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1.
Biomed Pharmacother ; 139: 111660, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243628

RESUMO

The current study investigates the biochemical and histopathological effects of taxifolin on acrylamide-induced kidney damage. A 50 mg/kg dose of taxifolin was administered via oral gavage to the taxifolin + acrylamide (TACR) group (n-6) consisting of male albino Wistar rats. The same volume of distilled water used as solvent was orally administered to the acrylamide (ACR) (n-6) and healthy (HG) (n-6) groups. One hour after the administration of taxifolin and distilled water, a 20 mg/kg dose of acrylamide was orally administered to the TACR and ACR groups. This procedure was repeated once a day for 30 days. In the acrylamide group, malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels were found to be high, total glutathione (tGSH) levels were found to be low, and there was severe interstitial haemorrhage; additionally, tubular necrosis, tubular atrophy, leucocyte infiltration, and glomerular structures with expanded Bowman's space were observed. In the taxifolin group, where the increase of MDA, IL-1ß, and TNF-α and the decrease of tGSH associated with acrylamide have been prevented, any histopathological finding other than mild necrosis and atrophic tubules was not found. This suggests that Taxifolin would prevent kidney tissue from acrylamide-induced damage would be effective in treating acrylamide-induced nephrotoxicity, inhibiting the increase of MDA, IL-1ß and TNF-α, and decreasing tGSH associated with acrylamide.


Assuntos
Acrilamida/farmacologia , Inflamação/tratamento farmacológico , Nefropatias/tratamento farmacológico , Substâncias Protetoras/farmacologia , Quercetina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Animais , Antioxidantes/farmacologia , Glutationa/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
2.
Molecules ; 26(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199264

RESUMO

Rutin and its aglycone quercetin occur in the fruits, leaves, seeds, and grains of many plant species and are involved in plant herbivore interactions. We studied the effect of the exogenous application of rutin and quercetin on the probing behavior (= stylet penetration activities in plant tissues) of Acyrthosiphon pisum on Pisum sativum, Myzus persicae on Brassica rapa ssp. pekinensis, and Rhopalosiphum padi on Avena sativa using the electrical penetration graph technique (EPG = electropenetrography). The reaction of aphids to quercetin and rutin and the potency of the effect depended on aphid species, the flavonol, and flavonol concentration. Quercetin promoted probing activities of A. pisum within non-phloem and phloem tissues, which was demonstrated in the longer duration of probes and a trend toward longer duration of sap ingestion, respectively. M. persicae reached phloem in a shorter time on quercetin-treated B. rapa than on the control. Rutin caused a delay in reaching sieve elements by A. pisum and deterred probing activities of M. persicae within non-phloem tissues. Probing of R. padi was not affected by quercetin or rutin. The potency of behavioral effects increased as the applied concentrations of flavonols increased. The prospects of using quercetin and rutin in plant protection are discussed.


Assuntos
Afídeos/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Floema/fisiologia , Folhas de Planta/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Animais , Antioxidantes/farmacologia , Afídeos/fisiologia , Herbivoria
3.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202188

RESUMO

Various natural compounds have been successfully tested for preventing or counteracting the toxic effects of exposure to heavy metals. In this study, we analyzed the effects of cadmium chloride (CdCl2) on immortalized, non-tumorigenic thyroid cells Nthy-ori-3-1. We investigated the molecular mechanism underlying its toxic action as well as the potential protective effect of quercetin against CdCl2-induced damage. CdCl2 suppressed cell growth in a dose- and time-dependent manner (IC50 value ~10 µM) associated with a decrease in levels of phospho-ERK. In addition, CdCl2 elicited an increase in reactive oxygen species (ROS) production and lipid peroxidation. A significant increase in GRP78, an endoplasmic reticulum (ER) stress-related protein, was also observed. Supplementation of quercetin counteracted the growth-inhibiting action of CdCl2 by recovering ERK protein phosphorylation levels, attenuating ROS overproduction, decreasing MDA content and reducing the expression of GRP78 in cells exposed to CdCl2. Thus, in addition to revealing the molecular effects involved in cadmium-induced toxicity, the present study demonstrated, for the first time, a protective effect of quercetin against cadmium-induced damages to normal thyroid cells.


Assuntos
Cádmio/toxicidade , Disruptores Endócrinos/toxicidade , Substâncias Protetoras/farmacologia , Quercetina/farmacologia , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cloreto de Cádmio/toxicidade , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Glândula Tireoide/metabolismo
4.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206953

RESUMO

Quercetin, classified as a flavonoid, is a strong antioxidant that plays a significant role in the regulation of physiological processes in plants, which is particularly important in the case of biotic and abiotic stresses. The study investigated the effect of the use of potassium quercetin solutions in various concentrations (0.5%, 1.0%, 3.0% and 5.0%) on the physiological and biochemical properties of wheat seedlings. A pot experiment was carried out in order to determine the most beneficial dose of this flavonoid acting as a bio-stimulant for wheat plants. Spraying with quercetin derivative solutions was performed twice, and physiological measurements (chlorophyll content and fluorescence as well as gas exchange) were carried out on the first and seventh days after each application. The total phenolic compounds content and the total antioxidant capacity were also determined. It was shown that the concentrations of potassium quercetin applied have a stimulating effect on the course of physiological processes. In the case of most of the tested physiological parameters (chlorophyll content and fluorescence and gas exchange) and the total antioxidant capacity, no significant differences were observed in their increase as a result of application with concentrations of 3.0 and 5.0%. Therefore, the beneficial effect of quercetin on the analysed parameters is already observed when spraying with a concentration of 3.0%.


Assuntos
Antioxidantes/farmacologia , Quercetina/farmacologia , Triticum/efeitos dos fármacos , Clorofila/metabolismo , Produção Agrícola/métodos , Flavonoides/metabolismo , Fotossíntese , Quercetina/análogos & derivados , Plântula/efeitos dos fármacos , Plântula/metabolismo , Plântula/fisiologia , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
5.
Molecules ; 26(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204643

RESUMO

Plant-derived protein hydrolysates have potential applications in nutrition. Rice protein hydrolysates (RPHs), an excellent source of proteins, have attracted attention for the development of cosmeceuticals. However, few studies have reported the potential application of RPH in analysis, and this study examined their antioxidant activities and the inhibitory activities of skin aging enzymes. The results indicated that the total phenolic and flavonoid concentrations were 2.06 ± 0.13 mg gallic acid equivalent/g RPHs and 25.96 ± 0.52 µg quercetin equivalent/g RPHs, respectively. RPHs demonstrated dose-dependent activity for scavenging free radicals from 1,1-diphenyl-2-picrylhydrazyl [half-maximal inhibitory concentration (IC50) = 42.58 ± 2.1 mg/g RPHs] and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (IC50 = 2.11 ± 0.88 mg/g RPHs), dose-dependent reduction capacity (6.95 ± 1.40 mg vitamin C equivalent/g RPHs) and oxygen radical absorbance capacity (473 µmol Trolox equivalent/g RPHs). The concentrations of the RPH solution required to achieve 50% inhibition of hyaluronidase and tyrosinase activities were determined to be 8.91 and 107.6 mg/mL, respectively. This study demonstrated that RPHs have antioxidant, antihyaluronidase, and antityrosinase activities for future cosmetic applications.


Assuntos
Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Envelhecimento/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Clareadores/química , Clareadores/metabolismo , Flavonoides/farmacologia , Sequestradores de Radicais Livres/química , Ácido Gálico/farmacologia , Camundongos , Oryza/química , Oryza/enzimologia , Oryza/metabolismo , Oxirredução , Fenóis/farmacologia , Picratos/química , Picratos/farmacologia , Extratos Vegetais/química , Quercetina/farmacologia , Células RAW 264.7 , Ácidos Sulfônicos/química , Ácidos Sulfônicos/farmacologia , Tiazóis/química , Tiazóis/farmacologia
6.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208928

RESUMO

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 µM and 8 µM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile.


Assuntos
Antivirais/química , Quercetina/química , SARS-CoV-2/metabolismo , Selênio/química , Proteínas da Matriz Viral/antagonistas & inibidores , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Sítios de Ligação , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico , Chlorocebus aethiops , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , Quercetina/metabolismo , Quercetina/farmacologia , SARS-CoV-2/isolamento & purificação , Selênio/metabolismo , Células Vero , Proteínas da Matriz Viral/metabolismo , Replicação Viral/efeitos dos fármacos
7.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205604

RESUMO

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.


Assuntos
Colesterol/sangue , Colesterol/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Cricetinae , Flavonoides/farmacologia , Células Hep G2 , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Receptores de LDL/sangue , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Medicina (Kaunas) ; 57(6)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34204866

RESUMO

Background and Objectives: The most common kidney stones are calcium stones and calcium oxalate (CaOx) stones are the most common type of calcium stones. Hyperoxaluria is an essential risk factor for the formation of these stones. Quercetin is a polyphenol with antioxidant, anti-inflammatory, and many other physiological effects. The aim of this study was to investigate the protective effect of quercetin in hyperoxaluria-induced nephrolithiasis. Materials and Methods: Male Wistar-Albino rats weighing 250-300 g (n = 24) were randomized into three groups: Control (n = 8), ethylene glycol (EG) (n = 8), and EG + quercetin (n = 8). One percent EG-water solution was given to all rats except for the control group as drinking water for five weeks. Quercetin-water solution was given to the EG + quercetin group by oral gavage at a dose of 10 mg/kg/day. Malondialdehyde (MDA), catalase (CAT), urea, calcium, and oxalate levels were analyzed in blood and urine samples. Histopathological assessments and immunohistochemical analyses for oxidative stress and inflammation indicators p38 mitogen-activated protein kinase (p38-MAPK) and nuclear factor kappa B (NF-kB) were performed on renal tissues. Results: The MDA levels were significantly lower in the quercetin-treated group than in the EG-treated group (p = 0.001). Although CAT levels were higher in the quercetin-treated group than the EG-administered group, they were not significantly different between these groups. The expression of p38 MAPK was significantly less in the quercetin-treated group than the EG group (p < 0.004). There was no statistically significant difference between the quercetin and EG groups in terms of NF-kB expression. Conclusions: We conclude that hyperoxaluria activated the signaling pathways, which facilitate the oxidative processes leading to oxalate stone formation in the kidneys. Our findings indicated that quercetin reduced damage due to hyperoxaluria. These results imply that quercetin can be considered a therapeutic agent for decreasing oxalate stone formation, especially in patients with recurrent stones due to hyperoxaluria.


Assuntos
Hiperoxalúria , Cálculos Renais , Animais , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/tratamento farmacológico , Masculino , Estresse Oxidativo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar
9.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064664

RESUMO

Rutin is a flavonoid with antioxidant property. It has been shown to exert cardioprotection against cardiomyocyte hypertrophy. However, studies regarding its antihypertrophic property are still lacking, whether it demonstrates similar antihypertrophic effect to its metabolite, quercetin. Hence, this study aimed to investigate the effects of both flavonoids on oxidative stress and mitogen-activated protein kinase (MAPK) pathway in H9c2 cardiomyocytes that were exposed to angiotensin II (Ang II) to induce hypertrophy. Cardiomyocytes were exposed to Ang II (600 nM) with or without quercetin (331 µM) or rutin (50 µM) for 24 h. A group given vehicle served as the control. The concentration of the flavonoids was chosen based on the reported effective concentration to reduce cell hypertrophy or cardiac injury in H9c2 cells. Exposure to Ang II increased cell surface area, intracellular superoxide anion level, NADPH oxidase and inducible nitric oxide synthase activities, and reduced cellular superoxide dismutase activity and nitrite level, which were similarly reversed by both rutin and quercetin. Rutin had no significant effects on phosphorylated proteins of extracellular signal-related kinases (ERK1/2) and p38 but downregulated phosphorylated c-Jun N-terminal kinases (JNK1/2), which were induced by Ang II. Quercetin, on the other hand, had significantly downregulated the phosphorylated proteins of ERK1/2, p38, and JNK1/2. The quercetin inhibitory effect on JNK1/2 was stronger than the rutin. In conclusion, both flavonoids afford similar protective effects against Ang II-induced cardiomyocyte hypertrophy, but they differently modulate MAPK pathway.


Assuntos
Angiotensina II/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hipertrofia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mioblastos Cardíacos/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Animais , Antioxidantes/farmacologia , Células Cultivadas , Hipertrofia/induzido quimicamente , Hipertrofia/tratamento farmacológico , Hipertrofia/patologia , Proteínas Quinases Ativadas por Mitógeno/genética , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/efeitos dos fármacos , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Fosforilação , Ratos , Espécies Reativas de Oxigênio/metabolismo , Vasoconstritores/toxicidade
10.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064488

RESUMO

Quercetin is a poorly water-soluble flavonoid with many benefits to human health. Besides the natural food resources that may provide Quercetin, the interest in delivery systems that could enhance its bioavailability in the human body has seen growth in recent years. Promising delivery system candidates are represented by Solid Lipid Nanoparticles (SLNs) which are composed of well-tolerated compounds and provide a relatively high encapsulation efficiency and suitable controlled release. In this study, Quercetin-loaded and negatively charged Solid Lipid Nanoparticles were synthesized based on a coacervation method, using stearic acid as a core lipid and Arabic Gum as a stabilizer. Samples were qualitatively characterized by Dynamic light scattering (DLS), Zeta Potential, Surface infrared spectroscopy (FTIR-ATR), and Time of flight secondary ion mass spectrometry (ToF-SIMS). Encapsulation efficiency, drug release, and antioxidant effect against ABTS•+ were evaluated in vitro by UV-VIS spectrophotometry.


Assuntos
Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Quercetina/farmacologia , Antioxidantes/farmacologia , Preparações de Ação Retardada , Difusão Dinâmica da Luz , Tamanho da Partícula , Espectrometria de Massa de Íon Secundário , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Fatores de Tempo
11.
Molecules ; 26(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069439

RESUMO

Current pharmacological treatments for insomnia carry several and long-term side effects. Therefore, natural products without side effects are warranted. In this study, the sleep-promoting activity of the lotus leaf (Nelumbo nucifera) extract was assessed using ICR mice and Sprague Dawley rats. A pentobarbital-induced sleep test and electroencephalogram analysis were conducted to measure sleep latency time, duration, and sleep architecture. The action mechanism of the extract was evaluated through ligand binding experiments. A high dose (300 mg/kg) of the ethanolic lotus leaf extract significantly increased sleep duration compared to the normal group (p < 0.01). Administration of low (150 mg/kg) and high doses (300 mg/kg) of the extract significantly increased sleep quality, especially the relative power of theta waves (p < 0.05), compared to the normal group. Furthermore, caffeine and lotus leaf extract administration significantly recovered caffeine-induced sleep disruption (p < 0.001), and the sleep quality was similar to that of the normal group. Additionally, ligand binding assay using [3H]-flumazenil revealed that quercetin-3-O-glucuronide contained in the lotus leaf extract (77.27 µg/mg of extract) enhanced sleep by binding to GABAA receptors. Collectively, these results indicated that the lotus leaf extract, particularly quercetin-3-O-glucuronide, exhibits sleep quantity- and quality-enhancing activity via the GABAergic pathway.


Assuntos
Lotus/química , Folhas de Planta/química , Quercetina/análogos & derivados , Sono/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Etanol/química , Masculino , Camundongos Endogâmicos ICR , Quercetina/administração & dosagem , Quercetina/isolamento & purificação , Quercetina/farmacologia , Receptores de GABA-A/efeitos dos fármacos
12.
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
13.
Nucleic Acids Res ; 49(11): 6456-6473, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34107032

RESUMO

RNA-protein interactions are central to all gene expression processes and contribute to a variety of human diseases. Therapeutic approaches targeting RNA-protein interactions have shown promising effects on some diseases that are previously regarded as 'incurable'. Here, we developed a fluorescent on-bead screening platform, RNA Pull-Down COnfocal NAnoscanning (RP-CONA), to identify RNA-protein interaction modulators in eukaryotic cell extracts. Using RP-CONA, we identified small molecules that disrupt the interaction between HuR, an inhibitor of brain-enriched miR-7 biogenesis, and the conserved terminal loop of pri-miR-7-1. Importantly, miR-7's primary target is an mRNA of α-synuclein, which contributes to the aetiology of Parkinson's disease. Our method identified a natural product quercetin as a molecule able to upregulate cellular miR-7 levels and downregulate the expression of α-synuclein. This opens up new therapeutic avenues towards treatment of Parkinson's disease as well as provides a novel methodology to search for modulators of RNA-protein interaction.


Assuntos
Proteína Semelhante a ELAV 1/antagonistas & inibidores , MicroRNAs/antagonistas & inibidores , Quercetina/farmacologia , alfa-Sinucleína/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Proteína Semelhante a ELAV 1/metabolismo , Células HEK293 , Células HeLa , Humanos , MicroRNAs/metabolismo , Microscopia Confocal , RNA Mensageiro/metabolismo , alfa-Sinucleína/genética
14.
Molecules ; 26(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065200

RESUMO

Ribes nigrum L. (blackcurrant) leaf extracts, due to high levels of flavonols and anthocyanins, have been shown to exhibit beneficial effects in inflammatory diseases. However, whereas their traditional use has been investigated and validated in several models of inflammation and oxidative stress, the possible impact on skin disorders is still largely unknown. The purpose of this work was to elucidate the effects of R. nigrum leaf extract (RNLE) on keratinocyte-derived inflammatory mediators, elicited by a Th1 or Th2 cytokine milieu. HaCaT cells were challenged with TNF-α, either alone or in combination with the costimulatory cytokines IFN-γ or IL-4, and the release of proinflammatory cytokines and mediators (IL-8, IL-6, s-ICAM-1, and TSLP) was evaluated. The results showed that RNLE preferentially interferes with IFN-γ signaling, demonstrating only negligible activity on TNF-α or IL-4. This effect was attributed to flavonols, which might also account for the ability of RNLE to impair TNF-α/IL-4-induced TSLP release in a cAMP-independent manner. These results suggest that RNLE could have an antiallergic effect mediated in keratinocytes via mechanisms beyond histamine involvement. In conclusion, the discovery of RNLE preferential activity against IFN-γ-mediated inflammation suggests potential selectivity against Th1 type response and the possible use in Th1 inflammatory diseases.


Assuntos
Inflamação/induzido quimicamente , Interferon gama/farmacologia , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ribes/química , Linhagem Celular , Citocinas/administração & dosagem , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/administração & dosagem , Mediadores da Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Quempferóis/farmacologia , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Quercetina/farmacologia
15.
Colloids Surf B Biointerfaces ; 205: 111884, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34102529

RESUMO

Studies based on drug-DNA interactions, especially anticancer drug-DNA interactions, are of great importance for the method development. It is thought that single-use electrodes, which give fast, cheap and reproducible results, will make a great contribution to the chip technology for the development of individual patient analysis in the future. It is known that antioxidants reduce carcinogenesis caused by oxidative stress with their radical scavenging effects. Literature shows that quercetin (QRCT) exhibits anticancer activity by preventing oxidative cell damage as an effective radical scavenger. In this study, Bendamustine (BND), an anticancer drug, which is used in different blood cancer types, was electrochemically determined and the toxicity degree was calculated by examining the interaction of the drug with DNA in the absence and presence of QRCT, which is the first examination in the literature. Limit of detection and quantification for BND was calculated as 6.0 and 20.0 µg/mL respectively by using the equation I = 0.029 × CBND+ 1.197, (R2 = 0.997). We found that QRCT prevents the interaction between BND and DNA because of its strong interaction with DNA.


Assuntos
Antineoplásicos , Quercetina , Antineoplásicos/farmacologia , Cloridrato de Bendamustina , DNA , Dano ao DNA , Eletrodos , Humanos , Quercetina/farmacologia
16.
Molecules ; 26(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063645

RESUMO

Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx-Que (1:1) and Apx-Que-2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx-Que-2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx-Que was increased compared with the physical mixture and Apx, and Apx-Que remained stable in high temperature and illumination conditions. Therefore, a drug-drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.


Assuntos
Cristalização , Combinação de Medicamentos , Pirazóis/farmacologia , Piridonas/farmacologia , Quercetina/farmacologia , Solventes , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Fibrinolíticos/farmacologia , Ligação de Hidrogênio , Masculino , Preparações Farmacêuticas , Pós , Pirazóis/química , Piridonas/química , Quercetina/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Temperatura , Termogravimetria , Difração de Raios X
17.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063173

RESUMO

Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (ApcMin/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 107 CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in ApcMin/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/ß-catenin signaling pathway in the colon of ApcMin/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in ApcMin/+ mice.


Assuntos
Polipose Adenomatosa do Colo/metabolismo , Bifidobacterium bifidum/citologia , Carcinogênese/patologia , Células Imobilizadas/citologia , Neoplasias Colorretais/patologia , Lactobacillus gasseri/citologia , Quercetina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Colo/patologia , Contagem de Colônia Microbiana , Neoplasias Colorretais/genética , Metabolismo Energético/efeitos dos fármacos , Fezes/microbiologia , Comportamento Alimentar , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Sangue Oculto , Tamanho do Órgão/efeitos dos fármacos , Probióticos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
18.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068829

RESUMO

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.


Assuntos
Cassia/química , Infecções por HIV/tratamento farmacológico , Extratos Vegetais/farmacologia , Internalização do Vírus/efeitos dos fármacos , Catequina/farmacologia , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Ácido Oleanólico/farmacologia , Ácido Palmítico/farmacologia , Extratos Vegetais/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/virologia , Quercetina/análogos & derivados , Quercetina/farmacologia , Estilbenos/farmacologia
19.
Food Chem ; 358: 129812, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940289

RESUMO

Prunus fruits are recognized to be rich sources of polyphenols with health promoting effect. In this work we evaluated the phenolic profile and bioactivity, namely antioxidant capacity, antiproliferative effect in HT29, and inhibition capacity of α-glucosidase (α-Gls), α-amylase (α-Amy) and human dipeptidyl peptidase III (hDPP III) activities, of traditional Prunus fruits grown in Serbia. Fifteen Prunus samples were investigated and compared: common European plum and three old plum subspecies ('vlaskaca', damson plum and white damson), purple-leaf cherry plum, red and white cherry plum, sweet cherry, sweet cherry-wild type, sour cherry, steppe cherry, mahaleb cherry, blackthorn, peach, and apricot. Principal Component Analysis highlighted steppe cherry and blackthorn as Prunus species with the highest bioactive potential. In silico analysis pointed out rutinoside derivatives of cyanidin and quercetin as the most potent inhibitors of α-Gls, α-Amy and hDPP III enzymes. Quercetin 3-O-rutinoside showed the highest binding energy to α-Gls (-10.6 kcal/mol).


Assuntos
Antioxidantes/análise , Frutas/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Polifenóis/análise , Prunus/química , Antocianinas/análise , Antocianinas/farmacologia , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos/métodos , Glucosídeos/metabolismo , Glucosídeos/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Células HT29 , Humanos , Simulação de Acoplamento Molecular , Fenóis/análise , Polifenóis/farmacologia , Quercetina/análogos & derivados , Quercetina/metabolismo , Quercetina/farmacologia , alfa-Amilases/antagonistas & inibidores
20.
Food Chem ; 358: 129891, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940290

RESUMO

Quercetin is a well-studied natural product with multiple pharmacological properties. In this study, we demonstrated that quercetin suppressed protein digestion in the intestinal fluid by inhibiting trypsin, a key digestive enzyme. However, we also observed a previously unknown property of quercetin: promoting the intestinal absorption of proteins. In addition, the promoted protein absorption was mediated by internalization of digested oligopeptides in the intestinal epithelia rather than increasing the intestinal paracellular permeability. Notably, four other flavonoids also achieved such enhanced intestinal absorption, suggesting that this effect was associated with the aglycone flavonol backbone, but not related to their inhibitory potencies against trypsin. This study demonstrates that quercetin exhibits dual effects on protein digestion and absorption: 1) suppressing protein digestion by inhibiting trypsin in the intestinal fluid; 2) promoting the intestinal absorption of oligopeptides in the intestinal villi cells.


Assuntos
Proteínas na Dieta/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Quercetina/farmacologia , Animais , Líquidos Corporais/efeitos dos fármacos , Líquidos Corporais/metabolismo , Proteínas na Dieta/metabolismo , Digestão/efeitos dos fármacos , Cães , Flavonoides/farmacologia , Absorção Intestinal/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Células Madin Darby de Rim Canino , Masculino , Permeabilidade , Proteólise , Ratos Sprague-Dawley , Tripsina/metabolismo , Inibidores da Tripsina/farmacologia
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