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1.
Int. j. morphol ; 39(2): 612-618, abr. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1385340

ABSTRACT

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.


Subject(s)
Animals , Male , Rats , Phenylethyl Alcohol/analogs & derivatives , Caffeic Acids/pharmacology , Cisplatin/toxicity , Kidney/drug effects , Phenylethyl Alcohol/pharmacology , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Rats, Wistar , Oxidative Stress/drug effects , Inflammation , Antineoplastic Agents/toxicity
2.
Braz. arch. biol. technol ; 64: e21190530, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153299

ABSTRACT

HIGHLIGHTS The phenolic composition, antioxidant activity and cytotoxic potential of the extracts of C. solstitialis and U. picroides were investigated. Caffeic acid was found as the most abundant phenolic compound in the extracts. Both species showed promising antioxidant activity towards different assays. The highest cytotoxic potential was observed in the extract of C. solstitialis.


Abstract It is known that some genera of the Asteraceae family are commonly used in Turkish folk medicine. Several studies have investigated the biological effects of different extracts of Centaurea and Urospermum species, but studies involving the phenolic composition of C. solstitialis and U. picroides extracts are very limited. This study aimed to investigate the phenolic composition and antioxidant activity of C. solstitialis and U. picroides and evaluate their possible cytotoxic effect. RP-HPLC analysis was used to elucidate the phenolic profiles of the ethanolic extracts of flowering parts of C. solstitialis and U. picroides.The both ethanolic extracts were assessed for their antioxidant properties using DPPH, FRAP, phosphomolybdenum and metal chelating assays. Furthermore, the effect of the extracts on cell viability was evaluated against MCF-7 and PC-3 cancer cells and HEK293 cell line using the MTT assay. The most abundant phenolic compound in both extracts was determined to be caffeic acid, and the amount of this compound was 24078.03 and 14329.59 µg g-1 in the extracts of C. solstitialis and U. picroides, respectively. The antioxidant activity of the extracts was found similar. Compared with U. picroides extract, C. solstitialis extract had higher potential on the inhibition of cell viability. The IC50 value of C. solstitialis on MCF cells was found as 58.53 µg mL-1. These data suggest that the extracts of C. solstitialis and U. picroides may be considered as novel and alternative natural antioxidant and anticancer sources.


Subject(s)
Humans , Asteraceae/chemistry , Cytotoxins/pharmacology , Centaurea/chemistry , Phenolic Compounds/analysis , Antioxidants/pharmacology , Phenols/pharmacology , Plants, Medicinal , Turkey , Caffeic Acids/pharmacology , Plant Extracts/pharmacology , Chromatography, High Pressure Liquid , HEK293 Cells
3.
Electron. j. biotechnol ; 47: 17-28, sept. 2020. ilus, graf
Article in English | LILACS | ID: biblio-1253006

ABSTRACT

BACKGROUND: Cichoric acid (CA) is extracted from Echinacea purpurea. It is well known and widely used for its immunological function. However, the effect of CA on peripheral blood mononuclear cells (PBMCs) from yaks is still unclear. This study investigated the potential influences of CA on the proliferation, cytokine induction, and apoptosis of PBMCs from Datong yak in vivo, and aimed to provide a basis for exploring the pharmacological activities of CA on yaks. RESULTS: In this study, CA promoted PBMCs proliferation by combining concanavalin A (Con A) and exhibited a dose-dependent effect as demonstrated by a Cell Counting Kit-8. The concentration of 60 µg/ml CA was the best and promoted the transformation from the G0/G1 phase to the S and G2/M phases with Con A. Furthermore, 60 µg/ml CA significantly increased IL-2, IL-6, and IFN-γ levels and PCNA, CDK4 and Bcl-2 expression levels, but it significantly inhibited the TP53, Bax, and Caspase-3 expression levels. Transcriptome analysis revealed a total of 6807 differentially expressed genes (DEGs) between the CA treatment and control groups. Of these genes, 3788 were significantly upregulated and 3019 were downregulated. Gene Ontology and pathway analysis revealed that DEGs were enriched in cell proliferation and immune function signaling pathways. The expression level of some transcription factors (BTB, Ras, RRM_1, and zf-C2H2) and genes (CCNF, CCND1, and CDK4) related to PBMCs proliferation in yaks were significantly promoted after CA treatment. By contrast, anti-proliferation-associated genes (TP53 and CDKN1A) were inhibited. CONCLUSIONS: In summary, CA could regulate the immune function of yaks by promoting proliferation and inhibiting inflammation and apoptosis of PBMCs.


Subject(s)
Animals , Cattle , Succinates/pharmacology , Caffeic Acids/pharmacology , Leukocytes, Mononuclear/drug effects , Echinacea/chemistry , Cell Proliferation/drug effects , Transcription Factors , Enzyme-Linked Immunosorbent Assay , Leukocytes, Mononuclear/cytology , Blotting, Western , Cytokines , Apoptosis/drug effects , Concanavalin A/pharmacology , Real-Time Polymerase Chain Reaction , RNA-Seq
4.
Int. j. morphol ; 38(1): 135-139, Feb. 2020. graf
Article in Spanish | LILACS | ID: biblio-1056411

ABSTRACT

La angiogénesis es el proceso por el cual se forman nuevos vasos sanguíneos a partir de otros ya existentes. Para que esto se lleve a cabo de forma correcta debe existir un balance entre los factores proangiogénicos y los factores antiangiogénicos dentro del microambiente tisular. Por otra parte, la existencia de productos químicos naturales como los polifenoles, que son capaces de adquirirse en la dieta, inducen a estos factores a intervenir en el proceso de angiogénesis. Se administraron los polifenoles en filtros de metilcelulosa sobre la membrana alantocoriónica de huevos White Leghorn, manteniendo el posterior desarrollo normal del feto. Se utilizaron 15 fetos de pollo fijados en formalina tamponada, a los cuales se extrajo el corazón. El procesamiento de las muestras de corazón se realizó a través de técnicas histológicas, histoquímicas e inmunohistoquímica. Finalmente se evaluó la presencia del VEGF y la capacidad de formar vasos sanguíneos bajo el tratamiento con los polifenoles. La inmunorreactividad fue cuantificada mediante Image J®. Los resultados indican que Ácido cafeico y Pinocembrina disminuyen la densidad microvascular y la expresión de VEGF en corazones de fetos de pollo tratados con estos polifenoles. Tanto el Ácido Cafeico como la Pinocembrina cumplen un rol inhibitorio en el proceso de angiogénesis fisiológica en corazón de pollo, pudiendo modular las vías de señalización mediadas por los VEGFR o modulando la disponibilidad de VEGF. Estos polifenoles podrían utilizarse para el estudio de otros tejidos asociados a angiogénesis patológica.


Angiogenesis is the process by which new blood vessels are formed from other existing ones. A balance between proangiogenic factors and anti-angiogenic factors within the microenvironment must exist for the process to be carried out correctly. Similarly, the existence of natural chemicals such as polyphenols, which are capable of being acquired in the diet, induce these factors in the angiogenic process. Polyphenols were administered in the methylcellulose filters on the of chorioallantoic membrane of White Leghorn eggs, maintaining the normal posterior development of the fetus. 15 chicken fetuses were fixed in buffered formalin, obtaining the hearts to histological processing, performing histological, histochemical and immunohistochemical techniques. VEGF levels and the ability of the blood vessels growing under the stimulation of the polyphenols were evaluated. Immunoreactivity was quantified by Image J. The results indicate that caffeic acid and pinocembrin decreased microvascular density and VEGF expression in hearts stimulated with these polyphenols. Both the caffeic and pinocembrin acids play an inhibitory role in the physiological angiogenesis process in the chicken heart, which decrease the microvascular density and could act by modulating the signaling pathways mediated by the VEGFR or by modulating the availability of VEGF. The use of these polyphenols could be useful in studies of other tissues associated with pathological angiogenesis.


Subject(s)
Animals , Caffeic Acids/pharmacology , Neovascularization, Physiologic/drug effects , Chick Embryo , Polyphenols/pharmacology
5.
An. acad. bras. ciênc ; 89(2): 1095-1109, Apr.-June 2017. tab, graf
Article in English | LILACS | ID: biblio-886704

ABSTRACT

ABSTRACT Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.


Subject(s)
Animals , Male , Ascorbic Acid/pharmacology , DNA Damage/drug effects , Caffeic Acids/pharmacology , Cocos/chemistry , Oxidative Stress/drug effects , Ethanol/pharmacology , Liver/drug effects , Time Factors , Triglycerides/blood , Water/pharmacology , Lipid Peroxidation , Cholesterol/blood , Reproducibility of Results , Thiobarbituric Acid Reactive Substances , Rats, Wistar , Tandem Mass Spectrometry , Liver/metabolism , Antioxidants/pharmacology
6.
Int. j. morphol ; 35(1): 141-147, Mar. 2017. ilus
Article in English | LILACS | ID: biblio-840945

ABSTRACT

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.


Subject(s)
Animals , Female , Rats , Caffeic Acids/pharmacology , Ovary/drug effects , Phenylethyl Alcohol/pharmacology , Reperfusion Injury/drug therapy
7.
Braz. j. med. biol. res ; 48(6): 502-508, 06/2015. graf
Article in English | LILACS | ID: lil-748225

ABSTRACT

Hormesis is an adaptive response to a variety of oxidative stresses that renders cells resistant to harmful doses of stressing agents. Caffeic acid (CaA) is an important antioxidant that has protective effects against DNA damage caused by reactive oxygen species (ROS). However, whether CaA-induced protection is a hormetic effect remains unknown, as is the molecular mechanism that is involved. We found that a low concentration (10 μM) of CaA increased human liver L-02 cell viability, attenuated hydrogen peroxide (H2O2)-mediated decreases in cell viability, and decreased the extent of H2O2-induced DNA double-strand breaks (DSBs). In L-02 cells exposed to H2O2, CaA treatment reduced ROS levels, which might have played a protective role. CaA also activated the extracellular signal-regulated kinase (ERK) signal pathway in a time-dependent manner. Inhibition of ERK by its inhibitor U0126 or by its specific small interfering RNA (siRNA) blocked the CaA-induced improvement in cell viability and the protective effects against H2O2-mediated DNA damage. This study adds to the understanding of the antioxidant effects of CaA by identifying a novel molecular mechanism of enhanced cell viability and protection against DNA damage.


Subject(s)
Humans , Antioxidants/pharmacology , Caffeic Acids/pharmacology , Cell Survival/drug effects , DNA Damage/drug effects , Extracellular Signal-Regulated MAP Kinases/drug effects , Reactive Oxygen Species/analysis , Analysis of Variance , Blotting, Western , Cells, Cultured , Cell Line/drug effects , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Liver , Oxidative Stress/drug effects , Reproducibility of Results , Time Factors
8.
Experimental & Molecular Medicine ; : e180-2015.
Article in English | WPRIM | ID: wpr-186437

ABSTRACT

Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), beta-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml-1) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 muM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, beta-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml-1) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 muM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.


Subject(s)
Animals , Rats , Antioxidants/pharmacology , Aorta/cytology , Caffeic Acids/pharmacology , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Leptin/metabolism , Matrix Metalloproteinase 9/metabolism , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/cytology , beta Catenin/metabolism
9.
Rio de Janeiro; s.n; 2012. 75 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-691811

ABSTRACT

Numerosos modelos in vitro e in vivo foram desenvolvidos para estudar o reparo de lesões e identificar os mecanismos chave deste processo. Visando avaliar o processo de cicatrização utilizamos um modelo de lesão excisional total e um modelo de queimadura promovida por escaldamento. No estudo utilizando o modelo de lesão excisional total, abordamos o uso da aspirina (um inibidor não seletivo da COX) e seu efeito diferenciado sobre os sexos na cicatrização cutânea de camundongos. Observamos que os grupos fêmea controle e tratado apresentaram contração atrasada comparado aos grupos macho controle e tratado, respectivamente. Entre os grupos fêmea e macho controles, as fêmeas apresentaram menor atividade da mieloperoxidase e menor quantidade de células MIF-positivas do que os machos controle. Já entre os grupos fêmea e macho tratados, foi observado que nas fêmeas tratadas, a atividade da mieloperoxidase e a quantidade de macrófagos F4/80-positivos estavam maiores do que no grupo macho tratado. Ainda entre os grupos tratados, as fêmeas apresentaram menores níveis de hidroxiprolina e maior expressão proteica de vWF e VEGF comparado aos machos. No estudo das lesões causadas por queimadura, avaliamos as propriedades anti- inflamatórias e antioxidantes do ácido cafeico fenetil ester (CAPE) no reparo destas lesões e observamos que em 7, 14, 21 e 70 dias após a queimadura, o grupo queimado+CAPE apresentou menor área lesada, além de menor atividade da mieloperoxidase e dos níveis de nitrito do que o grupo queimado. Também foi observado que no grupo queimado+CAPE a expressão proteica de CD68 e de PECAM-1 estava reduzida comparada ao grupo queimado. Analisando os parâmetros de dano oxidativo foi observado que os níveis de MDA e de proteínas carboniladas estavam menores no grupo queimado+CAPE do que no grupo queimado, tanto no plasma quanto na lesão. Em suma, nosso estudo avaliou o processo de cicatrização de dois modelos de lesão, em roedores de diferentes espécies ...


Several in vitro and in vivo models have been developed to study wound healing and to identify key mechanisms of this process. The most of these studies use animals models to reproduce the human physiology and possible therapeutic treatments. In order to evaluate the wound healing process in different wound models, we use a full-thickness excisional wound model and a burn model promoted by scalding. In the full-thickness excisional wound study, we approach the aspirin use (COX non-selective inhibitor) and its distinct effect on the gender in cutaneous wound healing on mice. It was observed that both female control and treated groups presented smaller wound area than male control and treated groups, respectively. Between female and male control groups, the females presented smaller myeloperoxidase activity and MIF-positive cells than control males. Comparing female and male treated groups it was observed that in female treated group, the myeloperoxidase activity and the F4/80-positive macrophages amount were greater than male treated group. Also between the treated groups, the females presented smaller hydroxyproline levels and greater vWF and VEGF protein expression compared to the males. In study of the burns performed by scalding, it was evaluated the caffeic acid phenethyl ester (CAPE) anti-inflammatory and antioxidant properties on repair of these lesions. It was observed that at 7, 14, 21 and 70 days after burning, the burn+CAPE group presented smaller wound area, beyond smaller myeloperoxidase activity and nitrite levels than burn group. It was also observed that the burn+CAPE group presented smaller CD68 and PECAM-1 protein expression compared to burn group. Analyzing the oxidative damage parameters, it was observed that the MDA and carbonilated proteins levels were greater in the burn group compared to burn+CAPE group. In conclusion, our study evaluated the wound healing process in 2 wound models on distinct rodent species with distinct approaches ...


Subject(s)
Animals , Mice , Aspirin/therapeutic use , Wound Healing , Skin/injuries , Caffeic Acids/pharmacology , Caffeic Acids/therapeutic use , Phenylethyl Alcohol/analogs & derivatives , Wounds and Injuries/drug therapy , Granulation Tissue , Burns/drug therapy , Sex Factors
10.
Journal of Korean Medical Science ; : 803-810, 2012.
Article in English | WPRIM | ID: wpr-210924

ABSTRACT

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.


Subject(s)
Animals , Rats , Benz(a)Anthracenes/pharmacology , Caffeic Acids/pharmacology , Cells, Cultured , Genistein/pharmacology , Lipoproteins, LDL/metabolism , Lysophosphatidylcholines/pharmacology , Muscle, Smooth, Vascular/cytology , NF-kappa B/antagonists & inhibitors , Oxidative Stress/drug effects , Phenylethyl Alcohol/analogs & derivatives , Plasminogen Activator Inhibitor 1/agonists , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Tissue Plasminogen Activator/metabolism , Transcription, Genetic/drug effects , Up-Regulation/drug effects , Vitamin E/pharmacology
11.
Int. j. morphol ; 28(3): 911-920, Sept. 2010. ilus
Article in English | LILACS | ID: lil-577205

ABSTRACT

Human neutrophils stimulated by phorbol myristate acetate (PMA), an activator of protein kinase C, produce active oxygen by NADPH oxidase in intracellular structures. We added succinimidyl ester of dichlorodihydrofluorescein diacetate (H2DCFDA), which first emits fluorescence when oxidized with active oxygen species, to neutrophils to produce active oxygen, in order to investigate the antioxidant effects of protocatechuic acid, ferulic acid, and caffeic acid which belong to polyphenols and are widely distributed among plants. Particularly, we focused on examining whether these substances capture and eliminate active oxygen inside or outside the neutrophil cytoplasm and whether these substances inhibit NADPH oxidase. Fluorescence microscopy demonstrated that fluorescence-positive intracellular structures were decreased in neutrophils when stimulated by PMA and exposed to an antioxidant. Quantitative measurement by flow cytometry revealed that the fluorescence intensities in neutrophils, exposed to protocatechuic acid, ferulic acid, or caffeic acid, were decreased by 62.9 percent, 71.4 percent, and 86.1 percent, respectively, as compared with those stimulated by PMA but not exposed to an antioxidant. Judging from fluorescence microscopy and dot blots by flow cytometry, these antioxidants had no effects on neutrophil morphology. On the other hand, the fluorescence intensities of the active oxygen released from neutrophils were decreased by 81.4 percent, 46.7 percent, and 27.4 percent, respectively. Diphenylene iodonium, a specific inhibitor of NADPH oxidase, inhibited the enzyme by 92.1 percent in the PMA-stimulated neutrophils. Protocatechuic acid, ferulic acid, and caffeic acid inhibited the enzyme by 36.5 percent, 54.6 percent, and 27.4 percent, respectively. These results demonstrate that protocatechuic acid, ferulic acid, and caffeic acid capture and eliminate active oxygen, produced by PMA-stimulated neutrophils, intracellularly and extracellularly. Furthe...


Los neutrófilos humanos estimulados por forbol-miristato-acetato (PMA), un activador de la proteína quinasa C, producen oxígeno activo por la NADPH oxidasa en las estructuras intracelulares. Hemos añadido diacetato de 2', 7-dihidro dicloro fluoresceína (H2DCFDA), que emite fluorescencia cuando se oxida con las especies de oxígeno activo, a neutrófilos para producir oxígeno activo, a fin de investigar el efecto antioxidante del ácido protocatéquico, el ácido ferúlico y el ácido cafeico que pertenecen a polifenoles y se distribuyen ampliamente entre las plantas. Particularmente, nos enfocamos en examinar si estas sustancias capturan y eliminan el oxígeno activo dentro o fuera del citoplasma de neutrófilos y si estas sustancias inhiben la NADPH oxidasa. La microscopia de fluorescencia demostró que las estructuras intracelulares positivas a fluorescencia disminuyeron en los neutrófilos mediante la estimulación de la PMA y exposición a un antioxidante. La medición cuantitativa por citometría de flujo reveló que la intensidad de fluorescencia en los neutrófilos, expuestos al ácido protocatéquico, el ácido ferúlico, o el ácido cafeico, se redujo un 62,9 por ciento, 71,4 por ciento y 86,1 por ciento, respectivamente, en comparación con las estimuladas por PMA pero no expuestas a un antioxidante. A juzgar desde la microscopía de fluorescencia y la citometría de flujo, estos antioxidantes no tuvieron efectos sobre la morfología de los neutrófilos. Por otra parte, la intensidad de fluorescencia del oxígeno activo liberado por los neutrófilos se redujeron un 81,4 por ciento, 46,7 por ciento y 27,4 por ciento, respectivamente. El DPI (difenileno-iodonio), un inhibidor específico de la NADPH oxidasa, inhibió a la enzima en el 92,1 por ciento en los neutrófilos estimulados por PMA. El ácido protocatéquico, el ácido ferúlico y el ácido caféico inhiben la enzima en un 36,5 por ciento, 54,6 por ciento y 27,4 por ciento, respectivamente. Estos resultados demuestran...


Subject(s)
Antioxidants/pharmacology , Phenols/pharmacology , Neutrophils , Caffeic Acids/pharmacology , Coumaric Acids/pharmacology , Flow Cytometry , Fluorescein , Hydroxybenzoates , Microscopy, Fluorescence , NADPH Oxidases/antagonists & inhibitors , Tetradecanoylphorbol Acetate
12.
Indian J Exp Biol ; 2004 Feb; 42(2): 197-201
Article in English | IMSEAR | ID: sea-55993

ABSTRACT

Quantitative and qualitative analysis of phenolics and boron in stigma of transient sterile Tecoma stans L. during seedless (May-July), partially seedbearing (August-November, April) and seedbearing periods (December-March) was made. UV absorption profile of stigmatic exudates indicated the presence of simple phenolics. Total phenolics were higher in stigma during seedless period. Thin layer chromatographic analysis of stigmatic extracts exhibited only three principal spots. Mass spectrophotometry showed the presence of derivatives of cinnamic acid, namely, caffeic acid in these spots. Quantity of boron in stigma during seedless period was lowest but the difference with other periods was not significant. It was suggested that the accumulation of higher quantity of caffeic acid in the stigma during seedless period due to high temperature (40 degrees-45 degrees C) could lead to inhibition of pollen germination in vivo, thereby rendering the plants seedless. This was confirmed by inhibition of in vitro pollen germination in the basal medium containing higher quantity of caffeic acid.


Subject(s)
Bignoniaceae/cytology , Boron/chemistry , Caffeic Acids/pharmacology , Chromatography, Thin Layer , Cinnamates/analysis , Fertility/drug effects , Flowers/chemistry , Germination/drug effects , Mass Spectrometry , Phenols/chemistry , Pollen/chemistry , Seasons , Seeds/chemistry , Temperature
13.
Indian J Exp Biol ; 1999 Feb; 37(2): 124-30
Article in English | IMSEAR | ID: sea-60835

ABSTRACT

The use of plants is as old as the mankind. Natural products are cheap and claimed to be safe. They are also suitable raw material for production of new synthetic agents. Rosemary (Rosmarinus officinalis Linn.) is a common household plant grown in many parts of the world. It is used for flavouring food, a beverage drink, as well as in cosmetics; in folk.medicine it is used as an antispasmodic in renal colic and dysmenorrhoea, in relieving respiratory disorders and to stimulate growth of hair. Extract of rosemary relaxes smooth muscles of trachea and intestine, and has choleretic, hepatoprotective and antitumerogenic activity. The most important constituents of rosemary are caffeic acid and its derivatives such as rosmarinic acid. These compounds have antioxidant effect. The phenolic compound, rosmarinic acid, obtains one of its phenolic rings from phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl-lactic acid. Relatively large-scale production of rosmarinic acid can be obtained from the cell culture of Coleus blumei Benth when supplied exogenously with phenylalanine and tyrosine. Rosmarinic acid is well absorbed from gastrointestinal tract and from the skin. It increases the production of prostaglandin E2 and reduces the production of leukotriene B4 in human polymorphonuclear leucocytes, and inhibits the complement system. It is concluded that rosemary and its constituents especially caffeic acid derivatives such as rosmarinic acid have a therapeutic potential in treatment or prevention of bronchial asthma, spasmogenic disorders, peptic ulcer, inflammatory diseases, hepatotoxicity, atherosclerosis, ischaemic heart disease, cataract, cancer and poor sperm motility.


Subject(s)
Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Caffeic Acids/pharmacology , Cinnamates/chemistry , Depsides , Female , Humans , Lamiaceae/chemistry , Male , Neuromuscular Agents/pharmacology , Plant Extracts/pharmacology
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