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1.
Braz. j. biol ; 83: e248746, 2023. graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1339351

ABSTRACT

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.


Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.


Subject(s)
Humans , Colorectal Neoplasms/drug therapy , Catechin/analogs & derivatives , Catechin/pharmacology , Quercetin/pharmacology , Cell Cycle , Annexin A5 , Cell Line, Tumor , Cell Proliferation
2.
Int. j. morphol ; 38(4): 876-881, Aug. 2020. graf
Article in English | LILACS | ID: biblio-1124869

ABSTRACT

Acetaminophen (also called paracetamol, or APAP) causes acute kidney injury after accidental or intentional ingestion of a toxic dose of the drug. We tested whether the antioxidant and anti-inflammatory agent, quercetin (QUR) given alone can protect against acute nephrotoxicity induced by APAP overdose in a rat model of APAP-induced acute kidney injury. Rats were either given a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Kidneys were examined by light microscopy after staining with hematoxylin and eosin (H&E) and collected blood samples were assayed for biomarkers of oxidative stress, inflammation, and kidney injury. H&E stained sections of kidney from the model group of rats (APAP) showed substantial damage to the kidney architecture as demonstrated by widening of Bowman's space, tubular dilatation, vacuolization of tubular epithelium, and congested dilated blood vessels, which were partially protected by QUR. In addition, APAP significantly (p<0.05) increased blood levels of urea, creatinine, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6), which were significantly (p<0.05) reduced by QUR. These results indicate that quercetin partially protects against APAP-induced acute kidney injury in rats, which is associated with the inhibition of biomarkers of oxidative stress and inflammation and kidney injury.


El acetaminofeno (también llamado paracetamol o DCI) causa daño renal agudo después de la ingestión accidental o intencional de una dosis tóxica del medicamento. En el estudio analizamos si el agente antioxidante y antiinflamatorio, la quercetina (QUR) administrada sola, puede proteger contra la nefrotoxicidad aguda inducida por sobredosis de DCI en un modelo de rata. Las ratas recibieron una dosis única de DCI (2 g / kg) antes de ser sacrificadas después de 24 horas o fueron pretratadas durante 7 días con QUR (50 mg / kg) antes de recibir una dosis única de DCI y luego sacrificadas 24 horas post ingestión. Los riñones se examinaron mediante microscopía óptica después de la tinción con hematoxilina y eosina (H&E) y las muestras de sangre recolectadas se analizaron para detectar biomarcadores de estrés oxidativo, inflamación y daño renal. Las secciones de riñón teñidas con H&E del grupo modelo de ratas (DCI) mostraron un daño sustancial a la arquitectura del riñón, como lo demuestra la ampliación del espacio de Bowman, la dilatación tubular, la vacuolización del epitelio tubular y los vasos sanguíneos dilatados congestionados, que estaban parcialmente protegidos por QUR. Además, DCI aumentó significativamente (p <0,05) los niveles sanguíneos de la urea, creatinina, malondialdehído (MDA), factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6), los que fueron reducidos significativamente (p < 0,05) por QUR. Estos resultados indican que la quercetina protege parcialmente contra la lesión renal aguda inducida por DCI en ratas, asociada con la inhibición de biomarcadores de estrés oxidativo, inflamación y lesión renal.


Subject(s)
Animals , Rats , Quercetin/administration & dosage , Acute Kidney Injury/chemically induced , Acetaminophen/toxicity , Antioxidants/administration & dosage , Quercetin/pharmacology , Biomarkers/analysis , Oxidative Stress/drug effects , Protective Agents , Creatinine , Disease Models, Animal , Inflammation , Kidney/drug effects , Antioxidants/pharmacology
3.
Arq. bras. cardiol ; 115(1): 102-108, jul. 2020. tab, graf
Article in English, Portuguese | SES-SP, LILACS, SES-SP | ID: biblio-1131269

ABSTRACT

Resumo Fundamento Os glicocorticóides (GCs) são amplamente prescritos para o tratamento de numerosos distúrbios clínicos devido às suas propriedades anti-inflamatórias e imunomoduladoras, e um dos efeitos indesejáveis mais comuns desses medicamentos é a dislipidemia. Objetivo Avaliar o efeito da quercetina, um flavonoide derivado de plantas, no perfil lipídico de ratos tratados com glicocorticóides em altas doses. Métodos Um total de 32 ratos Sprague-Dawley foram distribuídos aleatoriamente entre quatro grupos (8 ratos por grupo) e tratados por 6 semanas com uma das seguintes opções : (i) solução salina normal; (ii) 40 mg/kg de succinato sódico de metilprednisolona (MP); (iii) MP + 50 mg/kg de quercetina; (iv) MP + 150 mg/kg de quercetina. O MP foi injetado por via subcutânea e a quercetina foi administrada por gavagem oral 3 dias por semana. No final do estudo, o perfil lipídico dos animais foi medido através de kits enzimáticos. Os dados foram analisados e a significância estatística foi estabelecida em p <0,05. Resultados Os níveis séricos médios de colesterol total (CT), triglicerídeos (TG) e LDL aumentaram drasticamente em animais tratados com GC em comparação com o grupo controle. Ambas as doses de quercetina (50 e 150 mg/kg) melhoraram o CT (43% e 45%), LDL (56% e 56%) e TG (46% e 55%, respectivamente). A razão Apo B/A1 diminuiu mais de 20% após a ingestão de Anti-Inflamatory Agents. Conclusões Esses dados sugerem que a ingestão de quercetina Quercetin; induzida por glicocorticóides. (Arq Bras Cardiol. 2020; 115(1):102-108)


Abstract Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.)


Subject(s)
Animals , Rats , Quercetin/pharmacology , Glucocorticoids , Apolipoproteins , Triglycerides , Rats, Sprague-Dawley , Lipids
4.
Int. j. morphol ; 38(3): 585-591, June 2020. graf
Article in English | LILACS | ID: biblio-1098291

ABSTRACT

Acetaminophen (also called paracetamol, or APAP) induced nephrotoxicity is reported after accidental or intentional ingestion of an overdose of the drug. Renal tubular ultrastructural alterations induced by APAP overdose associated with the induction of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic anti-inflammatory and antioxidants agents, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced acute kidney injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed one day post APAP ingestion. Harvested kidney tissues were prepared for transmission electron microscopy (TEM) staining and blood samples were assayed for urea, creatinine, and biomarkers of inflammation and oxidative stress. TEM images and blood chemistry analysis showed that APAP overdose induced kidney damage as demonstrated by substantial alterations to the proximal convoluted tubule ultrastructure, and a significant (p<0.05) increase in urea, creatinine, tumor necrosis factor-alpha (TNF-a), and malondialdehyde (MDA) blood levels, which were protected by RES+QUR. These findings indicate that APAP induces alterations to the renal tubular ultrastructure, which is inhibited by resveratrol plus quercetin, which also decreases blood levels of kidney injury biomarkers.


El objetivo de este trabajo fue estudiar la nefrotoxicidad inducida por acetaminofeno (también llamado paracetamol o APAP) después de la ingestión accidental o intencional de una sobredosis de la droga. Las alteraciones ultraestructurales tubulares renales inducidas por sobredosis de APAP asociadas con la inducción de biomarcadores de daño renal no se han investigado. Además, estudiamos si los agentes combinados antiinflamatorios y antioxidantes polifenólicos, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal aguda inducida por APAP. El grupo modelo de ratas recibió una dosis única de APAP (2 g / kg), mientras que el grupo protector de ratas se trató previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg) antes de recibir una dosis única de APAP. Todas las ratas se sacrificaron un día después de la ingestión de APAP. Los tejidos renales fueron preparados para el análisis a través de la microscopía electrónica de transmisión (MET). En las muestras de sangre se determinaron la urea, creatinina y los biomarcadores de inflamación y estrés oxidativo. Las imágenes MET y el análisis químico de la sangre mostraron que la sobredosis de APAP inducía daño renal, como lo demuestran las alteraciones sustanciales en la ultraestructura del túbulo contorneado proximal, y además, de un aumento significativo (p <0,05) de la urea, creatinina, factor de necrosis tumoral alfa y niveles sanguíneos de malondialdehído, protegidos por RES + QUR. Estos hallazgos indican que APAP induce alteraciones en la ultraestructura tubular renal, inhibida por el resveratrol más quercetina, que también disminuye los niveles sanguíneos de biomarcadores de daño renal.


Subject(s)
Animals , Rats , Quercetin/administration & dosage , Resveratrol/administration & dosage , Kidney Tubules/drug effects , Acetaminophen/toxicity , Quercetin/pharmacology , Urea/blood , Rats, Sprague-Dawley , Creatinine/blood , Microscopy, Electron, Transmission , Disease Models, Animal , Drug Overdose , Resveratrol/pharmacology , Kidney Tubules/pathology , Anti-Inflammatory Agents/administration & dosage , Antioxidants/administration & dosage
5.
Int. j. morphol ; 38(1): 83-90, Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056402

ABSTRACT

We sought to determine whether the combined polyphenolic compounds, resveratrol and quercetin can substantially protect against modulation of hepatic biomarkers of apoptosis and survival, p53-Bax axis and B-cell lymphoma 2 (Bcl-2) in an animal model of acetaminophen-induced acute liver injury via the association of oxidative stress and interleukin-11 (IL-11). The model group of rats received a single dose of acetaminophen (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of resveratrol (30 mg/kg) and quercetin (50 mg/kg) before being given a single dose of acetaminophen. All rats were then sacrificed 24 hours post acetaminophen ingestion. Acetaminophen overdose induced acute liver injury as demonstrated by profound liver parenchymal damage and increased levels of the liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Acetaminophen significantly (p<0.05) modulated malondialdehyde (MDA), p53, apoptosis regulator Bax, Bcl-2, IL-11, interleukin-6 (IL-6), ALT, AST, superoxide dismutase (SOD), and glutathione peroxidase (GPx), which were significantly protected by resveratrol plus quercetin. We further demonstrated a significant (p<0.01) correlation between IL-11 scoring and the levels of p53, Bax, Bcl-2, and MDA. Thus, resveratrol plus quercetin effectively protect against acetaminophen-induced apoptosis, which is associated with the inhibition of oxidative stress and IL-11.


En el estudio se intentó determinar si los compuestos polifenólicos combinados, el resveratrol y la quercetina pueden proteger sustancialmente contra la modulación de los biomarcadores hepáticos de apoptosis y supervivencia, el eje p53-Bax y el linfoma de células B 2 (Bcl-2) en un modelo animal de lesión hepática aguda inducida por acetaminofén, a través de la asociación del estrés oxidativo y la interleucina-11 (IL-11). El grupo modelo de ratas recibió una dosis única de acetaminofén (2 g / kg), mientras que el grupo protector de ratas fue tratado durante 7 días con dosis combinadas de resveratrol (30 mg / kg) y quercetina (50 mg / kg) antes de recibir una dosis única de acetaminofén. Todas los animales fueron sacrificados 24 horas después de la ingestión de acetaminofén. La sobredosis de acetaminofén indujo una lesión hepática aguda, como se observó en el daño profundo del parénquima hepático y el aumento de los niveles de las enzimas en la lesión hepática, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Acetaminofén moduló significativamente (p <0.05) malondialdehído (MDA), p53, regulador de apoptosis Bax, Bcl2, IL-11, interleucina-6 (IL-6), ALT, AST, superóxido dismutasa (SOD) y glutatión peroxidasa ( GPx), los que se encontraron significativamente protegidos por el resveratrol y quercetina. Además se determinó una correlación significativa (p <0.01) entre la puntuación de IL-11 y los niveles de p53, Bax, Bcl-2 y MDA. En conclusión, el resveratrol más la quercetina protegen de manera efectiva contra la apoptosis inducida por acetaminofén, asociada con la inhibición del estrés oxidativo y la IL-11.


Subject(s)
Animals , Rats , Quercetin/administration & dosage , Apoptosis/drug effects , Chemical and Drug Induced Liver Injury, Chronic/pathology , Resveratrol/administration & dosage , Acetaminophen/toxicity , Antioxidants/administration & dosage , Quercetin/pharmacology , Aspartate Aminotransferases/analysis , Biomarkers , Interleukin-1 , Oxidative Stress , Alanine Transaminase/analysis , Disease Models, Animal , Chemical and Drug Induced Liver Injury/enzymology , Resveratrol/pharmacology , Antioxidants/pharmacology
6.
Article in English | WPRIM | ID: wpr-881038

ABSTRACT

Due to the poor repair ability of cartilage tissue, regenerative medicine still faces great challenges in the repair of large articular cartilage defects. Quercetin is widely applied as a traditional Chinese medicine in tissue regeneration including liver, bone and skin tissues. However, the evidence for its effects and internal mechanisms for cartilage regeneration are limited. In the present study, the effects of quercetin on chondrocyte function were systematically evaluated by CCK8 assay, PCR assay, cartilaginous matrix staining assays, immunofluorescence assay, and western blotting. The results showed that quercetin significantly up-regulated the expression of chondrogenesis genes and stimulated the secretion of GAG (glycosaminoglycan) through activating the ERK, P38 and AKT signalling pathways in a dose-dependent manner. Furthermore, in vivo experiments revealed that quercetin-loaded silk protein scaffolds dramatically stimulated the formation of new cartilage-like tissue with higher histological scores in rat femoral cartilage defects. These data suggest that quercetin can effectively stimulate chondrogenesis in vitro and in vivo, demonstrating the potential application of quercetin in the regeneration of cartilage defects.


Subject(s)
Animals , Cartilage/cytology , Chondrocytes/drug effects , Chondrogenesis/drug effects , Extracellular Matrix/metabolism , Quercetin/pharmacology , Rats , Signal Transduction/drug effects , Tissue Scaffolds
7.
Int. j. morphol ; 37(4): 1422-1428, Dec. 2019. graf
Article in English | LILACS | ID: biblio-1040148

ABSTRACT

Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the combined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced by a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and superoxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vacuolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNF-α, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNF-α, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r= - 0.7870). We conclude that resveratrol plus quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidants and inhibition of oxidative stress and inflammation.


La sobredosis de paracetamol (también llamado acetaminofen o APAP) causa un daño agudo en el hígado y los riñones, tanto en humanos como en modelos animales experimentales, a través de la inducción de la vía del estrés oxidativo. Intentamos determinar si los antioxidantes y los compuestos antiinflamatorios combinados, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal inducida por una dosis tóxica de APAP en un modelo de rata de lesión renal aguda inducida por APAP. Las ratas recibieron una dosis única de APAP (2 g / kg) antes de ser sacrificadas después de 24 horas o se trataron previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg), antes de ser tratadas, se administró una dosis única de APAP y luego fueron sacrificadas 24 horas después de la ingestión. Los tejidos renales recolectados se tiñeron con H-E y fueron observados a través de microscopía óptica. Las muestras de tejido se analizaron para (i) biomarcadores de estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (ii) biomarcadores de inflamación, factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6). Las imágenes teñidas con H & E mostraron que la sobredosis de APAP indujo daño renal agudo como lo demuestra la ampliación del espacio glomerular, la dilatación tubular, numerosos desechos celulares en los túbulos renales con degeneración epitelial tubular y la vacuolización, que se protegieron eficazmente con RES + QUR Se observó una protección parcial del espacio glomerular. Además, APAP modificó significativamente (p <0.05) los niveles tisulares de MDA, SOD, TNF-α e IL-6, que estaban protegidos por RES + QUR. Además, se observó una correlación positiva significativa (p <0,0001) entre el espacio glomerular y el TNF-α, (r = 0,8899), IL-6 (r = 0,8986) y MDA (r = 0,8552), mientras que la puntuación del espacio glomerular versus SOD mostró correlación negativa (r = - 0,7870). Concluimos que el resveratrol más quercetina protege sustancialmente contra la lesión renal aguda inducida por APAP en ratas, posiblemente a través del aumento de antioxidantes y la inhibición del estrés oxidativo y la inflamación.


Subject(s)
Animals , Rats , Quercetin/therapeutic use , Acute Kidney Injury/drug therapy , Resveratrol/therapeutic use , Acetaminophen/toxicity , Quercetin/pharmacology , Oxidative Stress/drug effects , Disease Models, Animal , Drug Therapy, Combination , Acute Kidney Injury/chemically induced , Resveratrol/pharmacology , Acetaminophen/antagonists & inhibitors , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use
8.
São Paulo; s.n; s.n; 2019. 102 p. graf, tab, ilus.
Thesis in English | LILACS | ID: biblio-1023978

ABSTRACT

Ultraviolet radiation (UV) is related to the development of skin cancer and photoaging, also produces free radicals or reactive oxygen species (ROS) that cause premature aging. Therefore, sunscreens with extended UV protection capacity have been studied associated with antioxidant compounds. Different components can be incorporated with the purpose of improving, the photoprotection efficiency, as well as other cosmetic attributes, creating a multifunctional product. Among the compounds, there are some to be used from natural origin that are excellent, because it reduces the side effects and toxicity. Flavonoids are good examples of natural agents, because have demonstrated photoprotective antioxidant action in food and it is also promising for topical use. The aim of this work is to develop photoprotective formulations with quercetin, evaluating potential photoprotective and antioxidant of each formulation through tests already established and described in the literature, with emphasis on in vitro testing of potential photoprotective, antioxidant and security (het-cam); ex vivo antioxidant potential (tape-stripping). The results show us the photoprotective and antioxidant capacity of quercetin and the ideal concentration for this potential, thereby contributing to the synthesis of new molecules and development of new products, concerning stable, safe and effective exposure to solar UV radiation, preventing new incidences of skin cancer and reduction of photoaging


A radiação ultravioleta (UV) está relacionada ao desenvolvimento de câncer de pele e fotoenvelhecimento, também produz radicais livres ou espécies reativas de oxigênio (EROs) que causam o envelhecimento precoce. Portanto, protetores solares com capacidade de proteção UV amplo espectro foram estudados associados a compostos antioxidantes. Diferentes componentes podem ser incorporados com o objetivo de melhorar a eficiência da fotoproteção, assim como outros atributos cosméticos criando um produto multifuncional. Entre os compostos a serem utilizados, de origem natural são excelentes, pois reduzem os efeitos colaterais e a toxicidade. Os flavonóides são bons exemplos de agentes naturais, porque demonstraram ação antioxidante fotoprotetora nos alimentos e também são promissores para uso tópico. O objetivo deste trabalho é desenvolver formulações fotoprotetoras com quercetina, avaliando potenciais fotoprotetores e antioxidantes de cada formulação através de testes já estabelecidos e descritos na literatura com ênfase em ensaios in vitro de potenciais fotoprotetores, antioxidantes e de segurança (het-cam); potencial antioxidante ex vivo (tape-stripping). Os resultados nos mostram a capacidade fotoprotetora e antioxidante da quercetina e a concentração ideal para este potencial, contribuindo para a síntese de novas moléculas e desenvolvimento de novos produtos estáveis, seguros e eficazes em relação à exposição à radiação solar UV, prevenindo novas incidências de câncer de pele e redução do fotoenvelhecimento


Subject(s)
Quercetin/pharmacology , Sunscreening Agents/analysis , Ultraviolet Rays/adverse effects , Flavonoids/agonists , In Vitro Techniques/instrumentation , Skin Aging , Antioxidants/analysis
9.
Acta cir. bras ; 32(8): 633-640, Aug. 2017. graf
Article in English | LILACS | ID: biblio-886223

ABSTRACT

Abstract Purpose: To evaluate the effect of hyperin in cisplatin-induced liver injury in mice. Methods: Mice were pretreated with hyperin at doses of 25 mg/kg and 50 mg/kg, respectively, for six days, and intraperitoneal injection of cisplatin (40 mg/kg) was administrated one hour after the final intragastrication of hyperin. Twenty-four hours later, blood and liver were collected for further research. Results: A single injection of cisplatin (40 mg/kg) for 24 h significantly increased serum alanine and aspartate aminotransferases (ALT/AST) and gamma glutamyl transferase (GGT) activities, whileas hyperin reversed cisplatin-induced such increases. Liver histopathological examination further demonstrated the protection of hyperin against cisplatin-induced liver injury. Further results showed hyperin reversed cisplatin-induced the increase in content of malondialdehyde (MDA) and the decrease in level of total antioxidant capacity (T-AOC) in liver. Moreover, hyperin increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s transferase (GST) in cisplatin-induced liver. Conclusion: Hyperin inhibits cisplatin-induced hepatic oxidative stress, which contributes greatly to the amelioration of cisplatin-induced liver injury in mice.


Subject(s)
Animals , Male , Quercetin/analogs & derivatives , Aspartate Aminotransferases/metabolism , Cisplatin/adverse effects , Chemical and Drug Induced Liver Injury/prevention & control , Antineoplastic Agents/adverse effects , Antioxidants/pharmacology , Quercetin/therapeutic use , Quercetin/pharmacology , Reference Values , Lipid Peroxidation , Catalase/analysis , Random Allocation , Reproducibility of Results , Cisplatin/antagonists & inhibitors , Oxidative Stress/drug effects , Alanine Transaminase/metabolism , Chemical and Drug Induced Liver Injury/pathology , Glutathione/analysis , Glutathione Peroxidase/analysis , Glutathione Transferase/analysis , Liver/drug effects , Liver/enzymology , Liver/pathology , Malondialdehyde/analysis , Mice, Inbred ICR , Antioxidants/therapeutic use
10.
Braz. j. biol ; 76(4): 1029-1034, Oct.-Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-828088

ABSTRACT

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.


Resumo A anfotericina B é uma substância fungicida e é o tratamento de escolha para a maioria das infecções fúngicas sistêmicas que afetam os pacientes imunocomprometidos, como a criptococose. No entanto, as severas reações adversas têm limitado a utilização desta droga. O objetivo deste estudo foi avaliar o efeito antifúngico e o potencial efeito protetor de citotoxicidade da combinação de anfotericina B com quercetina ou rutina. A atividade antifúngica de anfotericina B, quercetina e rutina, isoladamente e em combinação foi determinada em cepas de Candida sp e Cryptococcus neoformans. O teste de citotoxicidade em eritrócitos foi realizado por espectrofotometria, através da determinação da absorbância da hemoglobina. A concentração inibitória mínima da anfotericina B foi reduzida quando utilizada em combinação com a quercetina e rutina em C. neoformans ATCC e reduzida quando combinados com rutina em um isolado clínico de C. neoformans. Além disso, a combinação de quercetina com anfotericina B pode reduzir a toxicidade da droga em eritrócitos. Os resultados sugerem que quercetina e rutina são potenciais agentes para combinação com anfotericina B, a fim de reduzir a dose de anfotericina, diminuindo os efeitos colaterais e melhorando sua eficácia antifúngica.


Subject(s)
Quercetin/pharmacology , Rutin/pharmacology , Candida/drug effects , Amphotericin B/pharmacology , Cryptococcus neoformans/drug effects , Antifungal Agents/pharmacology , Candida/growth & development , Microbial Sensitivity Tests , Cryptococcus neoformans/growth & development
11.
Braz. dent. j ; 25(6): 554-560, Nov-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-732259

ABSTRACT

The aim of this study was to assess, by the three-dimensional finite element method, the influence of crown-to-implant ratio and parafunctional occlusal loading on stress distribution in single external hexagon implant-supported prosthesis. Computer-aided design software was used to confection three models. Each model was composed of a block bone and an external hexagon implant (5x10.0 mm) with screw-retained implant prostheses, varying the height crown: 10, 12.5 and 15 mm. Finite element analysis software was used to generate the finite element mesh and to establish the loading and boundary conditions. Normal (200 N axial and 100 N oblique load) and parafunctional forces (1,000 N axial and 500 N oblique load) were applied. The results were visualized by von Mises and maximum principal stress. In comparison with the normal occlusal force, the parafunctional occlusal force induced an increase in stress concentration and magnitude on implant (platform and first threads) and screw (neck). The cortical bone showed the highest tensile stress under parafunctional force (oblique load). The stress concentration increased as the crown height increased. It was concluded that: increasing the C/I increased stress concentration in both implant components and cortical bone; parafunctional loading increased between 4-5 times the value of stresses in bone tissue compared with functional loading; the type of loading variation factor is more influential than the crown-to-implant factor.


O objetivo deste estudo foi avaliar, através do método dos elementos finitos tridimensionais, a influência do carregamento oclusal parafuncional e da altura da coroa na distribuição das tensões em próteses unitárias implantossuportadas de hexágono externo. Foram confeccionados três modelos com o auxílio de programas de desenho assistido. Cada modelo foi composto por um bloco ósseo da região molar mandibular, por um implante de tipo hexágono externo (5x10,0 mm) e por coroa com diferentes alturas: 10, 12,5 e 15 mm. Os modelos foram exportados para o programa de elementos finitos NEiNastran 9.0, para geração das malhas e estabelecer as condições de contorno. Aplicou-se uma carga funcional (200 N axial e 100 N oblíqua), bem como uma carga parafuncional (1.000 N axial e 500 N oblíqua). Os resultados foram visualizados por meio de mapas de Tensão de von Mises e mapas de Tensão Máxima Principal. O carregamento parafuncional induziu um aumento da área de distribuição e da magnitude das tensões no implante (plataforma e primeiras roscas) e parafuso (pescoço) em comparação com o carregamento funcional. A cortical óssea apresentou maiores áreas de tensão por tração sob carregamento parafuncional oblíquo. A concentração de tensões aumentou à medida que aumentou a altura da coroa. O aumento da altura da coroa induziu um aumento na concentração de tensões, tanto nos componentes do implante, quanto na cortical óssea; o carregamento parafuncional induziu um aumento entre 4-5 vezes da magnitude das tensões no tecido ósseo; o tipo de carregamento apresenta-se como um fator de variação mais influente do que a proporção coroa/implante.


Subject(s)
Animals , Male , Rats , Flavonoids/pharmacology , Hemodynamics/drug effects , Quercetin/pharmacology , /antagonists & inhibitors , Blood Pressure/drug effects , Dioxolanes/pharmacology , Heart Rate/drug effects , Infusions, Intravenous , Injections, Intravenous , Parasympatholytics , Quercetin/analogs & derivatives , Rats, Inbred Strains , Time Factors
12.
Rev. bras. plantas med ; 16(3): 566-573, jul.-set. 2014. tab
Article in Portuguese | LILACS | ID: lil-722278

ABSTRACT

A carqueja (Baccharis trimera) é uma espécie da família Asteraceae muito utilizada na medicina popular por apresentar várias atividades biológicas relacionadas à seus metabólitos secundários, entre eles os flavonoides. Este experimento teve como objetivo avaliar os efeitos de preparados homeopáticos e do ambiente de cultivo na produção e rendimento de flavonoides totais expressos em quercetina por plantas de carqueja. Foi adotado o esquema fatorial 6 x 2 no delineamento inteiramente casualisado, sendo 5 tratamentos homeopáticos: Silicea CH6, CH12, CH30, D7 e Equisetum D7 e controle (etanol 70%) x 2 ambientes de cultivo: estufa e tela de sombreamento 50%, com 4 repetições, totalizando 48 unidades experimentais. Os tratamentos homeopáticos foram aplicados na concentração de 25 gotas/500 mL de água destilada usando borrifadores manuais. Cada planta recebeu 10 mL da solução por aplicação, via foliar. As aplicações foram realizadas sempre pela manha, três vezes por semana, em dias alternados, durante dois meses (27/07/2010 a 27/09/2010). A interação entre os fatores, assim como os fatores independentes foram comparados pelo teste Tukey a 5% de probabilidade. O efeito dos preparados homeopáticos e dos dois ambientes de cultivo em plantas de carqueja foi avaliado pelas variáveis: massa fresca (MFPA), massa seca (MSPA) e teor de quercetina (QCT) na parte aérea das plantas. As variáveis MFPA e QCT foram influenciadas pelos ambientes de cultivo, pelos preparados homeopáticos e pela interação entre os dois fatores. A variável MSPA foi influenciada apenas pela interação dos fatores. Plantas cultivadas em ambiente com 50% de sombreamento associadas à aplicação dos preparados homeopáti-cos Silicea CH6 e D7, apresentaram maior rendimento em querceti-na. Plantas cultivadas na estufa associadas à aplicação do Equisetum D7 apresentaram menor rendimento em quercetina.


The carqueja plant (Baccharis trimera) is a specie of the family Asteraceae widely used in folk medicine for presenting various biological activities, due to the high content of secondary metabolites, including flavonoids. The objective of this study was to evaluate the effect of homeopathic preparations and crop environments through production and yield of quercetina on carqueja plants. The experiment was a factorial scheme (6X2) on completely randomized design with 5 homeopathic treatments: Silicea CH6, CH12, CH30, D7 and Equisetum D7 e control (70% ethanol) x 2 crop environments: greenhouse and shade 50% and 4 replicates, totaling 48 experimental units. The treatments were applied at concentration of 25 drops/500 mL of distilled water using hand sprayers. Each plant received 10 mL via leaves. The prepara-tions were sprayed always on mornings, three times a week on alternate days during two months (27/09/2010 to 27/11/2010). The interaction between the factors as well as the independents factors were compared by the Tukey test at 5% probability. The effect of homeopathic preparations and the two crop environments on carqueja plants were evaluated through the variables: fresh matter of aerial part (FMAP), dry matter of aerial part (DMAP) and flavonoids content (QCT). The variables FMAP and QCT were significantly influenced by the crop environments, the preparations and interaction between the two factors. The DMAP was only influenced by the interaction of the two factors. The 50% shade environment associated with Silicea CH6 or D7 increased yield of quercetin. The greenhouse environment associated with Equisetum D7 decreased yield of quercetin.


Subject(s)
Baccharis/metabolism , Homeopathy/methods , Quercetin/pharmacology , Equisetum , Silicea Terra
13.
Braz. j. med. biol. res ; 47(8): 655-661, 08/2014. tab, graf
Article in English | LILACS | ID: lil-716268

ABSTRACT

Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.


Subject(s)
Animals , Female , Antioxidants/administration & dosage , Hepatitis/drug therapy , Liver Cirrhosis/drug therapy , Quercetin/pharmacology , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Concanavalin A , Collagen/analysis , Disease Models, Animal , Hepatic Stellate Cells/drug effects , Hepatic Stellate Cells/metabolism , Liposomes , Liver Cirrhosis/chemically induced , Mice, Inbred BALB C , Mitogens , NF-kappa B/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta/metabolism
14.
Braz. j. med. biol. res ; 46(10): 861-867, 24/set. 2013. graf
Article in English | LILACS | ID: lil-688556

ABSTRACT

Quercetin (Que), a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R) injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group): sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P<0.05). Apoptotic cardiomyocytes and caspase-3 immunoreactivity were also suppressed in the Que postconditioning group compared with the I/R group (both P<0.05). Akt phosphorylation and Bcl-2 expression increased after Que postconditioning, but Bax expression decreased. These effects were inhibited by LY294002. The data indicate that Que postconditioning can induce cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.


Subject(s)
Animals , Male , Myocardial Reperfusion Injury/prevention & control , /physiology , Proto-Oncogene Proteins c-akt/physiology , Quercetin/pharmacology , Signal Transduction/physiology , Apoptosis/drug effects , In Situ Nick-End Labeling , Random Allocation , Rats, Sprague-Dawley
15.
Indian J Exp Biol ; 2013 Jan; 51(1): 65-72
Article in English | IMSEAR | ID: sea-147569

ABSTRACT

Antihyperglycemic potential of hyperin at 25 and 50 mg/kg doses for 30 days to streptozotocin induced diabetic rats has been reported. In oral glucose tolerance test, hyperin treated rats showed a significant reduction in blood glucose level after 120 min. It was found that hyperin exhibited dose dependent and significant antihyperglycemic activity in streptozotocin induced diabetic rats which were nearly similar with standard drug glybenclamide. Activities of glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, glycosylated haemoglobin and level of serum urea and creatinine were significantly decreased in hyperin supplemented diabetic rats, dose dependently. Activities of hexokinase and glycogen synthase were increased with augmentation in liver glycogen, insulin and haemoglobin content in hyperin treated diabetic rats. General hematological parameters did not show any significant change in hyperin treated diabetic rats hence it is safe at these doses. Histopathological studies showed significant morphological changes in pancreatic β-cells of streptozotocin induced diabetic rats. A decreased number of secretory granules of β- cells were observed in diabetic rats and these pathological abnormalities were normalized after treatment with hyperin and standard drug glybenclamide. Further, hyperin decreases significant in serum total cholesterol, triglyceride, low density lipoprotein, very low density lipoprotein levels coupled with elevation of high density lipoprotein in diabetic rats. These results suggest that hyperin has a pivotal role in blood glucose level in streptozotocin induced hyperglycemia by improving the function of pancreatic islets and increasing glycolysis and decreasing gluconeogenesis.


Subject(s)
Animals , Diabetes Mellitus, Experimental/drug therapy , Glucose Tolerance Test , Glyburide/pharmacology , Glycogen/metabolism , Hexokinase/metabolism , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Lipids/chemistry , Liver/metabolism , Male , Models, Chemical , Quercetin/analogs & derivatives , Quercetin/chemistry , Quercetin/metabolism , Quercetin/pharmacology , Rats , Rats, Wistar , Rhododendron/metabolism
16.
Gut and Liver ; : 739-746, 2013.
Article in English | WPRIM | ID: wpr-209550

ABSTRACT

BACKGROUND/AIMS: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. METHODS: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. RESULTS: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. CONCLUSIONS: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Caspase 3/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm/drug effects , HSP70 Heat-Shock Proteins/metabolism , Humans , Microtubule-Associated Proteins/metabolism , Pancreatic Neoplasms/drug therapy , Quercetin/pharmacology
17.
Article in English | WPRIM | ID: wpr-31559

ABSTRACT

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.


Subject(s)
Antigens, CD/metabolism , Antineoplastic Agents/pharmacology , Carcinoma, Embryonal/drug therapy , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Flavonoids/pharmacology , Gene Expression Regulation, Neoplastic , Genistein/pharmacology , Humans , Kaempferols/pharmacology , Models, Biological , Phenols/pharmacology , Quercetin/pharmacology , Resorcinols/pharmacology , Stilbenes/pharmacology , Symporters/metabolism , Thyroid Neoplasms/drug therapy
18.
Biol. Res ; 43(4): 429-437, 2010. ilus
Article in English | LILACS | ID: lil-582857

ABSTRACT

Onion (Allium cepa) is being studied as a potential anticancer agent, but little is known regarding its effect in multidrug resistance (MDR) cells. In this work, the cytotoxicity of crude onion extract (OE) and fractioned extract (aqueous, methanolic and ethyl acetate), as well as some onion compounds (quercetin and propyl disulfide) were evaluated in Lucena MDR human erythroleukemic and its K562 parental cell line. The capacity of OE to induce apoptosis and/or necrosis in these cells, the possible participation of oxidative stress and DNA damage were also assessed. Similar sensitivities were obtained for both tumoral cells, however only OE caused significant effects in the cells. In K562 cells, a significant increase of apoptosis was verified while the Lucena cells experienced a significant increase of necrosis. An antioxidant capacity was verified for OE discarding oxidative damage. However, OE provoked similar significant DNA damage in both cell lines. Thus, the OE capacity to overcome the MDR phenotype suggests anti-MDR action of OE.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Drug Resistance, Neoplasm/drug effects , Onions/chemistry , Plant Extracts/pharmacology , Apoptosis , DNA Damage , Disulfides/analysis , Disulfides/pharmacology , /drug effects , Necrosis , Phenotype , Quercetin/analysis , Quercetin/pharmacology , Time Factors
19.
Article in English | IMSEAR | ID: sea-135803

ABSTRACT

Background & objectives: Plant polyphenols have been known to exert anti-diabetic action and promote insulin action. The present study was carried out to compare the effects of administration of fenugreek seed polyphenolic extract (FPEt), quercetin and metformin (a positive control) in an acquired model of insulin resistance (IR). Methods: Adult male Wistar rats divided into seven groups (n=12). IR was induced in groups (groups 2, 3, 4 and 5) by feeding a high fructose diet (FRU) (60 g/100 g diet) for 60 days. From day 16, FRU rats were administered either FPEt (200 mg/kg bw) (group 3), quercetin (50mg/kg bw) (group 4) or metformin (50 mg/kg bw) (group 5) for the next 45 days. Group 1 served as normal control while groups 6 and 7 served as FPEt and quercetin controls respectively. Oral glucose tolerance test (OGTT) was done on day 59 to assess glucose tolerance. At the end of 60 days, the levels of glucose, insulin, triglycerides (TG) and free fatty acids (FFA) were measured in the blood and the activities of insulin-inducible and suppressible enzymes in cytosolic and mitochondrial fractions of liver and skeletal muscle. The extent of tyrosine phosphorylation of proteins in response to insulin was determined by assaying protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in liver. Results: Fructose caused increased levels of glucose, insulin, TG and FFA, alterations in insulin sensitivity indices, enzyme activities and reduced glycogen content. Higher PTP activity and lower PTK activity suggest reduced tyrosine phosphorylation status. Administration of FPEt or quercetin improved insulin sensitivity and tyrosine phosphorylation in fructose-fed animals and the effect was comparable with that of metformin. Interpretation & conclusions: Our findings indicated that FPEt and quercetin improved insulin signaling and sensitivity and thereby promoted the cellular actions of insulin in this model.


Subject(s)
Animals , Blood Glucose , Fatty Acids, Nonesterified/blood , Flavonoids/pharmacology , Fructose/administration & dosage , Glucose Tolerance Test , Insulin/blood , Insulin Resistance/physiology , Liver/metabolism , Male , Metformin/pharmacology , Phenols/pharmacology , Plant Extracts/pharmacology , Polyphenols , Protein Tyrosine Phosphatases/metabolism , Protein-Tyrosine Kinases/metabolism , Quercetin/pharmacology , Rats , Rats, Wistar , Seeds/chemistry , Triglycerides/blood , Trigonella/chemistry
20.
Article in English | WPRIM | ID: wpr-174318

ABSTRACT

Hu protein R (HuR) binds to the AU-rich element (ARE) in the 3'UTR to stabilize TNF-alpha mRNA. Here, we identified chemical inhibitors of the interaction between HuR and the ARE of TNF-alpha mRNA using RNA electrophoretic mobility gel shift assay (EMSA) and filter binding assay. Of 179 chemicals screened, we identified three with a half-maximal inhibitory concentration (IC(50)) below 10 micrometer. The IC(50) of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 micrometer, respectively, for binding of HuR protein to TNF-alpha mRNA. Quercetin and b-40 did not inhibit binding of tristetraprolin to the ARE of TNF-alpha mRNA. When LPS-treated RAW264.7 cells were treated with quercetin and b-40, we observed decreased stability of TNF-alpha mRNA and decreased levels of secreted TNF-alpha. From these results, we could find inhibitors for the TNF-alpha mRNA stability, which might be used advantageously for both the study for post-transcriptional regulation and the discovery of new anti-inflammation drugs.


Subject(s)
3' Untranslated Regions , Animals , Anti-Inflammatory Agents/pharmacology , Antigens, Surface/metabolism , Antioxidants/pharmacology , Cell Line , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Mice , Protein Binding/drug effects , Quercetin/pharmacology , RNA Stability/drug effects , RNA-Binding Proteins/antagonists & inhibitors , Tumor Necrosis Factor-alpha/biosynthesis
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