Comparative characterization of cinnamon, cinnamaldehyde and kaempferol for phytochemical, antioxidant and pharmacological properties using acetaminophen-induced oxidative stress mouse model / Caracterización comparativa de canela, cinamaldehído y kaempferol para propiedades fitoquímicas, antioxidantes y farmacológicas utilizando el modelo de ratón con estrés oxidativo inducido por acetaminofeno

This study was aimed to explore the comparative efficacy of cinnamon bark extract, cinnamaldehyde and kaempferol against acetaminophen (APAP)-induced oxidative stress. Cinnamon bark extract, cinnamaldehyde and kaempferol were utilized or in-vivo analysis. From the results of in-vitro screening tests, cinnamon ethanolic extract was selected for in-vivo study in mouse model. For this, Balb/c albino mice were treated with cinnamon ethanolic extract (200 mg/kg), cinnamaldehyde (10 mg/kg) and kaempferol (10 mg/kg) orally for 14 days followed by single intraperitoneal administration of APAP during 8 hours. Blood and organ samples were collected for biochemical and histopathological analysis. The results showed that cinnamon bark ethanolic extract, cinnamaldehyde and kaempferol ameliorated APAP-induced oxidative stress and organ toxicity in mice. In conclusion, cinnamaldehyde and kaempferol possess comparable antioxidant potential even at 20-times less dose as compared to cinnamon bark ethanolic extract suggesting therapeutic potential in oxidative stress-related disorders.

Este estudio tuvo como objetivo explorar la eficacia comparativa del extracto de corteza de canela, cinamaldehído y kaempferol contra el estrés oxidativo inducido por acetaminofén (APAP). Se utilizaron extracto de corteza de canela, cinamaldehído y kaempferol para el análisis in vivo. De los resultados de las pruebas de detección in vitro, se seleccionó el extracto etanólico de canela para estudio in vivo en modelo de ratón. Para ello, los ratones albinos Balb/c fueron tratados con extracto etanólico de canela (200 mg/kg), cinamaldehído (10 mg/kg) y kaempferol (10 mg/kg) por vía oral durante 14 días, seguido de la administración intraperitoneal única de APAP durante 8 horas. Se recogieron muestras de sangre y órganos para análisis bioquímicos e histopatológicos. Los resultados mostraron que el extracto etanólico de la corteza de canela, el cinamaldehído y el kaempferol mejoraron el estrés oxidativo inducido por APAP y la toxicidad orgánica en ratones. En conclusión, el cinamaldehído y el kaempferol poseen un potencial antioxidante comparable, incluso a una dosis 20 veces menor en comparación con el extracto etanólico de la corteza de canela, lo que sugiere un potencial terapéutico en los trastornos relacionados con el estrés oxidativo.

Alleviation of diabetes-induced hepatotoxicity by date palm hydroalcoholic extract in rat model; a biochemical, immunohistochemical and stereological study / Alivio de la hepatotoxicidad inducida por diabetes mediante el extracto hidroalcohólico de palmera datilera en modelo de rata: un estudio bioquímico, inmunohistoquímico y estereológico

SUMMARY: The present study was aimed to investigate the hepatoprotective effects of date palm hydroalcoholic extract (DP)in diabetic rats using biochemical and histopathological approaches. Diabetes was induced by administration of 60 mg/kg of streptozotocin intraperitoneally. In this analysis 32 adult rats were randomly divided into four groups; group 1: non-diabetic control whic received 0.1 mL normal saline, group 2:served as non-diabetic control which treated with 270 mg/kg of DP, group 3: served as untreated diabetic, and group 4: diabetic rats treated with 270 mg/kg of DP. Diabetic rats treated with the DP extracts exhibited lower hepatic oxidative stress and lower hepatic enzymes level. Extract treatment decreased the level of malondealdehyde (MDA) as a marker of lipid peroxidation. Stereological estimations revealed a significant increase in the liver volume in diabetic rats which was reduced in DP-treated rats. Immunofluorescence staining showed high synthesis of acrolein as a byproduct of lipid proxidation. While, optical density measurement revealed significant decrease in acrolein after DP administration. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and necrotic nuclei, whereas, DP treatment attenuated the adverse effects of diabetes on the liver represented by relatively healthy hepatocytes and sinusoids. The obtained results indicated that date pam extract was beneficial in the prevention of diabetes-induced hepatotoxicity due to its natural antioxidant constituents. Further preclinical and clinical studies are needed for considering this plant in management of prediabetes and diabetes hepatic complications.

RESUMEN: El presente estudio tuvo como objetivo investigar los efectos hepatoprotectores del extracto hidroalcohólico (DP) de la palmera datilera en ratas diabéticas utilizando enfoques bioquímicos e histopatológicos. La diabetes fue inducida mediante la administración de 60 mg / kg de estreptozotocina por vía intraperitoneal. Se dividieron al azar 32 ratas adultas en cuatro grupos; grupo 1: control no diabético que recibió 0,1 mL de solución salina normal, grupo 2: control no diabético tratado con 270 mg / kg de DP, grupo 3: fue separado como diabético no tratado, y grupo 4: ratas diabéticas tratadas con 270 mg / kg de DP mg / kg de DP. Las ratas diabéticas tratadas con los extractos de DP mostraron menor estrés oxidativo hepático y menor nivel de enzimas hepáticas. El tratamiento con extracto disminuyó el nivel de malondealdehído (MDA) como marcador de la proxidación de lípidos. Las estimaciones estereológicas revelaron un aumento significativo en el volumen del hígado en ratas diabéticas que se redujo en las ratas tratadas con DP. La tinción por inmunofluorescencia mostró una alta síntesis de acroleína como subproducto de la proxidación de lípidos. Mientras que, la medición de la densidad óptica reveló una disminución significativa de la acroleína después de la administración de DP. El examen histopatológico mostró cambios significativos en el tejido hepático diabético no tratado manifestados por vena porta dilatada, infiltración leucocítica, degeneración grasa y núcleos necróticos, mientras que el tratamiento con DP atenuó los efectos adversos de la diabetes en el hígado representados por hepatocitos y sinusoides relativamente sanos. Los resultados obtenidos indicaron que el extracto de palmera datilera fue beneficioso en la prevención de la hepatotoxicidad inducida por diabetes debido a sus constituyentes antioxidantes naturales. Se necesitan más estudios clínicos para considerar esta planta en el manejo de la prediabetes y las complicaciones hepáticas de la diabetes.

Therapeutic effect of cinnamaldehyde on ulcerative colitis in mice induced by dextran sulfate sodium with Candida albicans colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway / 中国中药杂志

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of β-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and β-1,3-glucan in serum, reduce the contents of TNF-α, IL-1β, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.

Curcumin Attenuates Acrolein-induced COX-2 Expression and Prostaglandin Production in Human Umbilical Vein Endothelial Cells

OBJECTIVE: Inflammation is crucial to limiting vascular disease. Previously we reported that acrolein, a known toxin in tobacco smoke, might play an important role in the progression of atherosclerosis via an inflammatory response involving cyclooxygenase-2 (COX-2) and prostaglandin production in human umbilical vein endothelial cells (HUVECs). Curcumin has been known to improve vascular function and have anti-inflammatory properties. In this study, we investigated whether curcumin prevents the induction of inflammatory response caused by acrolein.METHODS: Anti-inflammatory effects of curcumin were examined in acrolein-stimulated HUVECs. Induction of proteins, mRNA, prostaglandin and reactive oxygen species (ROS) were measured using immunoblot analysis, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry, respectively.RESULTS: Curcumin attenuates inflammatory response via inhibition of COX-2 expression and prostaglandin production in acrolein-induced human endothelial cells. This inhibition by curcumin results in the abolition of phosphorylation of protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein. Furthermore, curcumin suppresses the production of ROS and endoplasmic reticulum stress via phosphorylation of eukaryotic initiation factor-2α caused by acrolein.CONCLUSION: These results suggest that curcumin might be a useful agent against endothelial dysfunction caused by acrolein-induced inflammatory response.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Direct biodegradation of eugenol to coniferyl aldehyde and other higher value-added products by Gibberella fujikuroi ZH-34

BACKGROUND: Eugenol is an economically favorable substrate for the microbial biotransformation of aromatic compounds. Coniferyl aldehyde is one kind of aromatic compound that is widely used in condiment and medical industries; it is also an important raw material for producing other valuable products such as vanillin and protocatechuic acid. However, in most eugenol biotransformation processes, only a trace amount of coniferyl aldehyde is detected, thus making these processes economically unattractive. As a result, an investigation of new strains with the capability of producing more coniferyl aldehyde from eugenol is required. RESULTS: We screened a novel strain of Gibberella fujikuroi, labeled as ZH-34, which was capable of transforming eugenol to coniferyl aldehyde. The metabolic pathway was analyzed by high-performance liquid chromatography­mass spectrometry and transformation kinetics. The culture medium and biotransformation conditions were optimized. At a 6 h time interval of eugenol fed-batch strategy, 3.76 ± 0.22 g/L coniferyl aldehyde was obtained, with the corresponding yield of 57.3%. CONCLUSIONS: This work improves the yield of coniferyl aldehyde with a biotechnological approach. Moreover, the fed-batch strategy offers possibility for controlling the target product and accumulating different metabolites

Scavenging activity and mechanism study of ferulic acid against reactive carbonyl species acrolein / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

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.

Study of the removal difference in indoor particulate matter and volatile organic compounds through the application of plants

This study was conducted to evaluate the ability of plants to purify indoor air by observing the effective reduction rate among pollutant types of particulate matter (PM) and volatile organic compounds (VOCs). PM and four types of VOCs were measured in a new building that is less than three years old and under three different conditions: before applying the plant, after applying the plant, and a room without a plant. The removal rate of each pollutant type due to the plant was also compared and analyzed. In the case of indoor PM, the removal effect was negligible because of outdoor influence. However, 9% of benzene, 75% of ethylbenzene, 72% of xylene, 75% of styrene, 50% of formaldehyde, 36% of acetaldehyde, 35% of acrolein with acetone, and 85% of toluene were reduced. The purification of indoor air by natural ventilation is meaningless because the ambient PM concentration has recently been high. However, contamination by gaseous materials such as VOCs can effectively be removed through the application of plants.

Study of the removal difference in indoor particulate matter and volatile organic compounds through the application of plants

This study was conducted to evaluate the ability of plants to purify indoor air by observing the effective reduction rate among pollutant types of particulate matter (PM) and volatile organic compounds (VOCs). PM and four types of VOCs were measured in a new building that is less than three years old and under three different conditions: before applying the plant, after applying the plant, and a room without a plant. The removal rate of each pollutant type due to the plant was also compared and analyzed. In the case of indoor PM, the removal effect was negligible because of outdoor influence. However, 9% of benzene, 75% of ethylbenzene, 72% of xylene, 75% of styrene, 50% of formaldehyde, 36% of acetaldehyde, 35% of acrolein with acetone, and 85% of toluene were reduced. The purification of indoor air by natural ventilation is meaningless because the ambient PM concentration has recently been high. However, contamination by gaseous materials such as VOCs can effectively be removed through the application of plants.

Anti-oxidative and anti-inflammatory effects of cinnamaldehyde on protecting high glucose-induced damage in cultured dorsal root ganglion neurons of rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>HG-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.</p><p><b>RESULTS</b>Cinnamaldehyde 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.</p><p><b>CONCLUSIONS</b>Cinnamaldehyde 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.</p>

Research progress of trans-cinnamaldehyde pharmacological effects / 中国中药杂志

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.

Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats.</p><p><b>METHODS</b>Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups.</p><p><b>RESULTS</b>Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all P<0.01. IL-6 was increased in the 2 wk and the 4 wk acrolein exposure group [ (33.28 ± 2.27) ng/L, (46.24 ± 3.16) ng/L] compared with the 2 wk and the 4 wk control group [ (16.37 ± 1.49) ng/L, (17.02 ± 1.43) ng/L] in BALF.Ratio of Th17 was higher in the 2 wk and the 4 wk acrolein exposure groups in peripheral blood (1.82 ± 0.18) %, (3.75 ± 0.48) % and BALF [(7.23 ± 0.27) %, (8.12 ± 0.38) %] compared with the 2 wk [(0.96 ± 0.07) %, (5.64 ± 0.63) %] and the 4 wk control group [(1.01 ± 0.08) %, (5.86 ± 0.57) %]. Ratio of Treg in BALF was higher in the acrolein exposure groups [ (8.83 ± 0.52) %, (12.05 ± 0.74) %] compared with the control groups [(4.37 ± 0.27) %, (5.01 ± 0.37) %]. The level of IL-17 mRNA was increased in the 2 wk and the 4 wk acrolein exposure group in peripheral blood [(25.78 ± 2.31), (34.69 ± 2.01) ] and in BALF [(23.04 ± 1.78), (34.56 ± 3.12)] compared with the 2 wk [(11.04 ± 2.53), (11.08 ± 2.05)] and the 4 wk [(12.03 ± 2.34), (12.69 ± 2.69)] control groups. Foxp3 mRNA was increased in the acrolein exposure groups [ (26.37 ± 3.24), (33.19 ± 2.98)] (24.4 ± 2.7), (30.3 ± 2.7) compared with the control groups [(12.37 ± 2.56), (13.12 ± 3.08)]. Th17 in acrolein exposure groups was positively correlated with counts of total cells and macrophages (r=0.5126, 0.5437, all P<0.01).</p><p><b>CONCLUSIONS</b>A changed expression of Th17 and Treg cells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats.</p>

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 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>Compared 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).</p><p><b>CONCLUSIONS</b>Cinnamaldehyde 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.</p>

Polyamines and Their Metabolites as Diagnostic Markers of Human Diseases

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

A Case of Occupational Asthma in a Plastic Injection Process Worker

OBJECTIVES: We report a case of death due to asthma attack in a plastic injection process worker with a history of asthma. METHODS: To assess task relevance, personal history including occupational history and medical records were reviewed. Samples of the substances utilized in the injection process were collected by visiting the patient's workplace. The work environment with the actual process was reproduced in the laboratory, and the released substances were evaluated. RESULTS: The medical records confirmed that the patient's conventional asthma was in remission. The analysis of the resins discharged from the injection process simulation revealed styrene, which causes occupational asthma, and benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, and octadecyl ester. Even though it was not the case in the present study, various harmful substances capable of inducing asthma such as formaldehyde, acrolein, and acetic acid are released during resin processing. CONCLUSION: A worker was likely to occur occupational asthma as a result of the exposure to the harmful substances generated during the plastic injection process.

Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

Fibrinogen is a key protein involved in coagulation and its deposition on blood vessel walls plays an important role in the pathology of atherosclerosis. Although the causes of fibrinogen (fibrin) deposition have been studied in depth, little is known about the relationship between fibrinogen deposition and reactive carbonyl compounds (RCCs), compounds which are produced and released into the blood and react with plasma protein especially under conditions of oxidative stress and inflammation. Here, we investigated the effect of glycolaldehyde on the activity and deposition of fibrinogen compared with the common RCCs acrolein, methylglyoxal, glyoxal and malondialdehyde. At the same concentration (1 mmol/L), glycolaldehyde and acrolein had a stronger suppressive effect on fibrinogen activation than the other three RCCs. Fibrinogen aggregated when it was respectively incubated with glycolaldehyde and the other RCCs, as demonstrated by SDS-PAGE, electron microscopy and intrinsic fluorescence intensity measurements. Staining with Congo Red showed that glycolaldehyde- and acrolein-fibrinogen distinctly formed amyloid-like aggregations. Furthermore, the five RCCs, particularly glycolaldehyde and acrolein, delayed human plasma coagulation. Only glycolaldehyde showed a markedly suppressive effect on fibrinogenesis, none did the other four RCCs when their physiological blood concentrations were employyed, respectively. Taken together, it is glycolaldehyde that suppresses fibrinogenesis and induces protein aggregation most effectively, suggesting a putative pathological process for fibrinogen (fibrin) deposition in the blood.

Effect of acrolein exposure on the percentage of CD4⁺CD25⁺ regulatory T cells and expression of transcription factor Foxp3 in asthmatic rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>This 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.</p><p><b>METHODS</b>Sixty 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>The 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.</p>

Cinnamaldehyde decreases interleukin-1beta induced PGE2 production by down-regulation of mPGES-1 and COX-2 expression in mouse macrophage RAW264.7 cells / 中国中药杂志

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.

Mechanism of cinnamic aldehyde-inducing apoptosis of chronic myeloid leukemic cells in vitro / 中国实验血液学杂志

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.