PMID: 

Front Microbiol. 2019 ;10:2241. Epub 2019 Sep 25. PMID: 31608045

Abstract Title: 

Antimicrobial Activity of Cinnamaldehyde onBiofilms.

Abstract: 

is considered the most relevant bacteria in the transition of non-pathogenic commensal oral microbiota to biofilms which contribute to the dental caries process. The present study aimed to evaluate the antimicrobial activity of a natural plant product, cinnamaldehyde againstbiofilms. Minimum inhibitory concentrations (MIC), minimal bactericidal concentration (MBC), and growth curves were determined to assess its antimicrobial effect against planktonic. The biofilm biomass and metabolism with different concentrations of cinnamaldehyde and different incubation time points were assessed using the crystal violet and MTT assays. The biofilms were visualized using confocal laser scanning microscopy (CLSM). Bacterial cell surface hydrophobicity, aggregation, acid production, and acid tolerance were evaluated after cinnamaldehyde treatment. The gene expression of virulence-related factors (,,,,,,,and) was investigated by real-time PCR. The MIC and MBC of cinnamaldehyde against planktonicwere 1000 and 2000μg/mL, respectively. The results showed that cinnamaldehyde can decrease biofilm biomass and metabolism at sub-MIC concentrations. CLSM images revealed that the biofilm-covered surface areas decreased with increasing concentrations of cinnamaldehyde. Cinnamaldehyde increased cell surface hydrophobicity, reducedaggregation, inhibited acid production, and acid tolerance. Genes expressions in the biofilms were down-regulated in the presence of cinnamaldehyde. Therefore, our data demonstrated that cinnamaldehyde at sub-MIC level suppressed the microbial activity onbiofilm by modulating hydrophobicity, aggregation, acid production, acid tolerance, and virulence gene expression.

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PMID: 

Appl Microbiol Biotechnol. 2019 Nov ;103(21-22):9037-9055. Epub 2019 Oct 28. PMID: 31659418

Abstract Title: 

Cinnamaldehyde inhibits Candida albicans growth by causing apoptosis and its treatment on vulvovaginal candidiasis and oropharyngeal candidiasis.

Abstract: 

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed thatC. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discoveredthat when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid-Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.

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PMID: 

Fitoterapia. 2019 Nov ;139:104405. Epub 2019 Nov 7. PMID: 31707126

Abstract Title: 

A review of cinnamaldehyde and its derivatives as antibacterial agents.

Abstract: 

There is a continuing rise in the occurrence of multidrug-resistant bacterial infections. Antibiotic resistance to currently available antibiotics has become a global health issue leading to an urgent need for alternative antibacterial strategies. There has been a renewed interest in the development of antibacterial agents from natural sources, and trans-cinnamaldehyde is an example of a naturally occurring compound that has received significant attention in recent years. Trans-Cinnamaldehyde has been shown to possess substantial antimicrobial activity, as well as an array of other medicinal properties, and represents an intriguing hit compound from which a number of derivatives have been developed. In some cases, these derivatives have been shown to possess improved activity, not only compared to trans-cinnamaldehyde but also to commonly used antibiotics. Therefore, understanding the antibacterial mechanisms of action that these compounds elicit is imperative in order to facilitate their development and the development of new antibacterial agents that could exploit similar mechanistic approaches. The purpose of this review is to provide an overview of current knowledge on the antibacterial activity and mechanisms of action of cinnamaldehyde and its derivatives, and to highlight significant contributions made in this research area. It is hoped that the findings presented in this work will aid the future development of new antibacterial agents.

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PMID: 

Microb Pathog. 2020 Mar ;140:103946. Epub 2019 Dec 23. PMID: 31874231

Abstract Title: 

Inhibitory effects of Cinnamaldehyde, Carvacrol, and honey on the expression of exoS and ampC genes in multidrug-resistant Pseudomonas aeruginosa isolated from burn wound infections.

Abstract: 

This study aimed to evaluate the effects of Cinnamaldehyde, Carvacrol, and honey either alone or in combinations on the expression of exoS and ampC genes in multidrug-resistant (MDR) P. aeruginosa isolates. Thirty-five P. aeruginosa isolates were recovered from burn wound infections of patients admitted to the burn ward of Besat hospital of Hamadan, Iran, during 2018. Antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method to identify MDR isolates. The antibacterial effects of Cinnamaldehyde, Carvacrol, and honey either alone or in combinations with each other were compared to Imipenem (as the control group) using the broth dilution method. The expressions of exoS and ampC genes were determined in bacteria treated with sub-minimum inhibitory concentration (MIC) of the ternary combination of Cinnamaldehyde, Carvacrol, and honey by Real-Time-PCR. The data were analyzed using SPSS software applying student t-test, Kruskal-Wallis, and Mann-Whitney U tests. The P-value less than 0.05 was considered as statistically significant. The average MICs of Cinnamaldehyde, Carvacrol, and honey were 0.82-0.01, 0.01-0.6, and 62.5-250 μg/mL, respectively. The average MIC of the mentioned compounds was 430 times lower than that of Imipenem. A synergistic effect was detected between these drugs against 70% of the isolates. At sub-MIC concentration, the triple combination of Cinnamaldehyde, Carvacrol, and honey reduced the expressions of exoS and ampC genes by 6.12 and 2.85 folds, respectively. The combination of Cinnamaldehyde, Carvacrol, and honey showed a higher antibacterial effect than Imipenem. However, it needs confirmation with more isolates.

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PMID: 

Cancers (Basel). 2020 Jan 29 ;12(2). Epub 2020 Jan 29. PMID: 32013122

Abstract Title: 

Cinnamaldehyde Enhances Antimelanoma Activity through Covalently Binding ENO1 and Exhibits a Promoting Effect with Dacarbazine.

Abstract: 

At present, melanoma is a common malignant tumor with the highest mortality rate of all types of skin cancer. Although the first option for treating melanoma is with chemicals, the effects are unsatisfactory and include poor medication response and high resistance. Therefore, developing new medicines or a novel combination approach would be a significant breakthrough. Here, we present cinnamaldehyde (CA) as a potential candidate, which exerted an antitumor effect in melanoma cell lines. Chemical biology methods of target fishing, molecular imaging, and live cell tracing by an alkynyl-CA probe revealed that theα-enolase (ENO1) protein was the target of CA. The covalent binding of CA with ENO1 changed the stability of the ENO1 protein and affected the glycolytic activity. Furthermore, our results demonstrated that dacarbazine (DTIC) showed a high promoting effect with CA for antimelanoma both in vivo andin vitro. The combination improved the DTIC cell cycle arrest in the S phase and markedly impacted melanoma growth. As a covalent inhibitor of ENO1, CA combined with DTIC may be beneficial in patients with drug resistance in antimelanoma therapy.

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PMID: 

J Pharmacol Exp Ther. 2020 Feb 6. Epub 2020 Feb 6. PMID: 32029577

Abstract Title: 

Cinnamaldehyde inhibits inflammation of human synoviocyte cells through regulation of Jak/Stat pathway and ameliorates collagen-induced arthritis in rats.

Abstract: 

Cinnamaldehyde (Cin), a bioactive cinnamon essential oil from traditional Chinese medicine (TCM) herb Cinnamomum cassia, has been reported to have multi-pharmacological activities including anti-inflammation. However, its role and molecular mechanism of anti-inflammatory activity in musculoskeletal tissues remains unclear. Here, we first investigated the effects and molecular mechanisms of Cin in human synoviocyte cells. Then in vivo therapeutic effect of Cin on collagen-induced arthritis (CIA) also studied. Cell cytotoxicity was measured by CCK-8 Assay. Pro-inflammatory cytokine expression was evaluated using qPCR and ELISA. Protein expression was measured by western blotting. The in vivo effect of Cin (75 mg/kg/day) was evaluated in rats with CIA by gavage administration. Disease progression was assessed by clinical scoring, radiographic, and histological examinations. Cin significantly inhibited IL-1β-induced interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) release from human synoviocyte cells. The molecular analysis revealed that Cin impaired IL-6-induced janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1) and STAT3 signaling pathway by inhibiting the phosphorylation of JAK2, STAT1 and STAT3, without affecting NF-κB pathway. Cin reduced collagen-induced swollen paw volume of arthritic rats. The anti-inflammation effects of Cin were associated with decreased severity of arthritis, joint swelling, and reduced bone erosion anddestruction. Furthermore, serum IL-6 level was decreased when Cin administered therapeutically to CIA rats. Cin suppresses IL-1β-induced inflammation in synoviocytes through the JAK/STAT pathway and alleviated collagen-induced arthritis in rats. These data indicated that Cin might be a potential TCM-derived disease modifying anti-rheumatic herbal drug. SIGNIFICANCE STATEMENT: Cin suppresses pro-inflammatory cytokines secretion in RA synoviocyte cells by JAK/STAT pathway. Cin ameliorates collagen-induced arthritis in rats. Cin is a potential TCM-derived disease modifying anti-rheumatic herbaldrug.

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PMID: 

Food Chem. 2020 Feb 12 ;317:126405. Epub 2020 Feb 12. PMID: 32078995

Abstract Title: 

The antifungal effects of cinnamaldehyde against Aspergillus niger and its application in bread preservation.

Abstract: 

Cinnamaldehyde (CIN) is a promising replacement for chemical synthetic preservatives, which has exhibited effective antimicrobial activities in food applications. In this study we examined the antifungal efficiency of CIN against Aspergillus niger in vitro. In addition, we explored its mode of action and evaluated its application potential in bread preservation in situ. The results showed that CIN exerted different levels of antifungal activity through different treatments, wherein it showed the highest antifungal activity in the liquid broth test, followed by solid contact and gas diffusion methods. On the other hand, ultrastructure observation, propyl iodide staining and ergosterol detection showed that CIN may damage the cell ultrastructure and membrane integrity in a dose dependent manner. Besides, the content of reactive oxygen species and malondialdehyde were, respectively, 2.74 and 2.07 times higher in fungi treated with 100 μg/mL of CIN, compared with those in untreated fungi. Finally, shelf life experiment showed that, in the vapor phase, CIN can efficiently prolong the shelf life of bread. Altogether, these results indicate that CIN can be used as an alternative food preservative due to its antifungal effects thatare exerted, at least in part in A. niger, through the induction of oxidative stress, which caused cell damage and increased membrane permeability.

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PMID: 

Neurol Res. 2020 Feb ;42(2):99-107. Epub 2020 Jan 8. PMID: 31910792

Abstract Title: 

Sub-chronic oral cinnamaldehyde treatment prevents scopolamine-induced memory retrieval deficit and hippocampal Akt and MAPK dysregulation in male mice.

Abstract: 

: 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.: 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 10 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.: 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.: 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.

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PMID: 

BMC Complement Med Ther. 2020 Feb 11 ;20(1):45. Epub 2020 Feb 11. PMID: 32046702

Abstract Title: 

In vitro Cariostatic effects of cinnamon water extract on nicotine-induced Streptococcus mutans biofilm.

Abstract: 

BACKGROUND: Dental caries is one of the most prevalent chronic oral diseases worldwide. Dental caries is mainly associated with Streptococcus mutans and the Lactobacillus species. A specific relationship was found between nicotine and S. mutans growth as the presence of nicotine increased S. mutans biofilm formation. Nicotine is able to increase the number of S. mutans and extracellular polysaccharide (EPS) synthesis. Among the widely used herbs and spices is cinnamon which demonstrated a strong antibacterial activity against a wide variety of bacteria including S. mutans and showed the ability to inhibit S. mutans biofilm formation. Cinnamon essential oil, obtained from the leaves of C. zeylanicum, has been demonstrated to be effective against S. mutans and Lactobacillus acidophilus, which are partially responsible for dental plaque formation and caries development. The aim of this study was to identify the effects of nicotine exposure on the inhibitory effects of cinnamon water extract on S. mutans biofilm formation.MATERIALS AND METHODS: A 24-h culture of S. mutans UA159 in microtiter plates was treated with varying nicotine concentrations (0-32 mg/ml) in Tryptic Soy broth supplemented with 1% sucrose (TSBS) with or without a standardized concentration (2.5 mg/ml) of cinnamon water extract. A spectrophotometer was used to determine total growth absorbance and planktonic growth. The microtiter plate wells were washed, fixed and stainedwith crystal violet dye and the absorbance measured to determine biofilm formation.RESULTS: The presence of 2.5 mg/ml cinnamon water extract inhibits nicotine-induced S. mutans biofilm formation from 34 to 98% at different concentrations of nicotine (0-32 mg/ml).CONCLUSION: The results demonstrated nicotine-induced S. mutans biofilm formation is decreased from 34 to 98% in the presence of 2.5 mg/ml cinnamon water extract. This provides further evidence about the biofilm inhibitory properties of cinnamon water extract and reconfirms the harmful effects of nicotine.

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PMID: 

Diabetes Metab Syndr. 2020 Jan 30 ;14(2):119-125. Epub 2020 Jan 30. PMID: 32032898

Abstract Title: 

Effect of cinnamon supplementation on blood pressure and anthropometric parameters in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials.

Abstract: 

BACKGROUND AND AIMS: The present systematic review and meta-analysis was conducted to investigate the effect of cinnamon supplementation on blood pressure and anthropometric indices in patients with type 2 diabetes.METHODS: PubMed, Embase, Scopus, Web of Science and Cochrane Library were systematically searched to find relevant records up to 22 August 2019. Standard mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the effect of cinnamon supplementation on the outcomes of this study. In the case of heterogeneity, fixed and random effect models were used. The obtained data were analyzed by Stata 13. After excluding irrelevant records, 9 eligible articles were included.RESULTS: This meta-analysis found a significant reduction in systolic blood pressure (SBP) (SMD: -0.532, 95% CI: [-1.032, -0.033], P = 0.037) and diastolic blood pressure (DBP) (SMD: -0.681, 95% CI: [-1.297, -0.065], P = 0.030) of patients with type 2 diabetes following cinnamon supplementation. Based on the results of the present study, cinnamon supplementation had no significant effect on the body weight (BW) (SMD: -0.309, 95% CI: [-0.793, 0.175], P = 0.211), body mass index (BMI) (SMD: -0.550, 95% CI: [-1.244, 0.144], P = 0.120). and waist circumference (WC) (SMD: -0.235, 95% CI: [-0.518, 0.047], P = 0.103).CONCLUSIONS: Cinnamon supplementation significantly decreased SBP and DBP of patients with type 2 diabetes. Although cinnamon intake caused changes in anthropometric parameters, the observed changes were not statistically significant.

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