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1.
An Acad Bras Cienc ; 92(1): e20190261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401838

RESUMO

Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Citarabina/efeitos adversos , Edema Pulmonar/tratamento farmacológico , Rutina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Masculino , NF-kappa B/análise , Oxidantes/sangue , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , Ratos , Ratos Wistar , Rutina/farmacologia , Fator de Necrose Tumoral alfa/análise
2.
Artigo em Inglês | MEDLINE | ID: mdl-32255737

RESUMO

A new and sensitive electrochemical sensor for rutin determination was developed based on cetyltrimethylammonium chloride (CTAC) functionalized graphene (Gr) and palladium nanoparticles (Pd) (CTAC-Gr-PdNPs) composite. Rutin displayed remarkably increased electrochemical activity on the CTAC-Gr-PdNPs composite modified electrode due to the synergistic effect of the large surface area and electrocatalytic activity of both Gr and Pd nanoparticles, which offers the feasibility for highly sensitive determination of rutin via electrochemistry. Under the optimal experimental conditions, the oxidation peak current of rutin was proportional to its concentration in the range of 2.0 × 10-8-1.0 × 10-6 mol L-1, and the limit of detection (LOD) was 5 nM (S/N = 3). The developed method was successfully applied to determine rutin in pharmaceuticals with satisfactory recoveries, which shows that the fabricated sensor has potential in pharmaceutical analysis.


Assuntos
Técnicas Eletroquímicas/métodos , Grafite/química , Nanopartículas Metálicas/química , Paládio/química , Rutina/análise , Técnicas Eletroquímicas/instrumentação , Eletroquímica , Eletrodos , Desenho de Equipamento , Limite de Detecção , Oxirredução , Rutina/farmacologia
3.
Ecotoxicol Environ Saf ; 192: 110310, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32061987

RESUMO

Smilax brasiliensis (Smilacaceae) is a native Brazilian plant found in the Cerrado biome and commonly used in folk medicine. The aim of this study was to evaluate the allelopathic, cytotoxic, genotoxic, and antigenotoxic potential of extract and fractions of Smilax brasiliensis leaves. Quercetin and rutin isomers were observed in the subfractions. The dichloromethane fraction (1000 µg/mL) decreased lettuce (Lactuca sativa) seed vigor, while and ethyl acetate and hydromethanol fractions (1000 µg/mL) affected the germination, and quercetin and rutin affected the vigor and germination of onion seeds. The extract, fractions, quercetin, and rutin inhibited or promoted lettuce hypocotyl and radicle growth. The extract and fractions inhibited onion hypocotyl growth at all concentrations. With regards to radicle growth, the results were diversified: growth was either inhibited or promoted. Rutin and quercetin inhibited onion hypocotyl and radicle growth at all concentrations. The extract and fractions of Smilax brasiliensis, rutin, and quercetin did not cause cytotoxic effect evaluated by mitotic index. The extract and fractions showed genotoxic effects. Quercetin and rutin did not cause genotoxic effects. On the other hand, the extract and fractions showed antigenotoxic effects at all tested concentrations, where they were able to revert chromosomal abnormalities caused by glyphosate. However, additional studies are required to evaluate the possible use of the S. brasiliensis leaf methanol extract and fractions as natural sources of bioherbicides.


Assuntos
Quercetina/toxicidade , Rutina/toxicidade , Smilax/química , Alelopatia , Citotoxinas/toxicidade , Dano ao DNA/efeitos dos fármacos , Germinação/efeitos dos fármacos , Alface/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Folhas de Planta/química , Quercetina/farmacologia , Rutina/farmacologia , Sementes/efeitos dos fármacos
4.
Biophys Chem ; 258: 106327, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31927393

RESUMO

Serum albumin binds avidly to heme to form heme-serum albumin complex and can protect against the potentially toxic effects of heme. Rutin is a glycoside of the bioflavonoid quercetin with various protective effects due to its antioxidant ability. Clarification of the interaction mechanisms between serum albumin and bioactive components (such as heme and flavonoid) is important to develop effective carriers for encapsulation of heme and suppression of its toxicity. In this study, bindings of bovine serum albumin (BSA) to heme and/or rutin were investigated by experimental and molecular docking techniques. The fluorescence of BSA was quenched by both heme and rutin in static mode (i.e. formation of BSA-monoligand complexes), which was confirmed by Stern-Volmer calculations. Although heme showed higher affinity to BSA than rutin, the interactions of both components with BSA did locate within subdomain IIA (site I). BSA-diligand complexes were successfully formed after the simultaneous addition of heme and rutin. Bioactive rutin in the BSA-diligand complex still kept strong free radical scavenging activity compared to free rutin or BSA-monoligand complex. Hydrogen peroxide (H2O2)-induced heme degradation and free iron release was inhibited upon BSA binding and further decreased in BSA-diligand complexes. Consistently, the cytotoxicity of heme and oxidative stress in endothelial cells was decreased in the BSA-diligand complexes relative to those of heme or BSA-heme complex, where the co-presence of rutin played an important role. These results suggest the possibility and advantage of developing BSA-based carriers for the suppression of heme toxicity in their biomedical applications.


Assuntos
Antioxidantes/farmacologia , Heme/antagonistas & inibidores , Rutina/farmacologia , Soroalbumina Bovina/metabolismo , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Bovinos , Heme/toxicidade , Ligantes , Modelos Moleculares , Rutina/química , Rutina/metabolismo , Soroalbumina Bovina/química
5.
Exp Parasitol ; 209: 107811, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31809705

RESUMO

As gastro-intestinal nematodes (GINs) become increasingly resistant to chemical anthelmintics, and because consumers scrutinize chemical residues in animal products, the use of herbal anthelmintics and in particular, phenolic compounds, has become attractive. Most life stages of GINs cannot be grown in the lab as they are obligatory parasites, which limits our understanding of the effects of phenolic compounds on their parasitic stages of life. We hypothesized that a species phylogenetically close to GINs and grown in vitro, the insect-parasitic nematode Heterorhabditis bacteriophora (Rhabditida; Heterorhabditiade), when fed with Photorhabdus luminescens exposed to plant phenolics, can serve, as proxy for strongyles, in assessing the anthelmintic effects of phenolic compounds. We compared the development of H. bacteriophora infective juveniles (IJ) and the exsheathment rate of L3 larvae of the strongyle Teladorsagia circumcincta and Trichostrongylus colubriformis when exposed to catechin, rutin, chlorogenic and gallic acids, and myricetin. Gallic acid had the highest impact in terms of IJ mortality but the highest impairment of IJ development to adulthood was imposed by myricetin. The studied compounds were not lethal to GINs stricto sensu but we consider that the practical implications of total exsheathment inhibition and mortality on GIN populations are similar. Catechin and rutin had similar effects on rhabditid and strongyles: they imposed ca. 90% lethality of IJs at concentrations higher than 1200 ppm and the remaining live IJs did not develop further, and they also totally inhibited strongyle L3 exsheathment in a dose-response fashion. Gallic acid was 100% lethal to IJs exposed above 300 ppm and chlorogenic acid caused 87% mortality above 1200 ppm, with no development for the surviving IJs but for all lower concentrations, all the IJs developed to adult stages. Likewise, gallic and chlorogenic acids did not affect the exsheatment of GIN L3 larvae. Therefore, a discrepancy between the effects of gallic and chlorogenic acids on the development of rhabditid IJs and exsheathment of GIN L3 larvae was found only when they were exposed to high concentrations. A dose-response of IJ lethality to myricetin was found, with no IJ development between 150 and 2400 ppm; but contrary to the other compounds, myricetin also impaired IJ development of IJs above 10 ppm in a dose-response manner and showed dose-responses in the L3 exsheathment. Apart for the high rates of lethality imposed on IJs by gallic and chlorogenic acids at high concentration, these results suggest that H. bacteriophora fed P. luminescens exposed to phenolics shows potential to serve as model in studies of the anthelmintic effects of phenolics in GIN.


Assuntos
Anti-Helmínticos/farmacologia , Fenóis/farmacologia , Photorhabdus/efeitos dos fármacos , Strongyloidea/efeitos dos fármacos , Animais , Catequina/farmacologia , Ácido Clorogênico/farmacologia , Relação Dose-Resposta a Droga , Fezes/parasitologia , Flavonoides/farmacologia , Ácido Gálico/farmacologia , Cabras , Larva/efeitos dos fármacos , Larva/fisiologia , Rutina/farmacologia , Simbiose
6.
Arch Oral Biol ; 109: 104584, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630006

RESUMO

OBJECTIVES: To investigate whether rutin could protect human periodontal ligament stem cells (hPDLSCs) from TNF-α induced damage to osteogenic differentiation in inflammatory environment and detect the underlying mechanism. MATERIALS AND METHODS: hPDLSCs were identified by flow cytometery. TNF-α was used to stimulate hPDLSCs to establish an inflammation model in vitro. Alkaline phosphatase (ALP) staining, ALP activity test, and Alizarin Red staining were used to detect the changes of osteogenic differentiation ability. The mRNA and protein levels of osteogenic genes were evaluated by RT-PCR and Western Blot. The expression of mTOR was also detected by Western Blot. RESULTS: hPDLSCs were positive to MSCs specific surface markers. The inflammatory environment in vitro could be established by stimulating hPDLSCs with TNF-α (20 ng/mL). TNF-α (20 ng/mL) could decrease the ALP activity and mineralization ability of hPDLSCs and down-regulate the expression of osteogenic genes in inflammatory environment. Moreover, rutin could affect TNF-α (20 ng/mL) induced damage to osteogenic differentiation of hPDLSCs in a dose-dependent manner, 10 µmol/L rutin could significantly reverse the damage caused by TNF-α. In addition, rutin inhibited TNF-α-activated mTOR signal transduction by inhibiting the phosphorylation of mTOR, similar to the effects of rapamycin(a specific mTOR inhibitor). CONCLUSIONS: Rutin could protect hPDLSCs from TNF-α induced damage to osteogenic differentiation in inflammatory environment, and rutin is expected to become a new candidate drug for the treatment of bone defect of periodontitis.


Assuntos
Osteogênese , Ligamento Periodontal/citologia , Rutina/farmacologia , Transdução de Sinais , Células-Tronco/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/efeitos adversos , Fosfatase Alcalina/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Inflamação , Células-Tronco/citologia
7.
Nutrients ; 11(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694226

RESUMO

The combination of ascorbic acid and rutin, often used in oral preparations, due to antioxidant and anti-inflammatory properties, can be used to protect skin cells against the effects of UV radiation from sunlight. Therefore, the aim of this study was to investigate the synergistic effect of rutin and ascorbic acid on the proteomic profile of UVA and UVB irradiated keratinocytes cultured in a three-dimensional (3D) system. Results showed that the combination of rutin and ascorbic acid protects skin cells against UV-induced changes. In particular, alterations were observed in the expression of proteins involved in the antioxidant response, DNA repairing, inflammation, apoptosis, and protein biosynthesis. The combination of rutin and ascorbic acid also showed a stronger cytoprotective effect than when using either compound alone. Significant differences were visible between rutin and ascorbic acid single treatments in the case of protein carboxymethylation/carboxyethylation. Ascorbic acid prevented UV or rutin-induced protein modifications. Therefore, the synergistic effect of rutin and ascorbic acid creates a potentially effective protective system against skin damages caused by UVA and UVB radiation.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Citoproteção/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Rutina/farmacologia , Raios Ultravioleta/efeitos adversos , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Reparo do DNA/efeitos dos fármacos , Humanos , Inflamação , Queratinócitos/efeitos da radiação , Conformação Molecular , Biossíntese de Proteínas/efeitos dos fármacos , Proteômica , Pele/citologia , Luz Solar/efeitos adversos
8.
J Environ Pathol Toxicol Oncol ; 38(2): 153-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679278

RESUMO

Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/induzido quimicamente , Doxorrubicina/farmacologia , Metilnitrosoureia/toxicidade , Substâncias Protetoras/farmacologia , Rutina/farmacologia , Animais , Disfunção Cognitiva/induzido quimicamente , Doxorrubicina/toxicidade , Feminino , Ratos , Ratos Sprague-Dawley
9.
Adv Clin Exp Med ; 28(11): 1537-1543, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31766081

RESUMO

BACKGROUND: Cisplatin, used in cancer treatment, has toxic and apoptotic effects on the peripheral nervous system. Rutin, also known as vitamin P, has antioxidant and antiapoptotic activity. OBJECTIVES: The purpose of this study was to investigate the biochemical and histopathologic efficacy of rutin on neurotoxic and apoptotic effects caused by cisplatin in the peripheral nervous system. MATERIAL AND METHODS: Twenty-four albino Wistar male rats were divided into the following 4 groups: control group (CG), only cisplatin-injected group (CIS), cisplatin and rutin 50 mg/kg (RG-50)-injected group, and cisplatin and rutin 100 mg/kg (RG-100)-injected group. Analyses were performed on sciatic nerve tissue of experimental animals. Analyses of malondialdehyde (MDA), total glutathione (tGSH), glutathione reductase (GSHRd), glutathione-s-transferase (GST), and superoxide dismutase (SOD) were performed. Caspase-3 expression in nerve tissue was also investigated. The analyzed groups were compared with CG. RESULTS: Biochemical investigation shows that there is a statistically significant difference between CG and only CIS and RG-50. Control group and RG-100 were found to be similar. Cisplatin-induced changes were observed in histopathological analysis of the nerve tissue. The RG-100 and CG were found to be similar. The caspase-3 expression in the neural tissue was compared between groups. Control group and CIS were found to be different. Control group and RG-100 were found to be similar. CONCLUSIONS: Antioxidant and antiapoptotic effectiveness of rutin was detected against the toxic effects caused by cisplatin in the peripheral nerve tissue.


Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Cisplatino/efeitos adversos , Tecido Nervoso/efeitos dos fármacos , Rutina/farmacologia , Animais , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Rutina/uso terapêutico , Superóxido Dismutase/metabolismo
10.
Biomed Res Int ; 2019: 6407210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781632

RESUMO

Currently, gastric cancer treatment is mainly based on first-line intervention with oxaliplatin (OXA) after surgical resection, but the application of OXA has been limited due to the toxic side effects caused by the cumulative dose. The toxicity of OXA mainly includes hepatotoxicity, nephrotoxicity, and ototoxicity, and there is an urgent clinical need to find alternatives that are less toxic and more effective. Rutin (RT) is a natural flavonoid with many biological activities. Studies have found that RT inhibits tumor cell growth and enhances their sensitivity toward certain drugs. As the underlying impact of RT on gastric cancer and its molecular mechanism remain poorly understood, we performed a series of experiments to determine whether RT has the effect of treating gastric cancer, and whether it can cooperate with OXA to treat gastric cancer and its related mechanisms. In the present study, we founded that RT suppressed cell viability, inhibited cell proliferation by causing G0/G1 arrest, and induced apoptosis in SGC 7901 cells. And RT can play as an antitumor agent together with OXA. The mechanism of RT-induced apoptosis may be associated with the activation of the p38/Caspase signal pathway. These results demonstrated the potential of RT as a promising therapeutic compound to treat gastric cancer. At the same time, RT can synergize with OXA to reduce the dose of OXA and reduce the toxicity.


Assuntos
Apoptose/efeitos dos fármacos , Oxaliplatina/farmacologia , Rutina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/farmacologia , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimioterapia Combinada , Fase G1/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Neoplasias Gástricas/metabolismo
11.
BMC Plant Biol ; 19(1): 429, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619182

RESUMO

BACKGROUND: Polycomb repressive complex 2 (PRC2) is an epigenetic transcriptional repression system, whose catalytic subunit (ENHANCER OF ZESTE HOMOLOG 2, EZH2 in animals) is responsible for trimethylating histone H3 at lysine 27 (H3K27me3). In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. RESULTS: We show here that the 1,5-bis (3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one compound (RDS 3434), previously reported as an EZH2 inhibitor in human leukemia cells, is active on the Arabidopsis catalytic subunit of PRC2, since treatment with the drug reduces the total amount of H3K27me3 in a dose-dependent fashion. Consistently, we show that the expression level of two PRC2 targets is significantly increased following treatment with the RDS 3434 compound. Finally, we show that impairment of H3K27 trimethylation in Arabidopsis seeds and seedlings affects both seed germination and root growth. CONCLUSIONS: Our results provide a useful tool for the plant community in investigating how PRC2 affects transcriptional control in plant development.


Assuntos
Proteínas de Arabidopsis/antagonistas & inibidores , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Histonas/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteína Potenciadora do Homólogo 2 de Zeste , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica no Desenvolvimento , Lisina/metabolismo , Metilação , Proteínas Repressoras/genética , Rutina/análogos & derivados , Rutina/farmacologia , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo
12.
Int J Mol Med ; 44(6): 2289-2297, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31661130

RESUMO

Cell sheet technology is a novel tissue engineering technology that has been rapidly developed in recent years. As a novel technology, cell sheet technology is expected to become one of the preferred methods for cell transplantation. The present study investigated the biological effects of rutin on the formation of periodontal ligament stem cell (PDLSC) sheets and their resultant osteogenic properties. The results of Cell Counting Kit­8 (CCK­8) assay demonstrated that a concentration of 1x10­6 mol/l rutin promoted the proliferation of PDLSCs more effectively compared with other designed concentrations. Rutin­modified cell sheets could be induced by complete medium supplemented with 20 µg/ml vitamin C (VC) and 1x10­6 mol/l rutin. Rutin­modified cell sheets appeared thicker and more compact compared with the VC­induced PDLSC sheets, demonstrating more layers of cells (3 or 4 layers), which secreted a richer extracellular matrix (ECM). Furthermore, the improved cell sheets exhibited varying degrees of increases in the mRNA and protein expression of collagen type I (COL1), alkaline phosphatase (ALP), runt­related transcription factor 2 (RUNX2) and osteopontin (OPN). Combined treatment with VC and rutin promoted the formation of PDLSC sheets and enhanced the osteogenic differentiation potential of the cell sheets. Therefore, rutin­modified cell sheets of PDLSCs are expected to play an important role in the treatment of periodontal tissue regeneration by stem cells.


Assuntos
Osteogênese/efeitos dos fármacos , Ligamento Periodontal/crescimento & desenvolvimento , Rutina/farmacologia , Células-Tronco/citologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Matriz Extracelular/efeitos dos fármacos , Humanos , Ligamento Periodontal/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Engenharia Tecidual/métodos
13.
Arch Biochem Biophys ; 676: 108157, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31644887

RESUMO

Oxidative stress plays an important role in the pathogenesis of cardiovascular disease. Quercetin, a naturally occurring flavonoid presents in plants and human diet, has been reported to exert antioxidant properties in vivo and in vitro. The upregulation of antioxidant enzyme heme oxygenase-1 (HMOX1) in endothelial cells is considered to be beneficial in cardiovascular disease. In this work, we tested whether quercetin might suppress hydrogen peroxide (H2O2)-induced cell damage in endothelial cells by augmenting this cellular antioxidant defense. It was found that quercetin upregulated HMOX1 expression to protect endothelial cells against oxidative stress, and the protective effects of quercetin on H2O2-induced endothelial cell damage (such as loss of cell viability and reduction of nitric oxide) could be abolished by the specific small-interfering RNA against HMOX1 expression or HMOX1 activity inhibitor. In addition, the activation of ERK/Nrf2 signaling pathway was critical to the upregulation of HMOX1 induced by quercetin. Consistent with its non-effective ability to induce HMOX1, rutin (the glycoside of quercetin) showed less protective effects on H2O2-induced cell damage than quercetin. Therefore, quercetin could attenuate oxidative stress-induced endothelial cell damage at least partly through ERK/Nrf2/HMOX1 pathway. Our results also suggested a novel mechanism for the anti-oxidant property of quercetin and might explain in part the protective cardiovascular effects of diets rich in these compounds.


Assuntos
Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Peróxido de Hidrogênio/toxicidade , Quercetina/farmacologia , Antioxidantes/farmacologia , Células Endoteliais/citologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Rutina/farmacologia , Regulação para Cima/efeitos dos fármacos
14.
Int J Biol Macromol ; 141: 476-483, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473316

RESUMO

Polymer functionalized metal oxide nanocomposites are great interest due to wide range of application, especially in nanomedicine. The present study reports an eco-friendly bio-inspired synthesis of chitosan/copper oxide (CS-CuO) nanocomposite for the first time using rutin. The bio-synthesized CS-CuO nanocomposite was characterized using UV-Visible spectroscopy, FE-SEM, EDS, TEM, XRD and FTIR analyses. FE-SEM and TEM images revealed the synthesized CS-CuO nanocomposite having spherical shaped structure with an average size of 10-30 nm. EDS analysis confirmed the elements present in synthesized CS-CuO nanocomposite. FTIR studies revealed the role of rutin and chitosan for reduction, capping and synthesis of CS-CuO nanocomposite from the precursor copper salt. The XRD analysis revealed monoclinic structure of CS-CuO nanocomposite. Anti-proliferative activity of the CS-CuO nanocomposite was evaluated in human lung cancer cell line A549. Synthesized CS-CuO nanocomposite showed concentration-depended anti-proliferative activity against A549 cancer cells and their IC50 value was found to be 20 ±â€¯0.50 µg/mL. Furthermore, synthesized nanocomposite induce apoptosis in treated A549 cancer cells assayed by AO/EtBr fluorescent staining method. In conclusion, the synthesized CS-CuO nanocomposite using rutin can be used as a potential anticancer agent in biomedical and clinical sectors.


Assuntos
Antineoplásicos , Quitosana , Cobre , Neoplasias Pulmonares , Nanocompostos , Rutina , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Quitosana/química , Quitosana/farmacologia , Cobre/química , Cobre/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Nanocompostos/química , Nanocompostos/uso terapêutico , Rutina/química , Rutina/farmacologia
15.
Food Chem Toxicol ; 133: 110749, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377139

RESUMO

A new protocol to obtain egg yolk phospholipids in ethanol is presented. Rutin-phospholipids nanoliposomes were prepared and characterized. The procedure takes advantage of the different solubility of egg yolk lipids in ethanol and acetone at low temperature, to efficiently obtain a phospholipid-rich fraction of high purity degree. The phospholipid content in the final fraction is 208.65 ± 26.46 µmol/g fresh egg yolk (16%), accounting for ca. 96% of the extract's dry weight. The phospholipid-rich fraction contains cholesterol (0.069-0.082 cholesterol/phospholipid molar ratio), and vestigial amounts of lutein and zeaxanthin (89.24 ± 9.76 and 14.9 ± 2.16 ng/g of fresh egg yolk, respectively). Saturated fatty acids dominate the extracted phospholipids (50% of egg's total yolk phospholipids), the levels of monounsaturated ranging from 20 to 25%, and polyunsaturated up to 35%. Rutin-liposomes, prepared with phospholipid-rich fraction, presented mean diameter <140 nm, negative surface charge (Zeta potential ~ -13 mV), and entrapment efficiency of rutin up to 87%. In human neuroblastoma cell line SH-SY5Y, rutin-liposomes (lipid 25 µM + rutin 16.7 µM) attenuated glutamate-induced cytotoxicity, in part by reducing the formation of intracellular reactive species, pointing to their potential application as new functional neuroprotective agents.


Assuntos
Portadores de Fármacos/química , Gema de Ovo/química , Lipossomos/química , Fármacos Neuroprotetores/farmacologia , Fosfolipídeos/química , Rutina/farmacologia , Acetona/química , Animais , Carotenoides/análise , Carotenoides/isolamento & purificação , Linhagem Celular Tumoral , Colesterol/análise , Colesterol/isolamento & purificação , Etanol/química , Humanos , Extração Líquido-Líquido/métodos , Fosfolipídeos/análise , Fosfolipídeos/isolamento & purificação
16.
Molecules ; 24(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461832

RESUMO

Pomegranate peel is a natural source of phenolics, claimed to possess healing properties, among which are antioxidant and antidiabetic. In the present study, an ethyl acetate extract, obtained by Soxhlet from the peel of Dente di Cavallo DC2 pomegranate (PGE) and characterized to contain 4% w/w of ellagic acid, has been evaluated for its hypoglycemic, antiglycation, and antioxidative cytoprotective properties, in order to provide possible evidence for future nutraceutical applications. The α-amylase and α-glucosidase enzyme inhibition, interference with advanced glycation end-products (AGE) formation, and metal chelating abilities were studied. Moreover, the possible antioxidant cytoprotective properties of PGE under hyperglycemic conditions were assayed. Phenolic profile of the extract was characterized by integrated chromatographic and spectrophotometric methods. PGE resulted able to strongly inhibit the tested enzymes, especially α-glucosidase, and exerted chelating and antiglycation properties. Also, it counteracted the intracellular oxidative stress under hyperglycemic conditions, by reducing the levels of reactive oxygen species and total glutathione. Among the identified phenolics, rutin was the most abundant flavonoid (about 4 % w/w). Present results suggest PGE to be a possible remedy for hyperglycemia management and encourage further studies to exploit its promising properties.


Assuntos
Antioxidantes/química , Hipoglicemiantes/química , Fenóis/química , Romã (Fruta)/química , Antioxidantes/farmacologia , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Glutationa/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rutina/química , Rutina/farmacologia , alfa-Amilases/antagonistas & inibidores
17.
Artigo em Inglês | MEDLINE | ID: mdl-31454703

RESUMO

This research aimed to assess the influence of dietary addition of rutin on inflammation, apoptosis and antioxidative responses in muscle of silver catfish (Rhamdia quelen) challenged with Aeromonas hydrophila (A. hydrophila). Fish were split into four groups as follows: control, 0.15% rutin, A. hydrophila, 0.15% rutin + A. hydrophila. After 2 weeks of feeding with standard or rutin diets, fish were challenged or not with A. hydrophila for 1 week. Rutin-added diet abrogates A. hydrophila induced-hemorrhage and inflammatory infiltration. It decreases A. hydrophila induced-apoptosis through decreasing the ratio of Bax to Bcl-2 and increasing phospho-Akt to Akt ratio. It diminishes the A. hydrophila induced-rise in nitric oxide and superoxide anion levels and reestablishes superoxide dismutase activity as well. Although such diet is unable to recover the levels of reduced glutathione (GSH), cysteine and glutamate cysteine ligase, which are depleted as a result of A. hydrophila infection, it diminishes the oxidized glutathione (GSSG) content, thus decreasing GSSG to GSH ratio. It increases the levels of cysteine residues of proteins and diminishes those of thiol-protein mixed disulfides, which were changed after A. hydrophila challenge. Finally, it reduces A. hydrophila induced-lipid peroxidation, markedly elevates ascorbic acid and thus reestablishes total antioxidant capacity, whose levels were decreased after A. hydrophila challenge. In conclusion, the dietary addition of rutin at 0.15% impairs A. hydrophila-induced inflammatory response, inhibits A. hydrophila-induced apoptosis and promotes cell survival. It also reduces the A. hydrophila-induced oxidative stress and stimulates the antioxidative responses in muscle of A. hydrophila-infected silver catfish.


Assuntos
Peixes-Gato/imunologia , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas , Músculos/metabolismo , Rutina/farmacologia , Aeromonas hydrophila , Ração Animal , Animais , Antioxidantes/farmacologia , Apoptose , Suplementos Nutricionais , Infecções por Bactérias Gram-Negativas/metabolismo , Infecções por Bactérias Gram-Negativas/veterinária , Estresse Oxidativo , Substâncias Protetoras/farmacologia
18.
Molecules ; 24(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31454945

RESUMO

Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is rich in functional compounds such as rutin, quercetin, d-chiro-inositol, dietary fiber, and essential amino acids. Electric field (EF) treatment before sprout germination results in physiological and chemical changes, and some alterations might lead to positive applications in plant seeds. MTT assay showed that the effect of total flavonoids on human gastric cancer cell line MGC80-3 was significantly changed after EF treatment for different germination days (3-7 days). Among them, the total flavonoids of tartary buckwheat (BWTF) on the third day had the most obvious inhibitory effect on MGC80-3 (p < 0.01). In addition, flow cytometry evidenced that different ratios of quercetin and rutin had effects on the proliferation of MGC80-3. The same content of quercetin and rutin had the best effect, reaching 6.18 ± 0.82%. The anti-cancer mechanism was mainly promoted by promoting the expression of apoptotic proteins. The expression of Bax/Bcl-2 and caspase-8 in MGC80-3 cells was mediated by BWTFs. This study has good research value for improving the biological and economic value of tartary buckwheat.


Assuntos
Fagopyrum/fisiologia , Quercetina/farmacologia , Rutina/farmacologia , Neoplasias Gástricas/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Fagopyrum/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Germinação , Humanos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quercetina/isolamento & purificação , Rutina/isolamento & purificação , Neoplasias Gástricas/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo
19.
J Trace Elem Med Biol ; 56: 60-68, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442956

RESUMO

OBJECTIVE: Mercury is a global environmental pollutant and is responsible for several organ pathophysiology including oxidative stress-induced liver disorders. Therefore, the present study was conducted to evaluate the potential ameliorative effects of rutin on mercury chloride (HgCl2)-induced hepatotoxicity in adult male rats. METHODS: HgCl2 was intraperitoneally injected at a dose of 1.23 mg/kg body weight for 7 days alone or in combination with the orally rutin (50 and 100 mg/kg body weight). RESULTS: Rutin treatment significantly improved liver function tests [alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], and increased activities of antioxidant defense system [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and glutathione (GSH) content. The histological alterations and epidermal growth factor receptor (EGFR) expression in the HgCl2-induced liver tissues were decreased by administration of rutin. Furthermore, rutin reversed the changes in levels of apoptosis and inflammation related proteins involving p53, Bcl-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cytochrome c, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma-3(Bcl-3) and interleukin-1ß (IL-1ß), and inhibited p38α mitogen-activated protein kinase (MAPK) and cysteine aspartate specific protease-3 (caspase-3) activations. CONCLUSION: The data of the present study suggest that rutin effectively suppress HgCl2-induced hepatotoxicity by ameliorating oxidative stress, inflammation and apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Inflamação/patologia , Fígado/patologia , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Rutina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Biomarcadores/sangue , Receptores ErbB/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/lesões , Masculino , Ratos Sprague-Dawley , Rutina/química , Rutina/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Environ Sci Pollut Res Int ; 26(28): 29074-29084, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392614

RESUMO

The present study aimed to examine the ameliorative effects of morin and rutin on the reproductive toxicity induced by titanium dioxide nanoparticles (TiO2NPs) in male rats. A total of seventy adult male Sprague-Dawley rats were randomly divided into seven groups, each comprising ten rats. Nanoreprotoxicity was induced by treating rats with TiO2NPs at a dosage of 300 mg/kg body weight for 30 days. Morin (30 mg/kg body weight) and rutin (100 mg/kg body weight) were co-administered with or without TiO2NPs to rats either individually or combined. Only distilled water was administered to the control group. The results showed that TiO2NPs enhanced oxidative stress, indicated by reduced levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in testicular tissues, and increased levels of the lipid peroxidation marker malondialdehyde (MDA). TiO2NPs significantly reduced the levels of sex hormones (testosterone, FSH, and LH), reduced sperm motility, viability, and sperm cell count, and increased sperm abnormalities, in addition to damaging the testicular histological architecture. TiO2NPs resulted in the downregulation of 17ß-HSD and the upregulation of proapoptotic gene (Bax) transcripts in the testicular tissues. Conversely, morin and/or rutin had a protective effect on testicular tissue. They effectively counteracted TiO2NP-induced oxidative damage and morphological injury in the testis by conserving the endogenous antioxidant mechanisms and scavenging free radicals. Thus, we suggest that morin and rutin could be used to alleviate the toxicity and oxidative damage associated with TiO2NP intake.


Assuntos
Antioxidantes/farmacologia , Flavonoides/farmacologia , Nanopartículas/toxicidade , Rutina/farmacologia , Titânio/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testosterona/metabolismo
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