Novas estratégias terapêuticas para o controle de biofilmes orais: terapia fotodinâmica e sistema carreador de antimicrobianos / New therapeutic strategics for the control of oral biofilms: photodynamic therapy and drug delivery system

Os biofilmes orais possuem grande relevância clínica por estarem associados com o desenvolvimento de cárie dentária e candidose bucal, que são doenças infecciosas frequentemente encontradas na população. O presente trabalho foi dividido em dois estudos: Estudo 1 que teve como objetivo analisar os efeitos da terapia fotodinâmica antimicrobiana (TFDa), mediada por Fotoenticine (FTC) e Azul de Metileno (AM), sobre biofilmes microcosmos de cárie dentária; e Estudo 2 cujo objetivo foi avaliar o gellan gum como biomaterial para carreador do antifúngico Ester fenetil do ácido caféico (CAPE) contra Candida albicans. No estudo 1, amostras de dentina cariada foram coletadas de diferentes pacientes para formar biofilmes microcosmos in vitro. Os biofilmes foram tratados com FTC ou AM associado à irradiação LED a 660 nm (28,5 J/cm²). Os dados foram analisados pela contagem de Unidades Formadoras de Colônias (UFC/mL). Além disso, a biomassa, estrutura do biofilme e produção de ácidos pelos microrganismos foram determinadas por análises microscópicas ou espectrofotométricas. Os biofilmes de diferentes pacientes apresentaram variações na composição microbiana, sendo formados por estreptococos, lactobacilos e leveduras. No geral, a TFDa diminuiu 3,7 Log10 do total de microrganismos, 2,8 Log10 de estreptococos, 3,2 Log10 de lactobacilos e 3,2 Log10 de leveduras, e atingiu a erradicação de estreptococos do grupo mutans. A TFDa também foi capaz de reduzir a biomassa, desagregar os biofilmes e diminuir a concentração de ácidos em 1,1 a 1,9 mmol de lactato/L. Em relação ao estudo 2, inicialmente, foram preparadas formulações do CAPE em diferentes concentrações de gellan gum (0,6 a 1%). As formulações foram avaliadas em relação ao sistema de liberação e ação antifúngica contra C. albicans. Verificou-se que concentrações mais altas de gellan (0,9 e 1%) levaram a uma liberação mais prolongada do CAPE em relação as concentrações mais baixas. Os valores de concentração inibitória mínima do CAPE sobre C. albicans foram aumentados quando esse composto foi incorporado no gellan. As formulações de CAPE em gellan apresentaram atividade antifúngica tanto em culturas planctônicas como em biofilmes de C. albicans, sendo esses efeitos dependentes do tempo de tratamento. O CAPE e suas formulações em gellan também levaram a uma diminuição da atividade proteolítica de C. albicans. Concluiu-se que a TFDa mediada por Fotoenticine e o sistema carreador de gellan gum podem ser estratégias terapêuticas promissoras para o controle dos biofilmes na cavidade bucal, podendo ser usadas respectivamente no tratamento da cárie e candidose. (AU)

Dental caries and oral candidiasis are infectious diseases frequently found in the population. The present work is divided into two studies, study 1 time as objective: To analyze the effects of antimicrobial photodynamic therapy (aPDT), mediated by Fotoenticine (FTC) and Methylene Blue (MB), on dental caries microcosm biofilms. In study 2, the objective was to evaluate gellan gum as a biomaterial to carry the antifungal caffeic acid phenethyl ester (CAPE) on Candida albicans. To conduct study 1, carious dentin samples were collected from different patients to form in vitro microcosm biofilms. The biofilms were treated with FTC or MB associated with 660 nm red LED irradiation, with energy dose of 28.5 J/cm² and power dose of 40 mW/cm². The data were analyzed by the count of Colony Forming Units (CFU/mL). In addition, the biomass, biofilm structure and acid production of the microorganisms were determined by microscopic or spectrophotometric analysis. The biofilms from different patients showed variations in microbial composition, being formed by streptococci, lactobacilli, and yeasts. Overall, aPDT decreased 3.7 Log10 of total microorganisms, 2.8 Log10 of streptococci, 3.2 Log10 of lactobacilli and 3.2 Log10 of yeasts, and achieved eradication of mutans group streptococci. PDTa was also able to reduce biomass, disaggregate biofilms, and decrease acid concentration by 1.1 to 1.9 mmol lactate/L. For study 2 of this, first the standards of CAPE were determined, such as minimum inhibitory concentration, and absorption peak, then CAPE was incorporated into gellan gum, and then the standard curve test and analysis of CAPE release was performed, finally the formulations were tested on planktonic culture and biofilm of different strains of C. albicans, it was also analyzed the action of this drug on the production of Sap. The MIC found varied from 32 to 64 µg/mL, the release tests showed a gradual release in the higher formulations, finally in the CFU/mL count both in planktonic culture and biofilm the formulations were able to inhibit the fungus. With this it is concluded that both aPDT for oral microcosm and gellan gum as caregiver of CAPE for Candida albicans inhibition are promising. (AU)

The ameliorative effects of caffeic acid phenethyl ester in cisplatin-induced nephrotoxicity: assessment of the oxidative stress an inflammation / Los efectos de mejora del éster fenetílico del ácido cafeico en la nefrotoxicidad inducida por cisplatino: evaluación del estrés oxidativo y la inflamación

SUMMARY: The aim of this study is to determine the potential therapeutic effects of CAPE in CP-induced nephrotoxicity in rats. Cisplatin (CP) is an antineoplastic chemotherapeutic used for treatment of many cancer types but its applications may induce nephrotoxicity. Caffeic acid phenethyl ester (CAPE) is an active component of propolis and it has several important physiological activities. Rats were divided into four groups: Control, CAPE (10 µmol/kg/i.p), CP (7 mg/kg/i.p), and CP+CAPE (7 mg/kg/i.p, CP and 10 µmol/kg/i.p, CAPE). After administrations, animals were sacrificed, and kidney tissues were extracted. Histopathological changes were evaluated and TNF-α and IL-6 immunostaining were performed. Moreover, tissue SOD, CAT and MDA levels were measured by ELISA assay to assessment of oxidative stress and lipid peroxidation. CP group showed histopathological deterioration compared to the Control group and CAPE treatment attenuated this damage. When compared with Control and CAPE group, an increase in TNF-α and IL-6 immunoreactivities and tissue MDA levels were observed in the CP group while a decrease in tissue SOD and CAT levels were detected. Furthermore, an improvement was observed in the CP+CAPE compared to the CP group. We suggest that CAPE can be used as a therapeutic agent to attenuate the toxic effects of cisplatin, thanks to its antioxidant and anti-inflammatory properties.

RESUMEN: El objetivo de este estudio fue determinar los posibles efectos terapéuticos de éster fenetílico del ácido cafeico (EFAC) en la nefrotoxicidad inducida por cisplatino (CP) en ratas. El CP es un quimioterapéutico antineoplásico utilizado para el tratamiento de muchos tipos de cáncer, sin embargo sus aplicaciones pueden inducir nefrotoxicidad. El EFAC es un componente activo del propóleo y tiene varias actividades fisiológicas importantes. Para el estudio las ratas se dividieron en cuatro grupos: Control, EFAC (10 µmol / kg / ip), CP (7 mg / kg / ip) y CP + EFAC (7 mg / kg / ip, CP y 10 µmol / kg / ip, EFAC). Después de las administraciones, se sacrificaron los animales y se extrajeron los tejidos renales. Se evaluaron los cambios histopatológicos y se realizó inmunotinción de TNF-α e IL-6. Además, los niveles tisulares de SOD, CAT y MDA se midieron mediante un ensayo ELISA para evaluar el estrés oxidativo y la peroxidación lipídica. El grupo CP mostró deterioro histopatológico en comparación con el grupo Control y el tratamiento con EFAC atenuó este daño. En comparación con el grupo de control y EFAC, se observó un aumento en las inmunorreactividades de TNF-α e IL-6 y los niveles de MDA en el tejido en el grupo de CP, mientras que se detectó una disminución en los niveles de SOD y CAT en los tejidos. Además, se observó una mejora en el CP + EFAC en comparación con el grupo CP. Sugerimos que EFAC puede utilizarse como agente terapéutico para atenuar los efectos tóxicos del cisplatino, gracias a sus propiedades antioxidantes y antiinflamatorias.

Protective Effects of Caffeic Acid Phenethyl Ester on Isoniazid and Rifampicin-induced Hepatic and Pancreatic Injury

ABSTRACT Objective: To investigate the protective effects of caffeic acid phenethyl ester (CAPE) against isoniazid (INH)- and rifampicin (RFP)-induced hepatic and pancreatic damage. Methods: Eighty adult rats were randomly divided into eight groups: control, INH, RFP, INH+RFP, INH+CAPE, RFP+CAPE, INH+RFP+CAPE, and CAPE. Both INH and RFP were orally administered for 30 days at a dose of 50 mg/kg/day. Caffeic acid phenethyl ester was intraperitoneally injected for 30 days (10 μmol/kg). Blood samples, hepatic and pancreatic tissues were obtained on day 30. Results: Total oxidant status levels were significantly higher in INH and/or RFP-treated groups than those of control and CAPE groups, while total antioxidant status and paraoxonase levels were significantly reduced in INH-RFP groups compared with the group receiving CAPE. Histopathological deterioration was observed in RFP and INH groups in pancreatic and hepatic tissue. However, significant amelioration was observed in CAPE-treated groups. Conclusion: Our findings suggest that CAPE may be a promising agent to prevent the side effects of INH and RFP treatment on hepatic and pancreatic tissues.

Propolis and Caffeic Acid Phenethyl Ester Attenuates Nitrosative Stress in Lens Tissue in Radiation-induced Cataracts in Rats

ABSTRACT Objective: Eye morbidity is widely observed in patients receiving total body irradiation prior to bone marrow transplantation or radiotherapy for ocular or head and neck cancers. Cataract blindness is the major cause of preventable blindness worldwide, especially in the developing countries. The aim of this study was to investigate whether propolis and caffeic acid phenethyl ester (CAPE) prevent radiation-induced cataractogenesis. Methods: Fifty-four Sprague-Dawley rats were randomly divided into six groups. Group 1 (irradiation (IR) + propolis) received total cranium irradiation and propolis was given orally through an orogastric tube daily. Group 2 (IR+CAPE) received total cranium irradiation plus CAPE intraperitoneally every day. Group 3 (IR) received 5 Gy of gamma irradiation as a single dose to total cranium plus 1 ml saline daily. Group 4 received daily plain saline. Group 5 received daily plain dimethyl sulfoxide. Group 6 (normal control group) did not receive anything. Results: At the end of the 10-day time period, cataracts developed in 80% of the rats in group 3 (IR group). After irradiation, cataract rate drop to 30% and 40% in groups treated with propolis and CAPE, respectively. Nitric oxide synthase activity, nitric oxide (NO•) and peroxynitrite (ONOO-) levels were significantly higher in group 3 compared to all other groups. Conclusion: The results suggest that propolis and CAPE have free radical scavenging activities in the irradiation-induced cataractogenesis, and reduced nitrosative stress markers. Prop-olis was found to be more effective in anticataractogenic effect than CAPE.

Propolis polyphenolic compounds affect the viability and structure of Helicobacter pylori in vitro

ABSTRACT To evaluate the anti-Helicobacter pylori activity of the major polyphenol compounds of propolis and their cellular damage, both as single molecule or in combination. Honey bees propolis were fractionated by using CPC and preparative HPLC. Four major polyphenols (chrysin, pinocembrin, galangin and caffeic acid phenethyl ester) were identified by thin layer chromatography-mass spectroscopy and liquid chromatography-mass spectroscopy. These compounds inhibited both ATCC and clinical H. pylori strains, with caffeic acid phenethyl ester being the most active. The four compounds presented minimum inhibitory concentration in the range 256-1024 µg ml−1 and a fractional inhibitory concentration of 64-512 µg ml−1. In mixtures all compounds showed an indifference effect (FIC < 0.15) but chrysin + galangin which was synergistic (FIC = 2.0). Killing curves show a similar behavior as the antibiotic amoxycillin. On the other hand, analyses by transmission electron microscopy at sub inhibitory concentration show vesicle formation and cell lysis after exposition to both individual polyphenol compounds and in mixture. The major compounds of propolis show anti-H. pylori activity both as individual compounds and in mixture. When combined they present mainly indifference but exert a lytic activity upon H. pylori, suggesting a potential bactericidal activity of propolis.

Standardization, anti-carcinogenic potential and biosafety of Indian propolis

Background: Propolis from apiculture is known for wide range of medicinal properties owing to its vastchemical constituents including polyphenols, flavonoids and anticancer agent Caffeic acid phenethylester (CAPE).Objectives: The objective of the study was to extract and standardize Indian propolis (IP) with respect toselected markers by newly developed High performance liquid chromatography (HPLC) method, toevaluate in vitro and in vivo anticancer activity and biosafety of Indian propolis.Materials and methods: IP was extracted, optimized and standardized using a newly developed andvalidated HPLC method for simultaneous estimation of caffeic acid, apigenin, quercetin and CAPE. Thestandardised ethanolic extract of IP (EEIP) was screened for in vitro cytotoxicity using sulforhodamine B(SRB) assay, in vivo anti-carcinogenic effect against Dalton’s Lymphoma ascites (DLA) cells, hemolyticeffect and pesticide analysis.Results: The EEIP was found to contain more amount of total flavonoids (23.61 ± 0.0452 mg equivalent ofquercetin/g), total polyphenolics (34.82 ± 0.0785 mg equivalent of gallic acid/g) and all selected markersexcept caffeic acid compared to all other extracts. EEIP showed better anti-cancer potential than CAPE onMCF-7 and HT-29 cell line and significant (p < 0.01) in vivo anti-carcinogenic effects against DLA incomparison with 5-fluorouracil. EEIP was found to be non-hemolytic.Conclusion: From in vitro cytotoxicity, in vivo anti-carcinogenicity and biosafety studies it can be concludedthat the standardized EEIP is safe and can be considered for further development as a biomedicine.© 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Effects of caffeic acid phenethyl ester on retinal damage after traumatic brain injury / Efectos del ester fenetílico del ácido cafeico en el daño de la retina después de una lesion cerebral traumática

SUMMARY: Head trauma damages the optic nerve visual function and visual acuity.Effects of head trauma on the retina was investigated with biochemical, histological and immunohistochemical respects.The study was conducted on 30 rats with three groups: group 1 was control group (n=10). Second group was head-traumatized group (n=10) and last group was head-traumatized+Caffeic acid phenethyl ester (CAPE, i.p. 20ml/kg/day). Upon head was traumatized, CAPE was applied to trauma+CAPE group and then for the following four days. At the end of 5th day, rats were anesthetized with ketamine hydroxide and then blood samples were taken for biochemical analysis. MDA and GSH-Px values were compared. After blood sample, total eyes of rats were dissected for histopathological and immunohistochemical analysis. In trauma group, degeneration in retinal photoreceptor cells, disintegrity and in inner and outer nuclear layers, hypertrophy in ganglion cells, and hemorrhage in blood vessels were observed. In the group treated with CAPE, lesser degeneration in photoreceptor cells, regular appearances of inner and outer nuclear layers, mild hemorrhage in blood vessels of ganglionic cell layer were observed. The apoptotic changes caused by trauma seen in photoreceptor and ganglionic cells were decreased and cellular organization was preserved due to CAPE treatment. CAPE was thought to induce healing process on traumatic damages.

RESUMEN: El trauma craneal daña la función visual del nervio óptico y la agudeza visual. Se investigaron los efectos del traumatismo craneal en la retina con aspectos bioquímicos, histológicos e inmunohistoquímicos. El estudio se realizó en 30 ratas distribuidas en tres grupos: grupo control (n = 10); grupo con traumatismo craneal (n = 10); grupo con traumatismo craneoencefálico + Éster fenetílico de ácido cafeico (CAPE, i.p. 20 ml / kg / día). Sobre la cabeza traumatizada, se aplicó CAPE a trauma + grupo CAPE durante los siguientes cuatro días. Al final del día 5, las ratas se anestesiaron con hidróxido de ketamina y luego se tomaron muestras de sangre para el análisis bioquímico. Se compararon los valores de MDA y GSH-Px. Después de la muestra de sangre, se disecaron los ojos de las ratas para su análisis histopatológico e inmunohistoquímico. En el grupo de traumatismos, se observó degeneración en las células fotorreceptoras retinianas, desintegridad en capas nucleares internas y externas, hipertrofia en células ganglionares y hemorragia en los vasos sanguíneos. En el grupo tratado con CAPE, se observó una menor degeneración en las células fotorreceptoras, apariciones regulares de capas nucleares internas y externas, hemorragia leve en los vasos sanguíneos de la capa de células ganglionares. Los cambios apoptóticos causados por el trauma visto en el fotorreceptor y las células ganglionares disminuyeron y la organización celular se conservó debido al tratamiento con CAPE. Se concluyó que CAPE induce un proceso de curación en daños traumáticos.

Caffeic acid phenethyl ester protects against photothrombotic cortical ischemic injury in mice

In this study, we aimed to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE), an active component of propolis purified from honeybee hives, on photothrombotic cortical ischemic injury in mice. Permanent focal ischemia was achieved in the medial frontal and somatosensory cortices of anesthetized male C57BL/6 mice by irradiation of the skull with cold light laser in combination with systemic administration of rose bengal. The animals were treated with CAPE (0.5–5 mg/kg, i.p.) twice 1 and 6 h after ischemic insult. CAPE significantly reduced the infarct size as well as the expression of tumor necrosis factor-α, hypoxiainducible factor-1α, monocyte chemoattractant protein-1, interleukin-1α, and indoleamine 2,3-dioxygenase in the cerebral cortex ipsilateral to the photothrombosis. Moreover, it induced an increase in heme oxygenase-1 immunoreactivity and interleukin-10 expression. These results suggest that CAPE exerts a remarkable neuroprotective effect on ischemic brain injury via its anti-inflammatory properties, thereby providing a benefit to the therapy of cerebral infarction.

Protective effect of caffeic acid phenethyl ester (CAPE) on ischemia­ reperfusion injury in rat ovary / Efecto protector de ester feniletílico de ácido cafeico (CAPE) en la lesión por isquemia-reperfusión en ovario de rata

The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) as a prophylactic agent on ischemia/reperfusion (I/R) injury in the rat ovary. A total of 28 Wistar rats were divided into 4 equal groups: (I) sham, (II) ischemia, (III) ischemia + reperfusion, and (IV) IR + CAPE. In groups I and II, ovary torsion was not performed and no drug was administered. In group III, 1 hour of ischemia and 2 hours of reperfusion were performed and no drug was given. Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and Cape groups (P<0.005). The detorsion group showed preantral ovarian follicles and luteal folicules around the blood vessels and positive expression of CD34. In the CAPE group the stromal vascular endothelium with weak expression of CD34 was detected in small areas, and the ovarian follicles and the corpus luteum showed negative expression of CD34. In the study, Biochemical and histopathological results of CAPE treatment was considered to torsion-detorsioned the model showed a protective effect against tissue damage.

El objetivo de este trabajo consistió en investigar los efectos del éster fenetílico del ácido cafeico (EFAC) como agente profiláctico en la lesión por isquemia/reperfusión (I / R) en el ovario de rata. Un total de 28 ratas Wistar se dividieron en 4 grupos iguales: (I) control, (II) isquemia, (III) isquemia + reperfusión, y (IV) IR + EFAC. En los grupos I y II, no se realizó torsión ovárica y no se administró ningún fármaco. En el grupo III, se provocó una hora de isquemia, dos horas de reperfusión y no se administró ningún fármaco. Las concentraciones de malondialdehído en los tejidos ováricos fueron significativamente mayores en los grupos de torsión y de destorsión, en comparación con los grupos sham y de EFAC (P <0,005). El grupo de destorsión mostró folículos ováricos preantrales y folículos lúteos alrededor de los vasos sanguíneos y expresión positiva de CD34. En el grupo EFAC el endotelio vascular estromal con expresión débil de CD34 se detectó en áreas pequeñas, y los folículos ováricos y el cuerpo lúteo mostraron expresión negativa de CD34. En el estudio, fueron considerados los resultados bioquímicos e histopatológicos del tratamiento EFAC en relación a la torsión-destorsión, desarrollando un modelo que mostró un efecto protector contra el daño tisular.

Caffeic Acid Phenethyl Ester Increases Radiosensitivity of Estrogen Receptor-Positive and -Negative Breast Cancer Cells by Prolonging Radiation-Induced DNA Damage / 한국유방암학회지

PURPOSE: Breast cancer is an important cause of death among women. The development of radioresistance in breast cancer leads to recurrence after radiotherapy. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound of honeybee propolis, is known to have anticancer properties. In this study, we examined whether CAPE enhanced the radiation sensitivity of MDA-MB-231 (estrogen receptor-negative) and T47D (estrogen receptor-positive) cell lines. METHODS: The cytotoxic effect of CAPE on MDA-MB-231 and T47D breast cancer cells was evaluated by performing an 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. To assess clonogenic ability, MDA-MB-231 and T47D cells were treated with CAPE (1 µM) for 72 hours before irradiation, and then, a colony assay was performed. A comet assay was used to determine the number of DNA strand breaks at four different times. RESULTS: CAPE decreased the viability of both cell lines in a dose- and time-dependent manner. In the clonogenic assay, pretreatment of cells with CAPE before irradiation significantly reduced the surviving fraction of MDA-MB-231 cells at doses of 6 and 8 Gy. A reduction in the surviving fraction of T47D cells was observed relative to MDA-MB-231 at lower doses of radiation. Additionally, CAPE maintained radiation-induced DNA damage in T47D cells for a longer period than in MDA-MB-231 cells. CONCLUSION: Our results indicate that CAPE impairs DNA damage repair immediately after irradiation. The induction of radiosensitivity by CAPE in radioresistant breast cancer cells may be caused by prolonged DNA damage.

Inhibitory effects of caffeic acid phenethyl ester on inflammatory responses of microglial cells (BV-2) induced by lipopolysaccharide / 中国药学杂志

OBJECTIVE: To investigate the inhibitory effects of caffeic acid phenethyl ester (CAPE) on LPS-induced inflammatory responses in BV-2 microglial cells and its mechanism.

Effect of Caffeic Acid Phenethyl Ester on Lipopolysaccharide-induced Murine Macrophage Activation / 대한구급학회지

BACKGROUND: Caffeic acid phenethyl ester (CAPE) is an active component of propolis and is known to have anti-inflammatory properties. This study was performed to evaluate the effects of CAPE on lipopolysaccharide (LPS)-induced murine macrophage activation. METHODS: Raw 264.7 cells were incubated with varying concentrations of CAPE with or without LPS. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and macrophage inflammatory protein-2 (MIP-2) and activation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun amino terminal kinases (JNK) and p38 were measured. RESULTS: CAPE inhibited the production of TNF-alpha, IL-1beta and MIP-2 and attenuated phosphorylation levels of ERK1/2 and p38, but not JNK in RAW264.7 cells stimulated with LPS. CONCLUSIONS: CAPE can attenuate LPS-induced macrophage responses and we suggest that these effects may play an important role in modulating macrophage-mediated inflammatory responses in vivo.

Estudo da proteção renal durante a isquemia e reperfusão em ratos com o CAPE (caffeic acid phenethyl ester) / A study of kidney protection during ischemia and reperfusion in rats with theCAPE (caffeic acid phenethyl ester)

o CAPE, ativo componente da própolis, é um potente antioxidante com importantes ações no estudo da isquemia e reperfusão renal. O objetivo deste estudo é avaliar o efeito do CAPE na lesão renal de isquemia-reperfusão em ratos anestesiados com isoflurano. Utilizou-se 26 ratos Wistar, machos, com peso superior a 250 g, distribuídos de modo aleatório em três grupos de animais, designados: G1 (controle, isquemia; n = 8); G2 (CAPE + isquemia; n = 10); G3 (diluente do CAPE (etanol) + isquemia; n = 8). Todos os grupos receberam indução da anestesia com isoflurano a 4% e a manutenção com isoflurano de 1,5 a 2,0%. A pressão arterial média (PAM) foi medida para controle da anestesia. A injeção intraperitoneal do CAPE (G2) ou do etanol (G3) foi feita 40 minutos antes da isquemia renal esquerda. Nos três grupos a isquemia durou 25 minutos. Todos os animais foram submetidos à nefrectomia direita. Os valores plasmáticos da creatinina foram determinados no início (M1), no final do experimento (M2) e 24 horas após o final do experimento (M3), quando os animais retornaram ao laboratório e foram anestesiados com isoflurano para coleta de amostra sanguínea e nefrectomia esquerda. Para análise histológica foi utilizada uma escala para avaliação da necrose tubular (0 a 5 = lesão máxima). Houve tratamento estatístico para os valores da temperatura dos animais, peso, PAM, da creatinina plasmática e das lesões histológicas, sendo as diferenças consideradas significantes quando p < 0,05. Conforme mediana, 1o e 3o quartis, entre colchetes, segundo o grupo, a creatinina foi maior em M2 do G2 (0,8 [0,6;0,8]) do que M2 do G1 (0,5[0,4;0,6]) e M2 do G3 (0,6[0,6;0,7]) com p = 0,0012. A creatinina também foi maior em M3 do G2 (3,7 [2,6;4,4]) do que M3 do G1 (0,9[0,7;1,4] e M3 do G3 (1,0[0,9;1,6] com p = 0,0014...

CAPE, an active component of propolis, exhibits antioxidant properties with important actions on ischemia and reperfusion renal study. The purpose of this investigation was to examine the effect of CAPE in renal ischemia/reperfusion in rats anesthetized with isoflurane. Twenty six rats were randomly assigned in three groups: G1 (control, ischemia; n = 8); G2 (CAPE + ischemia; n = 10); G3 (dilute of CAPE (ethanol) + ischemia; n = 8). All groups were anesthetized with isoflurane. Mean arterial pressure (MAP) was monitored for anesthesia control. Intraperitoneal CAPE (G2) or ethanol (G3) injections were realized 40 minutes before left renal ischemia. All animals underwent to right nephrectomy and left kidney was submitted to ischemia for 25 minutes. Serum creatinine values were determined in the beginning (M1) and at the end of experiment (M2) and 24 hours after the experiment (M3) rats were anesthetized with isoflurane and intracardiac blood sample was collected and the left kidney removed for histological analysis, using a scale for tubular necrosis (0-5= injury maximum). Statistical analysis was applied to the values of temperature, weight, MAP, serum creatinine and histological score injury and statistical differences were considered when p<0,05. There were no difference among the temperature of different groups. The weight of G2 were higher than others groups. The PAM of group G3 was higher in M2 than other groups. Creatinine values in M2 of group G2 were higher than M2 of group G1 and M2 of group G3 (p=0.0012) and were higher than M3 of group G1 and M3 of group G3 (p=0.0014). There was no difference of creatinine values in M1 of the three groups (p=0.054)...

Effects of caffeic acid phenethyl ester on the colorectal cancer via the β-catenin pathway / 中华消化外科杂志

Objective To study the effects of caffeic acid phenethyl ester (CAPE) on the expression of β-catenin, c-myc and cyclin D1 in colorectal cancer cell line SW480. Methods The changes of mRNA and protein expression of β-catenin, cyclin DI and c-myc were detected by RT-PCR and Western blot after culturing the colorectal cancer cell line SW400 with different concentrations of CAPE (2.5, 5.0, 10.0 mg/L) for 24 hours and 48 hours. Results After the treatment of CAPE, the mRNA expression of β-catenin, cyclin D1 and c-myc were decreased from 1.05±0. 26, 0.87±0.09, 0.63 ± 0. 09 to 0.67 ±0. 10, 0.51±0.14, 0.32±0.14, respectively, and the protein expression of β-catenin, cyclin D1 and c-myc were decreased from 204±52, 111±11, 87±7 to 52±16, 52±16, 32±12, respectively. There was a significant difference in the decrease of mRNA and protein expression of β-catenin, cyclin D1 and c-myc in colorectal cancer cell line SW480 with and without treatment of CAPE (F=5.724, 6.793, 7.026, 15.936, 14.889, 14.162, 31.147, 28.881, 6.322, 17.647, 9.584, P<0.05 ). The inhibition effect of CAPE was displayed in a dose- and time-dependent manner. Conclusions CAPE can obstruct the β-catenin pathway, and down-regulate the transcription and expression of β-catenin, cyclin D1 and c-myc. The anti-tumor effect of CAPE may be related to the decreased expression of β-catenin, cyclin DI and c-myc.

Caffeic Acid Phenethyl Ester Inhibits the PKC-Induced IL-6 Gene Expression in the Synoviocytes of Rheumatoid Arthritis Patients

To gain insight on the role of pro-inflammatory cytokines in the pathogenesis and treatment of rheumatoid arthritis (RA), the phorbol 12-myristate 13-acetate (PMA) -induced IL-6 gene expression and the effect of caffeic acid phenethyl ester (CAPE) on the PMA-induced IL-6 gene expression were investigated in human fibroblast-like synoviocytes (FLSs). Synovial tissue samples were obtained from rheumatoid arthritis patients, and FLSs were isolated. The cells were stimulated with PMA (100 nM) for 6 hrs to induce IL-6 gene. The cells were pretreated with CAPE (20, 50, 100 microM) prior to PMA treatment. PMA increased IL-6 RNA expression, binding activities of transcription factors (NF-kappaB, AP-1) to IL-6 promoter, and IL-6 promoter activity. However, CAPE inhibited PMA-induced IL-6 mRNA expression in dose-dependent manner, and also inhibited the increased binding activities of transcription factors to IL-6 promoter and IL-6 promoter activity. These results suggest that CAPE might regulate PKC-mediated IL-6 expression and inflammatory reactions in RA.

Effects of caffeic acid phenethyl ester in wnt/?-catenin signaling pathway on human neuroglioma / 重庆医科大学学报

Objective:The therapic effect of caffeic acid phenethyl ester(CAPE) in neuroglioma was to be investigated in this article.Methods:Athymic mouse model was constructed for therapic observation when tumor was treated by CAPE in vivo.Then Real-time PCR was employed to detected the expressing level of c-myc and ?-catenin genes in Wnt/?-catenin signaling pathway when U251 cells were treated by CAPE.Results:CAPE could inhibit the growth of neuroglioma in athymic mouse through drug oral application.The mRNA and protein expression of ?-catenin were inhibited.Furthermore,c-myc gene,which was the downstream of?-catenin gene,was also down-regulated after the drug treatment.Conclusion:The expressing level of ?-catenin and c-myc genes were down-regulated after CAPE treatment, by which the growth of neuroglioma could be inhibited.

Effect of caffeic acid phenethyl ester on the growth of human colorectal carcinoma cell line HCT116 transplanted subcutaneously in nude mice / 解放军医学杂志

Objective To investigate the effect of caffeic acid phenethyl ester (CAPE) on the growth of human colorectal carcinoma cell line HCT116 transplanted subcutaneously in nude mice. Methods Nude mouse model of human colorectal carcinoma by subcutaneous transplantation of HCT116 cell line was reproduced. A total of 20 mice were divided into 2 groups: control group and CAPE group (oral administration of CAPE at 5mg/mice/d). The growth of the subcutaneously transplanted tumor and changes in mouse body weight in each group after treatment were observed on 7, 14, 21 and 28d. Histopathological examination of xenograft, heart, liver, lung, kidney and intestine of nude mice was also conducted. Apoptosis index was detected by terminal dUTP nick end labeling (TUNEL) technique. Results CAPE had significantly inhibitory effect on growth of the transplanted xenograft in vivo. Tumor volume and tumor weight were decreased (P

Effect of caffeic acid phenethyl ester on proliferation and apoptosis of human colorectal cancer cell lines / 中国普通外科杂志

Objective To observe the effect of caffeic acid phenethyl ester (CAPE) on proliferation, cell cycle and apoptosis of human colorectal cancer cell line SW480.MethodsSW480 cells were treated with CAPE .The proliferative status of cells was measured by methabenzthiazuron (MTT) assay. Cell cycle was analyzed by flow cytometry (FCM) . Apoptosis was detected by FCM. The apoptosis cells were detected by TUNEL staining.ResultsCAPE inhibited growth of SW480 cells in a dose-dependent and time-dependent manner. Cell G_0/G_1 phase rate increased, S phase rate decreased and cell apoptosis rate increased after exposed to CAPE in a dose dependent manner (2.5, 5.0 and 10mg/L). Apoptosis cells increased after the treatment of CAPE.ConclusionsCAPE inhibits the proliferation and induces apoptosis in human colon cancer cell line SW480.The effect mechanism is related to arrest the cell cycle G_1 and induce cell apoptosis.

Effect of caffeic acid phenethyl ester on the expression of ?-catenin in the cultured human colorectal cancer cell lines / 第三军医大学学报

Objective To study the effect of caffeic acid phenethyl ester (CAPE) on the expression of ?-catenin in the cultured colorectal cancer cell lines. Methods HCT116 and W480 cells were treated with CAPE at serial concentrations of 2.5, 5, and 10 mg/L. ?-catenin protein expression was assayed by Western blot analysis. ?-catenin localization was detected by indirect immunofluorescence. Results CAPE treatment was associated with decreased total ?-catenin protein expression. The expression of ?-catenin at the cell nucleus and cytoplasm was downregulated, but at the cell-cell linked site the ?-catenin protein expression was upregulated. Conclusion CAPE can downregulate the expression of ?-catenin and inhibit the translocation of ?-catenin to nucleus, which may play an important role in the anticancer activity of CAPE.