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1.
Braz J Biol ; 83: e247165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468525

RESUMO

Now a day's multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.


Assuntos
Antibacterianos , Ácido Ascórbico , Antibacterianos/farmacologia , Ácido Ascórbico/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Testes de Sensibilidade Microbiana
2.
Molecules ; 26(15)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34361837

RESUMO

Allergy is an excessive immune response to a specific antigen. Type I allergies, such as hay fever and food allergies, have increased significantly in recent years and have become a worldwide problem. We previously reported that an ascorbic acid derivative having palmitoyl and glucosyl groups, 2-O-α-d-glucopyranosyl-6-O-hexadecanoyl-l-ascorbic acid (6-sPalm-AA-2G), showed inhibitory effects on degranulation in vitro and on the passive cutaneous anaphylaxis (PCA) reaction in mice. In this study, several palmitoyl derivatives of ascorbic acid were synthesized and a structure-activity relationship study was performed to discover more potent ascorbic acid derivatives with degranulation inhibitory activity. 6-Deoxy-2-O-methyl-6-(N-hexadecanoyl)amino-l-ascorbic acid (2-Me-6-N-Palm-AA), in which a methyl group was introduced into the hydroxyl group at the C-2 position of ascorbic acid and in which the hydroxyl group at the C-6 position was substituted with an N-palmitoyl group, exhibited much higher inhibitory activity for degranulation in vitro than did 6-sPalm-AA-2G. 2-Me-6-N-Palm-AA strongly inhibit the PCA reaction in mice at lower doses than those of 6-sPalm-AA-2G. These findings suggest that 2-Me-6-N-Palm-AA may be a promising therapeutic candidate for allergic diseases.


Assuntos
Antialérgicos , Ácido Ascórbico , Degranulação Celular/efeitos dos fármacos , Hipersensibilidade/tratamento farmacológico , Anafilaxia Cutânea Passiva , Animais , Antialérgicos/síntese química , Antialérgicos/química , Antialérgicos/farmacologia , Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/síntese química , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Modelos Animais de Doenças , Camundongos
3.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445461

RESUMO

Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degradation, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antioxidant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of MMP1 and MMP7 expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.


Assuntos
Antioxidantes , Ácido Ascórbico , Colágeno/biossíntese , Fibroblastos/metabolismo , Guaiacol/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Ácido Ascórbico/farmacocinética , Ácido Ascórbico/farmacologia , Linhagem Celular , Guaiacol/farmacocinética , Guaiacol/farmacologia , Humanos
4.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361729

RESUMO

Tyrosinase (TYR) is a type III copper oxidase present in fungi, plants and animals. The inhibitor of human TYR plays a vital role in pharmaceutical and cosmetic fields by preventing synthesis of melanin in the skin. To search for an effective TYR inhibitor from various plant extracts, a kinetic study of TYR inhibition was performed with mushroom TYR. Among Panax ginseng, Alpinia galanga, Vitis vinifera and Moringa oleifera, the extracts of V. vinifera seed, A. galanga rhizome and M. oleifera leaf reversibly inhibited TYR diphenolase activity with IC50 values of 94.8 ± 0.2 µg/mL, 105.4 ± 0.2 µg/mL and 121.3 ± 0.4 µg/mL, respectively. Under the same conditions, the IC50 values of the representative TYR inhibitors of ascorbic acid and kojic acid were found at 235.7 ± 1.0 and 192.3 ± 0.4 µg/mL, respectively. An inhibition kinetics study demonstrated mixed-type inhibition of TYR diphenolase by A. galanga and V. vinifera, whereas a rare uncompetitive inhibition pattern was found from M. oleifera with an inhibition constant of Kii 73 µg/mL. Phytochemical investigation by HPLC-MS proposed luteolin as a specific TYR diphenolase ES complex inhibitor, which was confirmed by the inhibition kinetics of luteolin. The results clearly showed that studying TYR inhibition kinetics with plant extract mixtures can be utilized for the screening of specific TYR inhibitors.


Assuntos
Inibidores Enzimáticos/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Luteolina/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Moringa oleifera/química , Agaricales/química , Agaricales/enzimologia , Alpinia/química , Ácido Ascórbico/química , Ácido Ascórbico/isolamento & purificação , Ácido Ascórbico/farmacologia , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Proteínas Fúngicas/isolamento & purificação , Ensaios de Triagem em Larga Escala , Concentração Inibidora 50 , Cinética , Luteolina/química , Luteolina/isolamento & purificação , Monofenol Mono-Oxigenase/isolamento & purificação , Panax/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pironas/química , Pironas/isolamento & purificação , Pironas/farmacologia , Rizoma/química , Sementes/química , Vitis/química
5.
Nat Biomed Eng ; 5(8): 880-896, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34426676

RESUMO

Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types using the microRNA mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells to the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.


Assuntos
Células Endoteliais/transplante , Coração/fisiologia , Infarto do Miocárdio/terapia , Miócitos de Músculo Liso/transplante , Regeneração , Animais , Ácido Ascórbico/farmacologia , Proteína Morfogenética Óssea 4/farmacologia , Reprogramação Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Junções Comunicantes/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Neovascularização Fisiológica , Transcriptoma
6.
Am J Hum Genet ; 108(9): 1710-1724, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34450031

RESUMO

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants in COPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures, and developmental delay of variable severity. Electron microscopy of COPB2-deficient subjects' fibroblasts showed dilated endoplasmic reticulum (ER) with granular material, prominent rough ER, and vacuoles, consistent with an intracellular trafficking defect. We studied the effect of COPB2 deficiency on collagen trafficking because of the critical role of collagen secretion in bone biology. COPB2 siRNA-treated fibroblasts showed delayed collagen secretion with retention of type I collagen in the ER and Golgi and altered distribution of Golgi markers. copb2-null zebrafish embryos showed retention of type II collagen, disorganization of the ER and Golgi, and early larval lethality. Copb2+/- mice exhibited low bone mass, and consistent with the findings in human cells and zebrafish, studies in Copb2+/- mouse fibroblasts suggest ER stress and a Golgi defect. Interestingly, ascorbic acid treatment partially rescued the zebrafish developmental phenotype and the cellular phenotype in Copb2+/- mouse fibroblasts. This work identifies a form of coatopathy due to COPB2 haploinsufficiency, explores a potential therapeutic approach for this disorder, and highlights the role of the COPI complex as a regulator of skeletal homeostasis.


Assuntos
Osso e Ossos/metabolismo , Complexo I de Proteína do Envoltório/genética , Proteína Coatomer/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Osteoporose/genética , Animais , Ácido Ascórbico/farmacologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Pré-Escolar , Complexo I de Proteína do Envoltório/deficiência , Proteína Coatomer/química , Proteína Coatomer/deficiência , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/metabolismo , Deficiências do Desenvolvimento/patologia , Embrião não Mamífero , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação da Expressão Gênica no Desenvolvimento , Complexo de Golgi , Haploinsuficiência , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/metabolismo , Deficiência Intelectual/patologia , Masculino , Camundongos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Índice de Gravidade de Doença , Peixe-Zebra
7.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371879

RESUMO

Sepsis is an extremely complex clinical syndrome, usually involving an excessive inflammatory response including an overshooting cytokine release that damages tissue and organs of the patient. Due to the severity of this condition, it is estimated that over 11 million people die from sepsis each year. Despite intensive research in the field, there is still no specific therapy for sepsis. Many sepsis patients show a marked deficiency of vitamin C. 9 out of 10 sepsis patients have a hypovitaminosis C, and every third patient even shows a clinical deficiency in the scurvy range. In addition, low vitamin C levels of intensive care sepsis patients correlate with a higher need for vasopressors, higher Sequential Organ Failure Assessment (SOFA) scores, and increased mortality. Based on this observation and the conducted clinical trials using vitamin C as sepsis therapy in intensive care patients, the aim of the present ex vivo study was to evaluate the effects of high-dose vitamin C alone and in a triple combination supplemented with vitamin B1 (thiamine) and hydrocortisone on the lipopolysaccharide (LPS)-induced cytokine response in peripheral blood mononuclear cells (PBMCs) from healthy human donors. We found that all corticosteroid combinations strongly reduced the cytokine response on RNA- and protein levels, while high-dose vitamin C alone significantly diminished the PBMC mediated secretion of the cytokines interleukin (IL)-10, IL-23, and monocyte chemo-attractant protein (MCP-1), which mediate the inflammatory response. However, vitamin C showed no enhancing effect on the secretion of further cytokines studied. This data provides important insights into the possible immunomodulatory function of vitamin C in an ex vivo setting of human PBMCs and the modulation of their cytokine profile in the context of sepsis. Since vitamin C is a vital micronutrient, the restoration of physiologically adequate concentrations should be integrated into routine sepsis therapy, and the therapeutic effects of supraphysiological concentrations of vitamin C in sepsis patients should be further investigated in clinical trials.


Assuntos
Anti-Inflamatórios/farmacologia , Ácido Ascórbico/farmacologia , Hidrocortisona/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Sepse/tratamento farmacológico , Tiamina/farmacologia , Adulto , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Sepse/metabolismo , Adulto Jovem
8.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203225

RESUMO

Colorectal cancer is the second most frequently diagnosed cancer worldwide. Conventional diagnostics methods of colorectal cancer can detect it at an advanced stage. Spectroscopic methods, including Raman spectroscopy and imaging, are becoming more and more popular in medical applications, and allow fast, precise, and unambiguous differentiation of healthy and cancerous samples. The most important advantage of Raman spectroscopy is the ability to identify biomarkers that help in the differentiation of healthy and cancerous cells based on biochemistry of sample and spectra typical for lipids, proteins, and DNA. The aim of the study was to evaluate the biochemical and structural features of human colon cell lines based on Raman spectroscopy and imaging: normal cells CCD-18 Co, normal cells CCD-18 Co under oxidative stress conditions, and normal cells CCD-18 Co at first treated by using tert-Butyl hydroperoxide and then supplemented by vitamin C in high concentration to show the protective role of vitamin C in micromolar concentrations against ROS (Reactive Oxygen Species). Raman data obtained for normal cells injured by ROS were compared with spectra typical for cancerous cells. Statistically assisted analysis has shown that normal ROS-injured and cancerous human colon cells can be distinguished based on their unique vibrational properties. The research carried out proves that label-free Raman spectroscopy may play an important role in clinical diagnostics differentiation of normal and cancerous colon cells and may be a source of intraoperative information supporting histopathological analysis.


Assuntos
Ácido Ascórbico/farmacologia , Neoplasias do Colo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Humanos , Estresse Oxidativo/efeitos dos fármacos , Análise Espectral Raman
9.
Fish Physiol Biochem ; 47(4): 1271-1282, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34228252

RESUMO

In this study, the mechanism that vitamin C (VC) regulates the production of reactive oxygen species (ROS) through Wnt10b signaling was investigated in the gill of zebrafish (Danio rerio). The results showed that 0.5 and 1.0 g/kg VC diets induced the gene expression of Wnt10b, ß-catenin, SOD, CAT, and GSH-PX in gill. In addition, VC decreased the levels of H2O2, O2·- and ·OH, whereas the activities of SOD, CAT, and GSH-PX were increased by VC in the gill of zebrafish. To evaluate the role of Wnt10b in regulating oxidative stress, Wnt10b RNA was further interfered and the gene expression and activities of antioxidant enzymes were detected in gill. The result of Wnt10b RNA interference showed that Wnt10b signaling played a key role in regulating the gene expression of SOD, CAT, and GSH-PX. In all, VC may regulate the production of ROS through Wnt10b signaling in the gill of zebrafish (Danio rerio).


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Brânquias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Vitaminas/farmacologia , Animais , Proteínas de Peixes/genética , Expressão Gênica/efeitos dos fármacos , Brânquias/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Masculino , Estresse Oxidativo , Oxirredutases/genética , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/genética , Peixe-Zebra , beta Catenina/genética
10.
Nutrients ; 13(7)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206952

RESUMO

Age-related neurodegenerative disorders are an increasing public health problem. Oxidative stress is one of the major causes. Medicinal plant-based functional foods can be effective for these diseases. The aim of this work is to investigate the neuroprotective role of methanol extracts of Moringa oleifera leaf powder on antioxidant/oxidant imbalance and mitochondrial regulation in a H2O2-induced oxidative stress model in human neuroblastoma cells. On nutritional analysis, results showed that moringa contained 28.50% carbohydrates, 25.02% proteins, 10.42% fat, 11.83% dietary fiber, 1.108 mg ß-carotene, 326.4 µg/100 g vitamin B1 and 15.2 mg/100 g vitamin C. In-vitro assays revealed that moringa methanol extracts had more phenolic content and higher antioxidant activity than acetone extracts. Moreover, pretreatments with methanol extracts showed a protective effect against H2O2-induced oxidative damage through increasing cell viability and reducing free radicals. Furthermore, the extract decreased lipid peroxidation and enhanced glutathione levels and antioxidant enzyme activity. Finally, moringa also prevented mitochondrial dysfunction by regulating calcium levels and increasing mitochondrial membrane potential. The most active concentration was 25 µg/mL. In summary, the nutritional and functional properties of Moringa oleifera as a neuroprotective agent could be beneficial to protect against oxidative stress and provide necessary nutrients for a healthy diet.


Assuntos
Antioxidantes/farmacologia , Mitocôndrias/metabolismo , Moringa oleifera/química , Fármacos Neuroprotetores/farmacologia , Valor Nutritivo , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ácido Ascórbico/farmacologia , Radicais Livres , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos , Metanol , Mitocôndrias/efeitos dos fármacos , Moringa , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Pós , beta Caroteno/metabolismo
11.
Nutrients ; 13(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200192

RESUMO

Vitamin E was identified as a lipophilic compound essential to maintain rat pregnancy. Low vitamin E intake during early pregnancy associates with congenital malformations and embryonic loss in animals and with miscarriage and intrauterine growth restriction in humans. Vitamin E protects cell membranes from lipoperoxidation and exerts non-antioxidant activities. Its function can be restored by vitamin C; thus, intake and circulating levels of both micronutrients are frequently analyzed together. Although substantial vitamin E inadequacy was reported worldwide, its consumption in Latin America (LatAm) is mostly unknown. Using data from the Latin American Study of Nutrition and Health (Estudio Latinoamericano de Nutrición y Salud, ELANS), we evaluated vitamin E and C intake in women of reproductive age (WRA) from eight LatAm countries and identified their main food sources. Two non-consecutive 24-h dietary recalls in 3704 women aged from 15 to 49 years and living in urban locations showed low average intake of vitamin E (7.9 mg/day vs. estimated average requirement (EAR) of 12 mg/day) and adequate overall vitamin C consumption (95.5 mg/day vs. EAR of 60 mg/day). The mean regional inadequacy was 89.6% for vitamin E and 36.3% for vitamin C. The primary food sources of vitamin E were fats and oils, as well as vegetables. Vitamin C intake was explained mainly by the consumption of fruit juices, fruits, and vegetables. Combined deficient intake of both vitamins was observed in 33.7% of LatAm women. Although the implications of low antioxidant vitamins' consumption in WRA are still unclear, the combined deficient intake of both vitamins observed in one-third of ELANS participants underscores the need for further research on this topic.


Assuntos
Ácido Ascórbico/farmacologia , Saúde , Estado Nutricional , Reprodução , Vitamina E/farmacologia , Adolescente , Adulto , Fatores Etários , Comportamento Alimentar , Feminino , Alimentos , Humanos , América Latina , Pessoa de Meia-Idade , Adulto Jovem
12.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205369

RESUMO

The benefits of natural honeybee products (e.g., honey, royal jelly, beeswax, propolis, beevenom and pollen) to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells and stimulation of the immune system. The type of plants in the geographical area, climatic conditions and production method have a significantly influence on the nutritional quality of honey. However, this variability can influence consumer liking by the sensory attributes of the product. The aim of this work was to compare the most popular honeys from Poland in terms of nutritional value, organoleptic properties and antioxidant activity. In the study, five varieties of honey (honeydew, forest, buckwheat, linden and dandelion) from conventional and organic production methods were tested. The nutritional characteristics of honey samples included acidity, content of water, sugars, vitamin C, HMF and phenolics (total and flavonoids), while honey color, taste, aroma and consistency were investigated in the organoleptic characteristics. The antioxidant activity was determined in water- and ethanol-soluble honey extracts using DPPH and ORAC tests. The results showed that organoleptic and nutritional characteristics of popular Polish honeys differ significantly in relation to plant source and production method. The significant effect of honey variety on the content of HMF, saccharose and phenolics, as well as acidity and antioxidant capacity were noted. The impact of variety and variety × production method interaction was significant in the case of the content of vitamin C, glucose and fructose. A visible difference of buckwheat and forest honeys from other samples was observed. The highest content of total phenolics with antioxidant activity based on the SET mechanism was found in buckwheat honeys, while forest honeys were richer in flavonoids.


Assuntos
Antioxidantes/farmacologia , Abelhas/metabolismo , Mel/análise , Nutrientes/farmacologia , Animais , Ácido Ascórbico/farmacologia , Etanol/química , Fagopyrum , Feminino , Flavonoides/farmacologia , Frutose/farmacologia , Glucose/farmacologia , Sistema Imunitário/efeitos dos fármacos , Masculino , Fenóis/farmacologia , Polônia , Água/química
13.
Int J Mol Sci ; 22(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299372

RESUMO

Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed under laboratory-specific culture conditions with different culture media. However, the effect of different media conditions on bone formation has not been investigated. Here, we aimed to evaluate the osteogenesis of MC3T3-E1 cells, one of the most commonly used osteoblast-like cell lines for osteogenesis evaluation, and assayed cell proliferation, alkaline phosphatase activity, expression of osteoblast markers, and calcification under varying culture media conditions. Furthermore, the various media conditions were tested in uncoated plates and plates coated with collagen type I and poly-L-lysine, highly biocompatible molecules commonly used as pseudobiomaterials. We found that the type of base medium, the presence or absence of vitamin C, and the freshness of the medium may affect biomaterial regeneration. We posit that an in vitro model that recapitulates in vivo bone formation should be established before evaluating biomaterials.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Osteogênese/efeitos dos fármacos , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Ácido Ascórbico/farmacologia , Materiais Biocompatíveis/farmacologia , Biomarcadores/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo
14.
Am J Physiol Regul Integr Comp Physiol ; 321(1): R49-R61, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075811

RESUMO

Posttraumatic stress disorder (PTSD) has been associated with an increase in risk of cardiovascular disease (CVD). The goal of this study was to determine if peripheral vascular dysfunction, a precursor to CVD, was present in young adults with PTSD, and if an acute antioxidant (AO) supplementation could modify this potential PTSD-induced vascular dysfunction. Thirteen individuals with PTSD were recruited for this investigation and were compared with 35 age- and sex-matched controls (CTRL). The PTSD group participated in two visits, consuming either a placebo (PTSD-PL) or antioxidants (PTSD-AO; vitamins C and E; α-lipoic acid) before their visits, whereas the CTRL subjects only participated in one visit. Upper and lower limb vascular functions were assessed via flow-mediated dilation and passive leg movement technique. Heart rate variability was utilized to assess autonomic nervous system modulation. The PTSD-PL condition, when compared with the CTRL group, reported lower arm and leg microvascular function as well as sympathetic nervous system (SNS) predominance. After acute AO supplementation, arm, but not leg, microvascular function was improved and SNS predominance was lowered to which the prior difference between PTSD group and CTRL was no longer significant. Young individuals with PTSD demonstrated lower arm and leg microvascular function as well as greater SNS predominance when compared with age- and sex-matched controls. Furthermore, this lower vascular/autonomic function was augmented by an acute AO supplementation to the level of the healthy controls, potentially implicating oxidative stress as a contributor to this blunted vascular/autonomic function.


Assuntos
Ácido Ascórbico/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Ácido Tióctico/farmacologia , Vitamina E/farmacologia , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Ácido Ascórbico/administração & dosagem , Pressão Sanguínea , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Masculino , Ácido Tióctico/administração & dosagem , Vitamina E/administração & dosagem , Adulto Jovem
15.
J Dermatol Sci ; 103(1): 41-48, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34147320

RESUMO

BACKGROUND: Phagocytosis is an essential process that maintains cellular homeostasis. In the epidermis, the phagocytosis of melanosomes into keratinocytes is important to protect their DNA against damage from ultraviolet B (UVB) radiation. Furthermore, it is considered that UVB activates the phagocytosis by keratinocytes but the detailed mechanism involved is not fully understood. OBJECTIVE: To clarify the mechanism of UVB-enhanced phagocytosis in keratinocytes, we investigated the relationship between the phagocytic ability of keratinocytes and the cell cycle stage of keratinocytes. METHODS: The phagocytic ability of keratinocytes was evaluated using the incorporation of fluorescent beads after exposure to UVB or oxidative stress. S-phase was evaluated by BrdU incorporation and immunostaining of cyclin D1. Intracellular calcium levels of keratinocytes were measured using the probe Fluo-4AM. RESULTS: The phagocytosis of fluorescent beads into keratinocytes was enhanced by UVB and also by oxidative stress. We found that keratinocytes exposed to UVB or oxidative stress were at S-phase of the cell cycle. Furthermore, keratinocytes synchronized to S-phase showed a higher phagocytic ability according to the increased intracellular ROS level. The UVB-enhanced phagocytosis and entrance into S-phase of keratinocytes was abolished by ascorbic acid, a typical antioxidant. Keratinocytes synchronized to S-phase and exposed to UVB or oxidative stress had increased levels of intracellular calcium and their enhanced phagocytic abilities were diminished by the calcium ion chelator BAPTA-AM. CONCLUSION: Taken together, intracellular oxidative stress induced by intracellular calcium influx mediates the UVB-enhanced phagocytic ability of keratinocytes accumulating at S-phase of the cell cycle.


Assuntos
Cálcio/metabolismo , Queratinócitos/efeitos da radiação , Fagocitose/efeitos da radiação , Pontos de Checagem da Fase S do Ciclo Celular/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Linhagem Celular , Quelantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Melaninas/biossíntese , Melanossomas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Estresse Oxidativo/efeitos da radiação , Fagocitose/efeitos dos fármacos , Fagocitose/genética , Espécies Reativas de Oxigênio/metabolismo
16.
Biomed Pharmacother ; 141: 111823, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147902

RESUMO

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.


Assuntos
Ácido Ascórbico/química , Ácido Ascórbico/uso terapêutico , Sulfato de Magnésio/química , Sulfato de Magnésio/uso terapêutico , Niacinamida/química , Niacinamida/uso terapêutico , Ácido Pantotênico/química , Ácido Pantotênico/uso terapêutico , Piridoxina/química , Piridoxina/uso terapêutico , Riboflavina/química , Riboflavina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Tiamina/química , Tiamina/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Cães , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Composição de Medicamentos , Feminino , Humanos , Lipopolissacarídeos/toxicidade , Sulfato de Magnésio/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Niacinamida/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ácido Pantotênico/farmacologia , Piridoxina/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Riboflavina/farmacologia , Sepse/patologia , Superóxido Dismutase/metabolismo , Tiamina/farmacologia
17.
J Food Sci ; 86(7): 3265-3276, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34160066

RESUMO

Hyperuricemia contributes to chronic kidney disease development. However, it has been historically viewed with limited research interest. In this study, we mimicked the development of hyperuricemic nephropathy by using a potassium oxonate-induced hyperuricemia rat model. We found that administering vitamin C at 10 mg/kg/day effectively ameliorated hyperuricemic nephropathy. Compared to the control group, rats with hyperuricemia had significantly increased serum uric acid level, xanthine oxidase activity, and urine microalbumin level, by 5-fold, 1.5-fold, and 4-fold, respectively. At the same time, vitamin C supplementation reverted these values by 20% for serum uric acid level and xanthine oxidase activity and 50% for microalbumin level. Vitamin C also alleviated renal pathology and decreased the expression of pro-inflammatory and pro-fibrotic markers. A further mechanistic study suggested that vitamin C might attenuate hyperuricemic nephropathy in renal tubular epithelial cells induced by monosodium urate (MSU) crystal, at least in part, by directly inhibiting IL-6/JAK2/STAT3 signaling pathway. Meanwhile, in macrophages, vitamin C inhibited the expression of TGF-ß, and reduced ROS level induced by MSU by about 35%. In short, our results suggest that vitamin C supplementation delay the progression of hyperuricemic nephropathy.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Fibrose/prevenção & controle , Hiperuricemia/tratamento farmacológico , Inflamação/prevenção & controle , Nefropatias/tratamento farmacológico , Animais , Fibrose/etiologia , Fibrose/patologia , Hiperuricemia/induzido quimicamente , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Inflamação/etiologia , Inflamação/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Ácido Oxônico/toxicidade , Ratos , Ratos Sprague-Dawley
18.
Acta Biomater ; 130: 223-233, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34087444

RESUMO

Epigallocatechin gallate (EGCG) is a potential therapeutic agent for treatment of atopic dermatitis (AD) due to its antioxidant and anti-inflammatory activities. However, inherent instability of EGCG greatly limits its bioavailability and clinical efficacy. In this study, we developed a poly-γ-glutamate (γ-PGA)-based microneedle (MN) formulation capable of maintaining EGCG's stability and efficiently delivering EGCG into the skin to ameliorate AD symptoms. The γ-PGA MN can not only protect EGCG from oxidation, but also serve as an immunomodulator to downregulate T helper type 2 (Th2)-type immune responses. Encapsulation of EGCG into the γ-PGA MN and utilization of L-ascorbic acid (AA) as a stabilizer preserved 95% of its structural stability and retained 93% of its initial antioxidant activity after 4 weeks of storage. Once-weekly administration of EGCG/AA-loaded MNs to an Nc/Nga mouse model of AD for 4 weeks significantly ameliorated skin lesions and epidermal hyperplasia by reducing serum IgE (from 12156 ± 1344 to 5555 ± 1362 ng/mL) and histamine levels (from 81 ± 18 to 40 ± 5 pg/mL) and inhibiting IFN-γ (from 0.10 ± 0.01 to 0.01 pg/mg total protein) and Th2-type cytokine production, when compared to the AD (no treatment) group (p < 0.05). Notably, once-weekly MN therapy was at least as effective as the daily topical application of an EGCG + AA solution but markedly reduced the administration frequency and required dose. These results show that EGCG/AA-loaded γ-PGA MNs may be a convenient and promising therapeutic option for AD treatment. STATEMENT OF SIGNIFICANCE: This study describes epigallocatechin gallate (EGCG)/L-ascorbic acid (AA)-loaded poly-γ-glutamate (γ-PGA) microneedles (MN) capable of providing antioxidant, anti-inflammatory, and immunomodulatory effects on inflamed skin for ameliorating atopic dermatitis (AD) symptoms in Nc/Nga mice. After skin insertion, the γ-PGA MN can be quickly dissolved in the skin and remain in the dermis for sustained release of encapsulated active ingredients for 6 days. We demonstrated that once-weekly MN therapy effectively alleviated skin lesions and modulated immune response to relieve Th2-polarized allergic response in mice. Once-weekly MN dosing regimen may provide patients with a more convenient, therapeutically equivalent option to daily topical dosing, and may increase compliance and long-term persistence with AD therapy.


Assuntos
Dermatite Atópica , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Catequina/análogos & derivados , Citocinas , Dermatite Atópica/tratamento farmacológico , Humanos , Imunidade , Camundongos , Ácido Poliglutâmico/análogos & derivados , Pele
19.
Bratisl Lek Listy ; 122(7): 507-512, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161119

RESUMO

OBJECTIVES: The aim of this study is to investigate the effect of two abundant dietary supplements, quercetin and vitamin C on some factors involved in metastasis and proliferation of prostate cancer, which are resistant to conventional chemotherapies in late stages. BACKGROUND: Bone and brain are two common sites of metastases in prostate cancer, nevertheless the factors involved in their metastatic pathways are not well understood. METHODS: The effect of quercetin (75µM) and vitamin C (100 µM) on CXCR4, CXCR7 chemokine receptors, α4, α5 and ß1 integrins, ki-67 proliferation marker and Vascular endothelial growth factor, VEGF was evaluated using Quantitative Reverse Transcription PCR (RT-qPCR). RESULTS: The effect of quercetin and vitamin C alone was different on PC3 and DU145 prostate cancer cell lines, but sequential combination reduced significantly the expression of CXCR and CXCR7 chemokine receptors, α4, α5 and ß1 integrin subunits, VEGF and Ki-67 proliferation markers in PC3 and DU145 cell lines. CONCLUSION: Our results indicated the beneficial effect of quercetin and vitamin C on prostate cancer cells with different metastatic sites and their differential response to the treatment which in turn may lead us to reach suitable therapeutic outcomes to combat cancer (Fig. 3, Ref. 36).


Assuntos
Neoplasias da Próstata , Quercetina , Ácido Ascórbico/farmacologia , Linhagem Celular Tumoral , Fibronectinas , Humanos , Integrinas , Masculino , Neoplasias da Próstata/tratamento farmacológico , Quercetina/farmacologia , Fator A de Crescimento do Endotélio Vascular
20.
Andrologia ; 53(8): e14120, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34028854

RESUMO

Occupational and ecological contacts to lead persist as a universal concern. Lead alters most of the physiological processes via enhancing oxidative stress. Thus, this study was purposed to assess the influence of turmeric (TMRC) and/or vitamin C (VIT-C) on Lead diacetate (Lead diAC)-induced testicular atrophy with an emphasis on oxidative stress, inflammation, BAX/STAR and GRP-78/17ß-HSD signalling. Rats were injected with Lead diAC and then treated with TMRC and/or VIT-C orally for 1 week. Lead diAC decreased serum testosterone and testicular glutathione levels. It also decreased superoxide dismutase activity. On the contrary, levels of malondialdehyde, tumour necrosis factor-α, IL-1ß and caspase-3 were increased. mRNA levels and protein expressions of GRP-78 and BAX were upregulated, while the expression of both steroidogenic acute regulatory protein and 17ß-HSD were downregulated. DNA fragmentation was increased as well. These changes were further confirmed by histopathological findings. Supplementation with TMRC and/or VIT-C ameliorated all of the above parameters. In Conclusion: TMRC or VIT-C specially in combination group prevents Lead diAC testicular damage via reduction of oxidative injury as well as inflammation, downregulation of GRP-78/BAX and upregulation of 17ß-HSD and STAR expression as well as improvement in the histological architecture of the testis.


Assuntos
Curcuma , Testículo , Animais , Ácido Ascórbico/farmacologia , Atrofia , Masculino , Compostos Organometálicos , Estresse Oxidativo , Ratos , Testículo/patologia , Testosterona/metabolismo
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