OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

Acrolein, known as one of the most common reactive carbonyl species, is a toxic small molecule affecting human health in daily life. This study is focused on the scavenging abilities and mechanism of ferulic acid and some other phenolic acids against acrolein. Among the 13 phenolic compounds investigated, ferulic acid was found to have the highest efficiency in scavenging acrolein under physiological conditions. Ferulic acid remained at (3.04±1.89)% and acrolein remained at (29.51±4.44)% after being incubated with each other for 24 h. The molecular mechanism of the detoxifying process was also studied. Detoxifying products, namely 2-methoxy-4-vinylphenol (product 21) and 5-(4-hydroxy-3-methoxyphenyl)pent-4-enal (product 22), were identified though nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS), after the scavenging process. Ferulic acid showed significant activity in scavenging acrolein under physiological conditions. This study indicates a new method for inhibiting damage from acrolein.
Acrolein/toxicity* ; Coumaric Acids/pharmacology* ; Glutathione/physiology* ; Hydroxybenzoates/pharmacology* ; Magnetic Resonance Spectroscopy ; Structure-Activity Relationship

OBJECTIVETo examine the mechanism underlying the beneficial role of cinnamaldehyde on oxidative damage and apoptosis in high glucose (HG)-induced dorsal root ganglion (DRG) neurons in vitro.

METHODSHG-treated DRG neurons were developed as an in vitro model of diabetic neuropathy. The neurons were randomly divided into five groups: the control group, the HG group and the HG groups treated with 25, 50 and 100 nmol/L cinnamaldehyde, respectively. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis rate was evaluated by the in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. The intracellular level of reactive oxygen species (ROS) was measured with flow cytometry. Expression of nuclear factor-kappa B (NF-κB), inhibitor of κB (IκB), phosphorylated IκB (p-IκB), tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and caspase-3 were determined by western blotting and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were also measured by western blotting.

RESULTSCinnamaldehyde reduced HG-induced loss of viability, apoptosis and intracellular generation of ROS in the DRG neurons via inhibiting NF-κB activity. The western blot assay results showed that the HG-induced elevated expressions of NF-κB, IκB and p-IκB were remarkably reduced by cinnamaldehyde treatment in a dose-dependent manner (P <0.01). The HG-induced over-expression of NF-κB p65 mRNA was remarkably attenuated after cinnamaldehyde treatment in a dose-dependent manner (P <0.01). However, the expressions of Nrf2 and HO-1 were not upregulated. Treatment with cinnamaldehyde not only attenuated caspase-3 activation and the caspase cleavage cascade in DRG neurons, but also lowered the elevated IL-6, TNF-α, cyclo-oxygenase and inducible nitric oxide synthase levels, indicating a reduction in inflammatory damage.

CONCLUSIONSCinnamaldehyde protected DRG neurons from the deleterious effects of HG through inactivation of NF-κB pathway but not through activation of Nrf2/HO-1. And thus cinnamaldehyde may have potential application as a treatment for DPN.

Acrolein ; administration & dosage ; analogs & derivatives ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Ganglia, Spinal ; drug effects ; metabolism ; pathology ; Glucose ; toxicity ; Heme Oxygenase (Decyclizing) ; metabolism ; I-kappa B Proteins ; metabolism ; Interleukin-6 ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; NF-kappa B ; metabolism ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; Oxidation-Reduction ; drug effects ; Phosphorylation ; drug effects ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Trans-cinnamaldehyde, the main component of volatile oil from cassia twig or Cinnamomum cassia, which is a traditional Chinese herbal medicine. Trans-cinnamaldehyde is a kind olefine aldehyde of organic compounds and has many pharmacological properties, such as anti-inflammatory, anti-tumor, anti-bacterial, antidiabetic, anti-obesity, and neuroprotection etc. The compound has preventive and therapeutic effects on the nervous system, cardiovascular, cancer, diabetes and other diseases. Trans-cinnamaldehyde, as a preventive care of nature medicine, has great clinical and market potential. This paper gives a review about the pharmacological effects and mechanism of trans-cinnamaldehyde researched in the latest five years. We hope to provide some basic information for further research on trans-cinnamaldehyde.
Acrolein ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Cinnamomum aromaticum ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans

OBJECTIVETo explore the inhibitory effect of cinnamaldehyde on invasion capacities of human breast cancer cell line MDA-MB-435S and its relation with regulating the expression of miR-27a.

METHODSThe effect of cinnamaldehyde on invasive capacities of MDA-MB-435S was measured by Transwell matrigel invasion assay. The effect of miR-27a expression on invasive capabilities of MDA-MB-435S, the intervention of cinnamaldehyde in the miR-27a expression, and its relation with its effect on invasive capabilities were defected with liposome 2000 transinfection miRNA27a mimics/inhibitors, real time-polymerase chain reaction (Real-time PCR), and Transwell chamber model.

RESULTSCompared with the control group, the number of cells passing through the transwell chamber was more significantly reduced after treated by cinnamaldehyde for 12 h (P < 0.05). The miR-27a expression was 962.07 times and 40% of that of the control group after transinfected by miR-27a mimics and miR-27a inhibitors. After transinfected by miR-27a inhibitors, the number of cells passing through the transwell chamber was more significantly reduced (P < 0.05). The miR-27a expression of MDA-MB-435S was down-regulated by 12-h treatment of cinnamaldehyde (2(-deltaCt) = 0.56, 0.18, 0.18, respectively). The number of miR-27a mimics transinfection pretreated MDA-MB-435S cells passing through the transwell chamber increased more obviously than the number of un-pretreated MDA-MB-435S cells in the control group (P < 0.05).

CONCLUSIONSCinnamaldehyde could inhibit invasive capabilities of human breast cancer cell line MDA-MB-435S. The over-expression of miR-27a played an important role in the invasive capability of MDA-MB-435S. The inhibition of cinnamaldehyde on invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a.

Acrolein ; analogs & derivatives ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; MicroRNAs ; genetics

OBJECTIVEThis work was intended to investigate the effect of acrolein fog exposure on the ratio of CD4⁺CD25⁺ regulatory T cells (Treg) and expression of transcription factor Foxp3 in asthmatic rats.

METHODSSixty 6 - 8 weeks male Wistar rats were randomly divided into 4 groups according to random number table (15 rats for each group) which were control group (animals were treated with saline), aerosolized ovalbumin (OVA) exposure group, acrolein exposure group and combined OVA and acrolein fog exposure group, respectively. The rats were exposed to air or/and to saline or OVA aerosol for 6-8 weeks respectively.24 h after the last challenge, 4 ml of peripheral blood and lung tissue were collected from each rat. The percentage of CD4⁺CD25⁺ T cells was determined by flow cytometry analysis. The concentration of interleukin-4 (IL-4) and γ-interferon (IFN-γ) in peripheral blood and lung homogenates were measured by ELISA. The protein expression of Foxp3 in the lung was detected by Western blotting.

RESULTSThe percentage of CD4⁺CD25⁺T cells in aerosolized OVA group ((6.23 ± 1.11)%) was significantly lower than that in the normal saline group ((9.97 ± 1.23)%) (P < 0.01). The percentage of CD4⁺CD25⁺ T cells ((3.26 ± 0.84)%) in OVA combined acrolein fog exposure group was remarkably lower than that in the aerosolized OVA exposure group and in the normal saline group (P < 0.01). IL-4 in both plasma and lung ((22.57 ± 4.34), (0.86 ± 0.12) ng/L) was significantly increased in the OVA exposed rats compared with the normal saline group ((11.57 ± 2.86), (0.31 ± 0.10) ng/L) (P < 0.01). Further remarkable increase in IL-4 of both plasma and lung tissue was observed in the group exposed to both OVA and acrolein ((34.32 ± 6.21), (1.45 ± 0.32)ng/L) compared with the aerosolized OVA exposure group and the normal saline group (P < 0.05). γ-IFN of plasma and lung tissue in OVA exposed group ((59.67 ± 20.12), (0.56 ± 0.17) ng/L) was significantly decreased compared with the normal saline group ((151.74 ± 56.68), (1.54 ± 0.21) ng/L) (P < 0.01), and a further remarkable decrease in IFN-γ of plasma and lung tissue was observed in the group exposed to both OVA and acrolein ((10.12 ± 2.57), (0.49 ± 0.10) ng/L) compared with the aerosolized OVA exposure group and the normal saline group (P < 0.05). Protein expression of Foxp3 in the aerosolized OVA group (8.07 ± 0.24) was lower than that in the normal saline group (10.25 ± 0.31) (P < 0.01), while the protein expression of Foxp3 in OVA combined acrolein fog exposure group (6.38 ± 0.32) was lower than that in the normal saline group and the aerosolized OVA exposure group (P < 0.01).

CONCLUSIONThe number of CD4⁺CD25⁺ Treg cells and the expression of Foxp3 were likely to be altered by acrolein fog exposure, which might play an important role in acrolein induced Th1/Th2 imbalance in asthmatic rats.

Acrolein ; pharmacology ; Animals ; Asthma ; metabolism ; Disease Models, Animal ; Forkhead Transcription Factors ; metabolism ; Male ; Rats ; Rats, Wistar ; T-Lymphocytes, Regulatory ; drug effects ; metabolism

Cinnamaldehyde was shown to have significant anti-inflammatory and anti-pyretic actions in studies from both others' and our lab. Prostaglandin E2 (PGE2) plays a key role in generation of these pathological states, while PGE, synthase-1 (mPGES-1) is one of crucial biological elements in the process of PGE2 production. And as a downstream inducible terminal prostaglandin synthase of COX-2, mPGES-1 is now regarded as a more promising novel drug target than COX-2 and is attracting more and more attention from both academia and pharmaceutical industry. The purpose of present study was to further investigate the anti-inflammatory and antipyretic molecular mechanisms of cinnamaldehyde based on the mouse macrophage cell line RAW264. 7 in vitro. The PGE2 was identified by using the method of enzyme-linked immunosorbent assay (ELISA) and the expression of COX-2 and mPGES-1 at mRNA and protein levels was detected by the Real-time PCR and Western blotting methods respectively. The experimental results suggested that cinnamaldehyde could evidently reverse the increased production of PGE2induced by IL-1beta. Moreover, the up-regulated expression levels of mPGES-1 and COX-2 were significatly decreased. Together, these results provide compelling evidence that the down-regulated actions to both the production of PGE2 as well as the expression of mPGES-I might account for, at least in part, the anti-inflammatory and anti-pyretic effects of cinnamaldehyde.
Acrolein ; analogs & derivatives ; pharmacology ; Animals ; Blotting, Western ; Cell Line ; Dinoprostone ; metabolism ; Interleukin-1beta ; pharmacology ; Intramolecular Oxidoreductases ; metabolism ; Macrophages ; drug effects ; metabolism ; Mice ; Prostaglandin-E Synthases ; Real-Time Polymerase Chain Reaction

The aim of this study was to investigate the apoptosis-inducing effect of cinnamic aldehyde (CA) on chronic myeloid leukemic (CML) cells and its mechanism. K562 cells and primary bone marrow mononuclear cells (MNC) from patients with CML were treated by various concentrations of CA. Flow cytometry was employed to measure the apoptosis of K562 cells and primary CML bone marrow MNC. Western blot was used to determine the expression of C-MYC and the phosphorylation of CrkL in K562 cells, and real-time polymerase chain reaction (real-time PCR) was used to quantify the expression of BCR-ABL mRNA in K562 cells. The results indicated that CA induced the apoptosis of K562 cells in a time- and dose-dependent manner. CA induced apoptosis of CML MNC dose-dependently. CA inhibited the expression of BCR-ABL mRNA and C-MYC, reduced CrkL phosphorylation levels in K562 cells. It is concluded that CA induces apoptosis of CML cells in vitro. Down-regulation of the expression and function of BCR-ABL may be one of its most important anti-leukemia mechanisms.
Acrolein ; analogs & derivatives ; pharmacology ; Apoptosis ; drug effects ; Fusion Proteins, bcr-abl ; metabolism ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; pathology

OBJECTIVETo observe the effects of Cinnamyl aldehyde (CA) on NIH3T3 cell cycle and explore the possible mechanism further.

METHODFlowcytometry was used for observing cell cycle distribution. Expressions of proliferation cell nuclear antigen (PCNA) and Cyclin D1 protein in NIH3T3 cells were assessed by immunocytochemistry.

RESULTAfter culture with CA for 24 hours, the percentage of populations of S phase was enhanced by 3% (P < 0.05) and cell proliferation index (PrI, S + G2/M) was increased by 3.5% (P < 0.01) , but G2/M phase had no obvious changes. The expressions of Cyclin D1 and PCNA proteins were improved markly by CA compared with controlgroup (P < 0.01).

CONCLUSIONCA could promote more cells in G0/G1 phase into S phase, which may be related to the regulation of the expressions of PCNA and Cyclin D1.

Acrolein ; analogs & derivatives ; isolation & purification ; pharmacology ; Animals ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cinnamomum ; chemistry ; Cyclin D1 ; metabolism ; Flow Cytometry ; Immunohistochemistry ; Mice ; NIH 3T3 Cells ; Plants, Medicinal ; chemistry ; Proliferating Cell Nuclear Antigen ; metabolism ; S Phase ; drug effects

To observe the effects of phenylallyl compounds on prostaglandin E2 (PGE2) release in mouse cerebral microvascular endothelial cells (bEnd. 3) stimulated by IL-1beta, and to analyze their structure-activity relationship. Different concentrations of phenylallyl compounds were added separately, and the content of PGE2 induced by IL-1beta in the culture media was measured by ELISA assay. The 50% inhibitory concentration (IC50) of PGE2 was calculated. Studies showed that phenylallyl compounds could affect the PGE2 release differently in bEnd. 3 cells induced by IL-1beta. Close relationships were shown between the inhibitory activities and the location and number of the substituent groups. In conclusion, phenylallyl compounds exhibited inhibitory activities at different extent on PGE2 release in bEnd. 3 cells stimulated by IL-1beta and presented certain structure-activity relationship.
Acrolein ; analogs & derivatives ; isolation & purification ; pharmacology ; Animals ; Brain ; blood supply ; Cells, Cultured ; Cinnamates ; isolation & purification ; pharmacology ; Dinoprostone ; antagonists & inhibitors ; secretion ; Drugs, Chinese Herbal ; chemistry ; Endothelial Cells ; cytology ; metabolism ; Inhibitory Concentration 50 ; Interleukin-1beta ; pharmacology ; Mice ; Microvessels ; cytology ; Propanols ; isolation & purification ; pharmacology ; Structure-Activity Relationship