
Methods: Adult male mice were pretreated with cinnamaldehyde (12.5, 25, 40 and 100 mg/kg/oral gavage) 10 days before training. The training of passive avoidance task was performed on the 10th day and a memory retention test was done 24 h later. Scopolamine (1 mg/kg) was injected intraperitoneally, 30 min before the retention test to induce memory retrieval deficit. At the complement of the behavioral experiments, the hippocampi were isolated for western blot analysis to assess the phosphorylated and total levels of hippocampal MAPK and Akt proteins.
Results: The results showed that cinnamaldehyde pretreatment at the dose of 100 mg/kg significantly prevented the amnesic effect of scopolamine. Furthermore, cinnamaldehyde prevented scopolamine induced dysregulations of hippocampal MAPK and Akt.
Discussion: The results of the present study revealed that oral sub-chronic cinnamaldehyde administration has the capability to prevent memory retrieval deficit induced by cholinergic blockade and restores hippocampal MAPK and Akt dysregulations.
Alzheimer"s disease (AD) is a devastative neurodegenerative disorder with complex etiology. AD is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuro-inflammation, hypo-metabolism; it decreases in acetylcholine levels and a reduction of cerebral blood flow. It is also not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides but hyper phosphorylated Tau (tubulin binding protein) which formed senile plaque and intracellular neurofibrillary tangles respectively. However, despite the long-term and worldwide effort for a more effective therapy, the only available treatment is a symptomatic use of acetylcholinesterase inhibitors and memantine. Then, many researchers focused their attention to modulate amyloid-beta peptides. These therapeutic approaches as well as those based on cholinergic or amyloid theory have not brought the desired benefits yet. Thus, the main features related with the Tau pathology found in AD are Tau phosphorylation and aggregation. Based on the biochemically diverse range of pathological Tau protein, a number of approaches have been proposed to develop new potential therapeutics like inhibition of Tau phosphorylation, proteolysis and aggregation; promotion of intra-and extracellular Tau clearance and stabilization of microtubules (MTs). Medicinal plants have been used in different systems of medicine and exhibited their powerful roles in the management and cure of memory disorders. This review paper discusses the potential of medicinal plant molecules to targeting Tau protein in Alzheimer"s disease therapy.
Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary conditions as well as cardiovascular, gastrointestinal and bone disease. Although data on abnormalities of DNA methylation and their role in the development of diseases are abundant, less is known about the impact of histone modifications and microRNA expressions. Further, we discussed the effects of selected common environmental toxicants on epigenetic modifications and their association with particular abnormalities. A number of different environmental toxicants have been identified for their role in aberrant DNA methylation, histone modifications, and microRNA expression. Such epigenetic effects were shown to be tissue-type specific and highly associated with the level and duration of exposure. Finally, we described present and future therapeutic strategies, including medicines and dietary compounds for combating the toxicant-induced epigenetic alterations. There are currently seven histone deacetylase inhibitors and two DNA methyltransferase inhibitors approved for clinical use and many other promising candidates are in preclinical and clinical testing. Dietary compounds are thought to be the effective and safe strategies for treating and prevention of epigenetic pathophysiological conditions. Still more concentrated epigenetic researches are required for evaluation of chemical toxicity and identifying the causal association between key epigenetic alteration and disease.
Ethnopharmacological relevance:
Cinnamomum verum (CV), also known as 'Dalchini', is the dry bark of the Cinnamomum verum (L.) plant, and has been used as a traditional Pakistani medicine to alleviate pain and inflammation in patients suffering from arthritic rheumatism. It contains alkaloids, triterpenes, Cinnamaldehyde and other volatile oils. The aim of the present study was to investigate the underlying biological effect of ethyl alcohol (EtOH) and methyl alcohol (MeOH) extracts from CV on collagen type-II induced arthritic (CIA) mice.
Materials and methods:
Gas chromatography mass spectrophotometry was used to perform fingerprinting identification of the EtOH and MeOH extracts. CIA mice model was established by subdermal injections of type-II bovine collagen (CII) on the 1st, 8th and 14th day of the experiment. Ethyl alcohol extract and methyl alcohol extract (1 mg/KgBW, 2 mg/KgBW and 4 mg/KgBW), was orally administered from the 15th day onwards for 2 weeks. Progression of oedema and joint inflammation was measured in the paws using a digital Vernier calliper every 3 days from day 1 till the end of the experiment. The oxidative scavenging ability of cinnamaldehyde was evaluated using a DPPH assay. Similarly, the nitrogen free radical (NOS) production of isolated lymphocytes was evaluated using Greiss's method. The spleen index was calculated and knee joint changes were observed by histopathological sectioning. Western blot analysis was performed on peripheral blood derived serum for CII, CAPN1, TNFα and NFATc3.
Results:
Extracts were shown to be enriched in trans-cinnamaldehyde and its analogues. Extracts showed good ameliorative effects (p < 0.05) after day 2 of treatment. A greater therapeutic role was observed for the 4 mg/kgBW dosage of the methanolic extract (p < 0.01). Swelling in the spleen was greatly reduced along with the generation of free radicals by lymphocytes, post treatment. There was also an inhibitory role by the extracts on NFATc3 (p < 0.05), TNF-Alpha (p < 0.05), CAII (p < 0.05) and mCalpain (p < 0.05) all proteins involved in RA.
Conclusion:
In this study, it has been demonstrated that administration of CV has a therapeutic potential on CIA. The data suggest that CV could have a potential role in the treatment of RA patients.
The burden of chronic disease is greater in individuals with dementia, a patient group that is growing as the population is aging. The cornerstone of optimal management of chronic disease requires effective patient self-management. However, this is particularly challenging in older persons with a comorbid diagnosis of dementia. The impact of dementia on a person’s ability to self-manage his/her chronic disease (eg, diabetes mellitus or heart failure) varies according to the cognitive domain(s) affected, severity of impairment and complexity of self-care tasks. A framework is presented that describes how impairment in cognitive domains (attention and information processing, language, visuospatial ability and praxis, learning and memory and executive function) impacts on the five key processes of chronic disease self-management. Recognizing the presence of dementia in a patient with chronic disease may lead to better outcomes. Patients with dementia require individually tailored strategies that accommodate and adjust to the individual and the cognitive domains that are impaired, to optimize their capacity for self-management. Management strategies for clinicians to counter poor self-management due to differentially impaired cognitive domains are also detailed in the presented framework. Clinicians should work in collaboration with patients and care givers to assess a patient’s current capabilities, identify potential barriers to successful self-management and make efforts to adjust the provision of information according to the patient’s skill set. The increasing prevalence of age-related chronic illness along with a decline in the availability of informal caregivers calls for innovative programs to support self-management at a primary care level.
Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed.
This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in converting poor learning mice to good learning ones. NaB, but not sodium formate, was found to upregulate plasticity-related molecules, stimulate NMDA- and AMPA-sensitive calcium influx and increase of spine density in cultured hippocampal neurons. NaB induced the activation of CREB in hippocampal neurons via protein kinase A (PKA), which was responsible for the upregulation of plasticity-related molecules. Finally, spatial memory consolidation-induced activation of CREB and expression of different plasticity-related molecules were less in the hippocampus of poor learning mice as compared to good learning ones. However, oral treatment of cinnamon and NaB increased spatial memory consolidation-induced activation of CREB and expression of plasticity-related molecules in the hippocampus of poor-learning mice and converted poor learners into good learners. These results describe a novel property of cinnamon in switching poor learners to good learners via stimulating hippocampal plasticity.
Vanillic acid (VA) found in vanilla and cinnamic acid (CA) the precursor of flavonoids and found
in cinnamon oil, are natural plant phenolic acids which are secondary aromatic plant products
suggested to possess many physiological and pharmacological functions. In vitro and in vivo
experiments have shown that phenolic acids exhibit powerful effects on biological responses
by scavenging free radicals and eliciting antioxidant capacity. In the present study, we
investigated the antioxidant capacity of VA and CA by the trolox equivalent antioxidant
capacity (TEAC) assay, cytotoxicity by neutral red uptake (NRU) assay in Chinese Hamster Ovary
(CHO) cells and also the genotoxic and antigenotoxic effects of these phenolic acids using the
cytokinesis-blocked micronucleus (CBMN) and the alkaline comet assays in human peripheral
blood lymphocytes. At all tested concentrations, VA (0.17–67.2 mg/ml) showed antioxidant
activity but CA (0.15–59.2 mg/ml) did not show antioxidant activity against 2,2-azino-bis
(3-ethylbenz-thiazoline-6-sulphonic acid) (ABTS). VA (0.84, 4.2, 8.4, 16.8, 84 and 168 mg/ml) and
CA (0.74, 3.7, 7.4, 14.8, 74, 148 mg/ml) did not have cytotoxic and genotoxic effects alone at the
studied concentrations as compared with the controls. Both VA and CA seem to decrease DNA
damage induced by H2O2 in human lymphocytes.
Trans-cinnamaldehyde (TCA), an essential oil in cinnamon powder, may have beneficial effects as a treatment for stroke which is the second leading cause of death worldwide. Post-ischemic inflammation induces neuronal cell damage after stroke, and activation of microglia, in particular, has been thought as the main contributor of proinflammatory and neurotoxic factors. The purpose of this study was to investigate the neuroprotective effects of TCA in an animal model of ischemia/reperfusion (I/R)-induced brain injury and the neuroprotective mechanism was verified in LPS-induced inflammation of BV-2 microglial cells. Our results showed that TCA (10-30 mg/kg, p.o.) significantly reduced the infarction area, neurological deficit score and decreased iNOS and COX-2 protein expression level in I/R-induced injury brain tissue. It inhibited 0.5 µg/ml LPS-induced NO production in BV-2 microglial cells without affecting cell viability, reduced protein expression of iNOS and COX-2, and attenuated inhibition of p53 protein. TCA also suppressed the effects of LPS-induced nuclear translocation of NF-κB p65 and p50 and increased cytosolic IκBα. It also reduced LPS-induced mRNA expression of iNOS, COX-2, and TNFα. We concluded that TCA has a potential neuroprotective effect to against the ischemic stroke, which may be via the inhibition of neuroinflammation through attenuating iNOS, COX-2 expression and NF-κB signaling pathway.
We investigated the anti-amnesic effects of SJ and fermented SJ (FSJ) on scopolamine (SCO)-induced amnesia mouse model. Mice were orally co-treated with SJ or FSJ (125, 250, and 500 mg/kg) and SCO (1 mg/kg), which was injected intraperitoneally for 14 days. SCO decreased the step-through latency and prolonged latency time to find the hidden platform in the passive avoidance test and Morris water maze test, respectively, and both SCO effects were ameliorated by FSJ treatment. FSJ was discovered to promote hippocampal neurogenesis during SCO treatment by increasing proliferation and survival of BrdU-positive cells, immature/mature neurons. In the hippocampus of SCO, oxidative stress and the activity of acetylcholinesterase were elevated, whereas the levels of acetylcholine and choline acetyltransferase were diminished; however, all of these alterations were attenuated by FSJ-treatment. The alterations in brain-derived neurotrophic factor, phosphorylated cAMP response element-binding protein, and phosphorylated Akt that occurred following SCO treatment were protected by FSJ administration. Therefore, our findings are the first to suggest that FSJ may be a promising therapeutic drug for the treatment of amnesia and aging-related or neurodegenerative disease-related memory impairment. Furthermore, the molecular mechanism by which FSJ exerts its effects may involve modulation of the cholinergic system and BDNF/CREB/Akt pathway.
Herbal medicines with high amounts of phytochemicals have been shown to have beneficial effects on blood pressure (BP), endothelial function and anthropometric measures. This study aimed to determine the effect of herbal treatment on BP, endothelial function and anthropometric measures in patients with type 2 diabetes mellitus (T2DM). This clinical trial included 204 T2DM patients randomly assigned to four intervention groups receiving 3 g cinnamon, 3 g cardamom, 1 g saffron or 3 g ginger with three glasses of black tea, and one control group consuming only three glasses of tea without any herbals, for 8 weeks. Intercellular adhesion molecule-1 (ICAM-1), systolic and diastolic BP and anthropometric measures were collected at baseline and after 8 weeks. No significant difference was found between various medicinal plants in terms of influencing BP, serum soluble (s)ICAM-1 concentrations and anthropometric measures. However, in within-group comparison saffron and ginger intakes significantly reduced sICAM-1 concentrations (340.9 ± 14.4 vs 339.69 ± 14.4 ng/ml, p = 0.01, and 391.78 ± 16.0 vs 390.97 ± 15.8 ng/ml, p = 0.009, respectively) and ginger intake affected systolic BP (143.06 ± 0.2 vs 142.07 ± 0.2 mmHg, p = 0.02). Although administration of these herbal medicines as supplementary remedies could affect BP and sICAM-1 concentrations, there was no significant difference between the plants in terms of influencing anthropometric measures, BP and endothelial function.
For some classes of dietary polyphenols, there are now sufficient intervention studies to indicate the type and magnitude of effects among humans in vivo, on the basis of short-term changes in biomarkers. Isoflavones (genistein and daidzein, found in soy) have significant effects on bone health among postmenopausal women, together with some weak hormonal effects. Monomeric catechins (found at especially high concentrations in tea) have effects on plasma antioxidant biomarkers and energy metabolism. Procyanidins (oligomeric catechins found at high concentrations in red wine, grapes, cocoa, cranberries, apples, and some supplements such as Pycnogenol) have pronounced effects on the vascular system, including but not limited to plasma antioxidant activity. Quercetin (the main representative of the flavonol class, found at high concentrations in onions, apples, red wine, broccoli, tea, and Ginkgo biloba) influences some carcinogenesis markers and has small effects on plasma antioxidant biomarkers in vivo, although some studies failed to find this effect. Compared with the effects of polyphenols in vitro, the effects in vivo, although significant, are more limited. The reasons for this are 1) lack of validated in vivo biomarkers, especially in the area of carcinogenesis; 2) lack of long-term studies; and 3) lack of understanding or consideration of bioavailability in the in vitro studies, which are subsequently used for the design of in vivo experiments. It is time to rethink the design of in vitro and in vivo studies, so that these issues are carefully considered. The length of human intervention studies should be increased, to more closely reflect the long-term dietary consumption of polyphenols.
Endocrine disrupting chemicals (EDC) are released into environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDC have major risks for human by targeting different organs and systems in the body. Multiple mechanisms are involved in targeting the normal system, through estrogen receptors, nuclear receptors and steroidal receptors activation. In this review, different methods by which xenobiotics stimulate signaling pathways and genetic mutation or DNA methylation have been discussed. These methods help to understand the results of xenobiotic action on the endocrine system. Endocrine disturbances in the human body result in breast cancer, ovarian problems, thyroid eruptions, testicular carcinoma, Alzheimer disease, schizophrenia, nerve damage and obesity. EDC characterize a wide class of compounds such as organochlorinated pesticides, industrial wastes, plastics and plasticizers, fuels and numerous other elements that exist in the environment or are in high use during daily life. The interactions and mechanism of toxicity in relation to human general health problems, especially endocrine disturbances with particular reference to reproductive problems, diabetes, and breast, testicular and ovarian cancers should be deeply investigated. There should also be a focus on public awareness of these EDC's risks and their use in routine life. Therefore, the aim of this review is to summarize all evidence regarding different physiological disruptions in the body and possible involved mechanisms, to prove the association between endocrine disruptions and human diseases.
The most prevalent metabolic disorders are diabetes mellitus, obesity, dyslipidemia, osteoporosis and metabolic syndrome, which are developed when normal metabolic processes are disturbed. The most common pathophysiologies of the above disorders are oxidative stress, Nrf2 pathways, epigenetic, and change in miRNA expression. There is a challenge in the prevention and treatment of metabolic disorders due to severe adverse effects of some synthetic drugs, their high cost, lack of safety and poverty in some conditions, and insufficient accessibility for the general population in the world. With increasing interest in shifting from synthetic drugs to phytotherapy as an alternative treatment, there is still a gap in scientific evidences of plant-derived therapeutic benefits. One reason may be slow rate of translation of animal studies' findings into human clinical trials. Since metabolic disorders are multifactorial, it seems that poly-herbal medications, or drug-herbal combination are needed for their treatment. However, further researches to determine the most effective plant-derived metabolites, and their cellular mechanism in order to set priorities for well-designed animal and clinical trials, and also more studies with strong scientific evidences such as systematic review and meta-analysis of controlled studies are needed.
Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.
Dietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing.
Mean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers.
This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.
Alzheimer's disease (AD) is a neurodegenerative disorder that impacts the daily lives of many sufferers through memory loss as well as behavioral and cognitive changes. AD is the most common form of dementia. One in ten people over the age of 65, and around half of those over 85 have AD. AD can be divided into familial (early-onset) and sporadic (late-onset) cases, with the familial form (<1%) linked to mutations in three major genes (amyloid precursor protein, presenilin-1 and 2), and the sporadic form (>99% of cases) caused by a variety of genetic (e.g., apolipoprotein E), metabolic and environmental factors. The AD brain is characterized macroscopically by cortical atrophy, caused by degeneration of the cholinergic axonal arborisation and shrinkage of the dendritic tree. Microscopically, amyloid beta peptide deposits (senile plaques) and neurofibrillary tangles are present in affected areas (Gil-Bea et al., 2012). AD is also characterized by chronic neuroinflammation, driven by activation of astroglia and microglia (Rosenblum, 2014). In addition, levels of pro-inflammatory mediators or cytokines which include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors are elevated in the brains of patients with AD (Latta et al., 2014). Furthermore, nuclear translocation of NF-κB and STAT-1α, transcription factors involved in pro-inflammatory gene expression, indicates the presence of a sustained pro-inflammatory process (Lawrence, 2009). Drug Discovery Difficulties Faced in Alzheimer's Disease Drug discovery for AD has been strongly focused on β-amyloid (initially plaques, then soluble oligomers), as genetic evidence from the familial cases supported by the hypothesis that β-amyloid must be driving the disease process. Based on the " amyloid cascade hypothesis, " anti-amyloid therapies were hoped to deliver a cure for AD (Robinson et al., 2004). Unfortunately, numerous clinical trials with active and passive amyloid vaccines as well as G-secretase inhibitors have failed (reviewed in Castello et al., 2014). Currently, there are no disease-modifying drugs available for AD. Consequently, alternative therapeutic targets, such as neuroinflammation have been suggested for the prevention and treatment of AD (Shi et al., 2013; Latta et al., 2014). As the expression of many pro-inflammatory cytokines is driven by the transcription factor NF-κB (Hoffmann et al., 2006), we propose that brain-permeable inhibitors of NF-κB signaling have the potential to prevent or slow down the progression of AD.
It is well documented that hyperglycemia-induced oxidative stress is an important causative factor of endothelial dysfunction. Cinnamaldehyde (CA) is a key flavor compound in cinnamon essential oil that can enhance the antioxidant defense against reactive oxygen species (ROS) by activating NF-E2-related factor 2 (Nrf2), which has been shown to have a cardiovascular protective effect, but its role in endothelial dysfunction induced by high glucose is unknown.
Dissected male C57BL/6J mouse aortic rings and HUVECs were cultured in normal glucose(NG 5.5 mM) or high glucose(HG 30.0 mM) DMEM treatment with or without CA (10 µM).
Treatment with CA protected the endothelium relaxation, inhibited ROS generation and preserved nitric oxide (NO) levels in the endothelium of mouse aortas treated with high glucose . CA up-regulated Nrf2 expression, promoted its translocation to the nucleus'and increased HO-1, NQO1, Catalase and Gpx1 expression under high glucose condition. The increased level of nitrotyrosine in HUVECs under high glucose was also attenuated by treatment with CA. Dihydroethidium (DHE) and DAF-2DA staining indicated that CA inhibited the ROS generation and preserved the NO levels in HUVECs, but these effects were reversed by Nrf2-siRNA in high glucose conditions.
Our results indicated that CA protected endothelial dysfunction under high glucose conditions and this effect was mediated by Nrf2 activation and the up-regulation of downstream target proteins. CA administration may represent a promising intervention in diabetic patients who are at risk for vascular complications. © 2015 S. Karger AG, Basel.
Cinnamon stick is world widely used in cooking, traditional medicine, perfumery and aesthetic industries. Many studies have demonstrated the potential of cinnamon extracts in diabetes treatment. Although it has been reported as safe in general cooking recipe and categorized as GRAS by USDA, sub-acute toxicity procedure was conducted in this study to determine effect of cinnamon extract on histopathological changes as well as the haematological parameters of blood. Water extraction was done for dried cinnamon. Twenty-four female Sprague Dawley rats were used in this study. The oral route was selected because it is the most likely route of human exposure through the consumption of herbs. The concentrations studied were 0.1, 0.5 and 2.0g/kg cinnamon aqueous extract (CE). There were no statistically significant effects of all concentrations of CE on behaviour, mortality, water intake, food consumption, weight gain, internal organs weight (liver and kidney) and heamatological parameters during treatment and post-treatment periods except 1) the slight decrease in kidney and liver weight of rats treated with 0.5g/kg and 2) slight decrease in liver weight of rats treated with 2.0g/kg, during post-treatment period. Hence, these toxicity studies suggest that the CE is low to moderate in toxicity and CE below 0.5 g/kg dose level is safe to be used in the efficacy study especially for diabetes treatment.
The death of retinal ganglion cells is a hallmark of many optic neurodegenerative diseases such as glaucoma and retinopathy. Oxidative stress is one of the major reasons to cause the cell death. Oligomeric proanthocyanidin has many health beneficial effects including antioxidative and neuroprotective actions. Here we tested whether oligomeric proanthocyanidin may protect retinal ganglion cells against oxidative stress induced-apoptosis in vitro. Retinal ganglion cells were treated with hydrogen peroxide with or without oligomeric proanthocyanidin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that treating retinal ganglion cell line RGC-5 cells with 20 μmol/L oligomeric proanthocyanidin significantly decreased the hydrogen peroxide (H2O2) induced death. Results of flow cytometry and Hoechst staining demonstrated that the death of RGC-5 cells was mainly caused by cell apoptosis. We further found that expression of pro-apoptotic Bax and caspase-3 were significantly decreased while anti-apoptotic Bcl-2 was greatly increased in H2O2 damaged RGC-5 cells with oligomeric proanthocyanidin by western blot assay. Furthermore, in retinal explant culture, the number of surviving retinal ganglion cells in H2O2-damaged retinal ganglion cells with oligomeric proanthocyanidin was significantly increased. Our studies thus demonstrate that oligomeric proanthocyanidin can protect oxidative stress-injured retinal ganglion cells by inhibiting apoptotic process.
This study investigated the fumigant toxicity of oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components against the Japanese termite (Reticulitermes speratus). The fumigant toxicity of oriental sweetgum and valerian oil differed significantly according to exposure time. Oriental sweetgum showed toxicity at short exposure times (2 days), and the toxicity of valerian oil was high 7 days after treatment. The main constituents of oriental sweetgum and valerian oils were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, benzyl alcohol, acetophenone, 1-phenyl-1-ethanol, hydrocinnamyl alcohol, trans-cinnamyl aldehyde, trans-cinnamyl alcohol, cis-asarone, styrene, and cis-ocimene showed toxicity against Japanese termites 7 days after treatment. Hydrocinnamyl alcohol and trans-cinnamyl alcohol were found to be the major contributors to the fumigant antitermitic toxicity of oriental sweetgum oil. The acetylcholinesterase (AChE) inhibition activity of two oils and their constituents was tested to determine their mode of action. Only cis-ocimene showed strong AChE inhibition activity with an IC50 value of 0.131 mg/mL. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control.
Alzheimer's disease (AD) is a neurodegenerative disorder mainly characterized by amyloid-β (Aβplaques, neurofibrillary tangles, loss of synapses and neurons and chronic neuroinflammation. Emerging data highlight the involvement of innate immunity, that has been shown to play opposing roles during the AD progression. Activated microglia and reactive astrocytes exert neuroprotection mediated through Aβphagocytosis in the early stage, whereas, as the disease progresses, they fail in Aβclearance and exert detrimental effects, including neuroinflammation and neurodegeneration. Specific toll-like receptors (TLRs) and coreceptors can be directly or indirectly activated to induce Aβ uptake or inflammatory responses, depending on the disease stage. Fibrillar Aβcan directly interact with TLR2, TLR4, and CD14 to induce microglial Aβphagocytosis in the beginning stages, and neuroinflammatory responses in the late stages. Early TLR3-mediated signal enhances neuronal Aβautophagy, although it increases neuronal apoptosis in the late AD stage. Similarly, TLR7, TLR8 and TLR9 can enhance microglial Aβuptake in the early stage, but over time they contribute to neuroinflammation. Therefore, TLRs, and in particular TLR2 and TLR4, represent a suitable target for therapeutic intervention within the disease progression and targeting them carefully could increase Aβautophagy and phagocytosis or reduce inflammatory responses. Several modulators with selective TLR agonist or antagonist activity have been developed, and many of them could have a therapeutic benefit in AD patients. This paper outlines the role of specific TLRs in AD, also focusing on TLR-targeted compounds yet indicated for the treatment of other inflammatory diseases, that could be used to treat the different stages of the disease.
Cinnamon (Cinnamomum zeylanicum, and Cinnamon cassia), the eternal tree of tropical medicine, belongs to the Lauraceae family. Cinnamon is one of the most important spices used daily by people all over the world. Cinnamon primarily contains vital oils and other derivatives, such as cinnamaldehyde, cinnamic acid, and cinnamate. In addition to being an antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, lipid-lowering, and cardiovascular-disease-lowering compound, cinnamon has also been reported to have activities against neurological disorders, such as Parkinson's and Alzheimer's diseases. This review illustrates the pharmacological prospective of cinnamon and its use in daily life.
A simple and efficient flow injection mass spectrometric (FIMS) method was developed to differentiate cinnamon (Cinnamomum) bark (CB) samples of the four major species (C. burmannii, C. verum, C. aromaticum, and C. loureiroi) of cinnamon. Fifty cinnamon samples collected from China, Vietnam, Indonesia, and Sri Lanka were studied using the developed FIMS fingerprinting method. The FIMS fingerprints of the cinnamon samples were analyzed using principal component analysis (PCA). The FIMS technique required only 1 min of analysis time per sample. The representative samples from each of the four major species of cinnamon were further examined using an ultrahigh-performance liquid chromatography-high-resolution mass spectrometry system, and the chemical differences between the four species were profiled. The results showed that the 1 min FIMS fingerprinting method successfully differentiated the four cinnamon species studied.
Insulin resistance leads to memory impairment. Cinnamon (CN) improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr) diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App) were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.
