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1.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500636

RESUMO

The African pumpkin (Momordica balsamina) contains bioactive phenolic compounds that may assist in reducing oxidative stress in the human body. The leaves are mainly consumed after boiling in water for a specific time; this hydrothermal process and conditions of the gastrointestinal tract may affect the presence and bioactivity of phenolics either positively or negatively. In this study, the effects of hydrothermal processing (boiling) and in vitro simulated human digestion on the phenolic composition, bioaccessibility and bioactivity in African pumpkin were investigated in comparison with those of spinach (Spinacia oleracea). A high-resolution ultra-performance liquid chromatography, coupled with diode array detection, quadrupole time-of-flight and mass spectrometer (UPLC-DAD-QTOF-MS) was used to profile phenolic metabolites. Metabolites such as 3-caffeoylquinic acid, 5-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid were highly concentrated in the boiled vegetable extracts compared to the raw undigested and all digested samples. The majority of African pumpkin and spinach extracts (non-digested and digested) protected Deoxyribonucleic acid (DNA), (mouse fibroblast) L929 and human epithelial colorectal adenocarcinoma (Caco-2) cells from 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative damage. From these results, the consumption of boiled African pumpkin leaves, as well as spinach, could be encouraged, as bioactive metabolites present may reduce oxidative stress in the body.


Assuntos
Cucurbita/química , Digestão/efeitos dos fármacos , Momordica/química , Fenóis/química , Fenóis/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/química , Células CACO-2 , Linhagem Celular Tumoral , Flavonoides/química , Humanos , Camundongos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Spinacia oleracea/química , Verduras/química
2.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500777

RESUMO

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken together, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elastase "super substrates" that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.


Assuntos
Imunidade Inata , Elastase de Leucócito/metabolismo , Metionina/análogos & derivados , Neutrófilos/imunologia , Biocatálise , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico/genética , Ensaios Enzimáticos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/genética , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Metionina/metabolismo , Simulação de Dinâmica Molecular , Infiltração de Neutrófilos , Neutrófilos/enzimologia , Oxirredução/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , SARS-CoV-2/imunologia , Especificidade por Substrato/imunologia
3.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360729

RESUMO

Mitochondria are considered to be important organelles in the cell and play a key role in the physiological function of the heart, as well as in the pathogenesis and development of various heart diseases. Under certain pathological conditions, such as cardiovascular diseases, stroke, traumatic brain injury, neurodegenerative diseases, muscular dystrophy, etc., mitochondrial permeability transition pore (mPTP) is formed and opened, which can lead to dysfunction of mitochondria and subsequently to cell death. This review summarizes the results of studies carried out by our group of the effect of astaxanthin (AST) on the functional state of rat heart mitochondria upon direct addition of AST to isolated mitochondria and upon chronic administration of AST under conditions of mPTP opening. It was shown that AST exerted a protective effect under all conditions. In addition, AST treatment was found to prevent isoproterenol-induced oxidative damage to mitochondria and increase mitochondrial efficiency. AST, a ketocarotenoid, may be a potential mitochondrial target in therapy for pathological conditions associated with oxidative damage and mitochondrial dysfunction, and may be a potential mitochondrial target in therapy for pathological conditions.


Assuntos
Sistemas de Liberação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Mitocôndrias Cardíacas/metabolismo , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/patologia , Humanos , Isoproterenol/efeitos adversos , Isoproterenol/uso terapêutico , Mitocôndrias Cardíacas/patologia , Oxirredução/efeitos dos fármacos , Xantofilas/uso terapêutico
4.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445486

RESUMO

Pharmacological and nutraceutical effects of isoflavones, which include genistein (GE), are attributed to their antioxidant activity protecting cells against carcinogenesis. The knowledge of the oxidation mechanisms of an active substance is crucial to determine its pharmacological properties. The aim of the present work was to explain complex oxidation processes that have been simulated during voltammetric experiments for our new thiolated genistein analog (TGE) that formed the self-assembled monolayer (SAM) on the gold electrode. The thiol linker assured a strong interaction of sulfur nucleophiles with the gold surface. The research comprised of the study of TGE oxidative properties, IR-ATR, and MALDI-TOF measurements of SAM before and after electrochemical oxidation. TGE has been shown to be electrochemically active. It undergoes one irreversible oxidation reaction and one quasi-reversible oxidation reaction in PBS buffer at pH 7.4. The oxidation of TGE results in electroactive products composed likely from TGE conjugates (e.g., trimers) as part of polymer. The electroactive centers of TGE and its oxidation mechanism were discussed using IR supported by quantum chemical and molecular mechanics calculations. Preliminary in-vitro studies indicate that TGE exhibits higher cytotoxic activity towards DU145 human prostate cancer cells and is safer for normal prostate epithelial cells (PNT2) than genistein itself.


Assuntos
Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Genisteína/farmacologia , Ouro/química , Compostos de Sulfidrila/química , Anticarcinógenos/química , Antioxidantes/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Genisteína/química , Humanos , Estrutura Molecular , Oxirredução/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445103

RESUMO

Here, we report the development of a novel photoactive biomolecular nanoarchitecture based on the genetically engineered extremophilic photosystem I (PSI) biophotocatalyst interfaced with a single layer graphene via pyrene-nitrilotriacetic acid self-assembled monolayer (SAM). For the oriented and stable immobilization of the PSI biophotocatalyst, an His6-tag was genetically engineered at the N-terminus of the stromal PsaD subunit of PSI, allowing for the preferential binding of this photoactive complex with its reducing side towards the graphene monolayer. This approach yielded a novel robust and ordered nanoarchitecture designed to generate an efficient direct electron transfer pathway between graphene, the metal redox center in the organic SAM and the photo-oxidized PSI biocatalyst. The nanosystem yielded an overall current output of 16.5 µA·cm-2 for the nickel- and 17.3 µA·cm-2 for the cobalt-based nanoassemblies, and was stable for at least 1 h of continuous standard illumination. The novel green nanosystem described in this work carries the high potential for future applications due to its robustness, highly ordered and simple architecture characterized by the high biophotocatalyst loading as well as simplicity of manufacturing.


Assuntos
Grafite/química , Microalgas/química , Nanoestruturas/química , Complexo de Proteína do Fotossistema I/química , Luz , Oxirredução/efeitos dos fármacos , Rodófitas/química , Transdução de Sinais/efeitos dos fármacos
6.
Molecules ; 26(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34299603

RESUMO

Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. In this scenario, the present study shows how the peel extract of mango-a tropical fruit rich in phytochemicals with nutraceutical properties-can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. By using hydro-alcoholic mango peel extract (MPE), we observed a consistent decline in thiol group content, which was accompanied by upregulation of MnSOD-a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane-such as voltage-dependent anion-selective channel (VDAC1), mitofilin, and some members of Bcl-2 family proteins (Mcl-1, Bcl-2 and Bcl-XL)-with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Mangifera , Mitocôndrias/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Mangifera/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução/efeitos dos fármacos , Extratos Vegetais/química
7.
ACS Appl Mater Interfaces ; 13(30): 35431-35443, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34304556

RESUMO

Stent implantation is the primary method used to treat coronary heart disease. However, it is associated with complications such as restenosis and late thrombosis. Despite surface modification being an effective way to improve the biocompatibility of stents, the current research studies are not focused on changes in the vascular microenvironment at the implantation site. In the present study, an adaptive drug-loaded coating was constructed on the surface of vascular stent materials that can respond to oxidative stress at the site of vascular lesions. Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium. EGCG has antioxidant activity, and pitavastatin calcium can inhibit smooth muscle cell proliferation. Therefore, EGCG and pitavastatin calcium provided a synergistic anti-inflammatory effect. Moreover, the coating was cross-linked using disulfide bonds, which accelerated the release of the drug in response to reactive oxygen species. A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo.


Assuntos
Stents Farmacológicos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Animais , Catequina/administração & dosagem , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Reestenose Coronária/prevenção & controle , Cistamina/administração & dosagem , Cistamina/química , Liberação Controlada de Fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Quinolinas/administração & dosagem , Quinolinas/química , Quinolinas/farmacologia , Coelhos , Ratos Sprague-Dawley , Aço Inoxidável/química
8.
Molecules ; 26(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299655

RESUMO

Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins' effects on inflammatory markers are promising and may have the potential to exert an anti-inflammatory effect in vitro and in vivo. Therefore, translating these research findings into clinical practice would effectively contribute to the prevention and treatment of chronic disease. The present narrative review summarizes the results of clinical studies from the last 5 years in the context of the anti-inflammatory and anti-oxidative role of anthocyanins in both health and disease. There is evidence to indicate that anthocyanins supplementation in the regulation of pro-inflammatory markers among the healthy and chronic disease population. Although the inconsistencies between the result of randomized control trials (RCTs) and meta-analyses were also observed. Regarding anthocyanins' effects on inflammatory markers, there is a need for long-term clinical trials allowing for the quantifiable progression of inflammation. The present review can help clinicians and other health care professionals understand the importance of anthocyanins use in patients with chronic diseases.


Assuntos
Antocianinas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Antocianinas/química , Anti-Inflamatórios/química , Antioxidantes/química , Doença Crônica , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Oxirredução/efeitos dos fármacos
9.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200914

RESUMO

Flavonoids are a group of secondary metabolites derived from plant-based foods, and they offer many health benefits in different stages of several diseases. This review will focus on their effects on ion channels expressed in vascular smooth muscle during atherosclerosis. Since ion channels can be regulated by redox potential, it is expected that during the onset of oxidative stress-related diseases, ion channels present changes in their conductive activity, impacting the progression of the disease. A typical oxidative stress-related condition is atherosclerosis, which involves the dysfunction of vascular smooth muscle. We aim to present the state of the art on how redox potential affects vascular smooth muscle ion channel function and summarize if the benefits observed in this disease by using flavonoids involve restoring the ion channel activity.


Assuntos
Aterosclerose/tratamento farmacológico , Flavonoides/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aterosclerose/metabolismo , Progressão da Doença , Humanos , Canais Iônicos/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Oxirredução/efeitos dos fármacos
10.
Molecules ; 26(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204618

RESUMO

There is scientific evidence of the positive effect of polyphenols from plant foods on inflammation and oxidative status. The aim of the present study was to investigate whether treatment with a high-polyphenolic nutraceutical reduces the plasmatic concentration of certain oxidative and inflammatory biomarkers in a healthy population. One hundred and eight subjects were selected and stratified by sex in the intervention group (n = 53) and the placebo group (n = 55). Ninety-two subjects completed the study after two 16-week treatment periods separated by a four-week washout period. The results revealed statistically significant differences in subjects treated with the polyphenolic extract compared to the placebo: A decrease in homocysteine, oxidized low-density lipoprotein (OxLDL), TNF-α, sTNFR1, and C-reactive protein (CRP). The most significant decrease was observed for OxLDL (from 78.98 ± 24.48 to 69.52 ± 15.64; p < 0.05) and CRP (from 1.50 ± 0.33 to 1.39 ± 0.37; p < 0.05), both showing significant differences compared to the placebo (p < 0.001). Moreover, catecholamines increased after the administration of the product under investigation, especially in the case of dopamine (from 15.43 ± 2.66 to 19.61 ± 5.73; p < 0.05). Therefore, the consumption of a nutraceutical based on fruit and vegetables with a high polyphenol content seems to improve the parameters related to health benefits (oxidative and inflammatory biomarkers), including remarkable changes in the expression of catecholamines.


Assuntos
Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Adulto , Antioxidantes/farmacologia , Biomarcadores/sangue , Catecolaminas/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Frutas/metabolismo , Humanos , Lipoproteínas LDL/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Placebos , Verduras/metabolismo
11.
Molecules ; 26(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207073

RESUMO

Laccases are multicopper oxidases that have shown a great potential in various biotechnological and green chemistry processes mainly due to their high relative non-specific oxidation of phenols, arylamines and some inorganic metals, and their high redox potentials that can span from 500 to 800 mV vs. SHE. Other advantages of laccases include the use of readily available oxygen as a second substrate, the formation of water as a side-product and no requirement for cofactors. Importantly, addition of low-molecular-weight redox mediators that act as electron shuttles, promoting the oxidation of complex bulky substrates and/or of higher redox potential than the enzymes themselves, can further expand their substrate scope, in the so-called laccase-mediated systems (LMS). Laccase bioprocesses can be designed for efficiency at both acidic and basic conditions since it is known that fungal and bacterial laccases exhibit distinct optimal pH values for the similar phenolic and aromatic amines. This review covers studies on the synthesis of five- and six-membered ring heterocyclic cores, such as benzimidazoles, benzofurans, benzothiazoles, quinazoline and quinazolinone, phenazine, phenoxazine, phenoxazinone and phenothiazine derivatives. The enzymes used and the reaction protocols are briefly outlined, and the mechanistic pathways described.


Assuntos
Compostos Heterocíclicos/síntese química , Lacase/química , Lacase/metabolismo , Bactérias/metabolismo , Biocatálise/efeitos dos fármacos , Fungos/metabolismo , Oxirredução/efeitos dos fármacos
12.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205408

RESUMO

As one of the nanostructures with enzyme-like activity, nanozymes have recently attracted extensive attention for their biomedical applications, especially for bacterial disinfection treatment. Nanozymes with high peroxidase activity are considered to be excellent candidates for building bacterial disinfection systems (nanozyme-H2O2), in which the nanozyme will promote the generation of ROS to kill bacteria based on the decomposition of H2O2. According to this criterion, a cerium oxide nanoparticle (Nanoceria, CeO2, a classical nanozyme with high peroxidase activity)-based nanozyme-H2O2 system would be very efficient for bacterial disinfection. However, CeO2 is a nanozyme with multiple enzyme-like activities. In addition to high peroxidase activity, CeO2 nanozymes also possess high superoxide dismutase activity and antioxidant activity, which can act as a ROS scavenger. Considering the fact that CeO2 nanozymes have both the activity to promote ROS production and the opposite activity for ROS scavenging, it is worth exploring which activity will play the dominating role in the CeO2-H2O2 system, as well as whether it will protect bacteria or produce an antibacterial effect. In this work, we focused on this discussion to unveil the role of CeO2 in the CeO2-H2O2 system, so that it can provide valuable knowledge for the design of a nanozyme-H2O2-based antibacterial system.


Assuntos
Bactérias/efeitos dos fármacos , Cério/farmacologia , Peróxido de Hidrogênio/farmacologia , Nanopartículas/química , Nanoestruturas/química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias/metabolismo , Oxirredução/efeitos dos fármacos , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
13.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205746

RESUMO

This work addressed the preservative behaviour of different icing media containing extracts from the alga Bifurcaria bifurcata. A comparative study of the antimicrobial and antioxidant effects of aqueous and ethanolic extracts of this macroalga was carried out. Whole hake (Merluccius merluccius) pieces were stored in ice containing either kind of extract and analysed for quality changes throughout a 13-day storage period. A progressive loss of microbial and biochemical quality was detected in all batches as chilling time increased. A significant inhibitory effect (p < 0.05) on microbial activity could be observed as a result of including the aqueous (lowering of psychrotrophic and lipolytic counts and pH value) and ethanolic (lowering of psychrotrophic and lipolytic counts) extracts. Additionally, both kinds of extract led to a substantial inhibition (p < 0.05) in the lipid hydrolysis rate (formation of free fatty acids), greater in the case of the batch containing ethanolic extract. Concerning lipid oxidation, a similar inhibitory effect (p < 0.05) on the formation of secondary compounds (thiobarbituric acid substances) was noticed in fish specimens corresponding to both alga extracts; however, more (p < 0.05) peroxide formation was detected in fish corresponding to the ethanolic extract batch. A preservative effect can be concluded for both kinds of extract; this effect agrees with previous studies reporting the presence of hydrophilic and lipophilic bioactive compounds in B. bifurcata.


Assuntos
Produtos Biológicos/farmacologia , Conservantes de Alimentos/farmacologia , Feófitas/efeitos dos fármacos , Alga Marinha/química , Animais , Antioxidantes/farmacologia , Produtos Biológicos/química , Etanol/química , Peixes , Conservação de Alimentos/métodos , Gadiformes , Oxirredução/efeitos dos fármacos , Alimentos Marinhos , Água/química
14.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34202966

RESUMO

Ginger (Zingiber officinale Roscoe, family: Zingiberaceae), originating in South-East Asia, is one of the most used spices and condiments for foods and beverages. It is also used in traditional medicine for many human disorders including fever, gastrointestinal complications, arthritis, rheumatism, hypertension, and various infectious diseases due to its anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties. Intriguingly, many recent studies evidenced the potent chemopreventive characteristics of ginger extracts against different types of cancer. The aim of this work is to review the literature related to the use of ginger extracts as a chemotherapeutic agent and to structure the cellular and molecular mechanisms through which ginger acts in different cancer types. Data summarized from experiments (in vitro or in vivo) and clinical studies, evidenced in this review, show that ginger derivatives perpetrate its anti-tumor action through important mediators, involved in crucial cell processes, such as cell cycle arrest, induction of cancer cell death, misbalance of redox homeostasis, inhibition of cell proliferation, angiogenesis, migration, and dissemination of cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Quimioprevenção , Gengibre/química , Neoplasias/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Quimioprevenção/métodos , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Oxirredução/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
15.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203038

RESUMO

Heavy metals are toxic environmental pollutants associated with severe ecological and human health risks. Among them is mercury (Hg), widespread in air, soil, and water, due to its peculiar geo-biochemical cycle. The clinical consequences of Hg exposure include neurotoxicity and nephrotoxicity. Furthermore, increased risk for cardiovascular diseases is also reported due to a direct effect on cardiovascular tissues, including endothelial cells, recently identified as important targets for the harmful action of heavy metals. In this review, we will discuss the rationale for the potential use of erythrocytes as a surrogate model to study Hg-related toxicity on the cardiovascular system. The toxic effects of Hg on erythrocytes have been amply investigated in the last few years. Among the observed alterations, phosphatidylserine exposure has been proposed as an underlying mechanism responsible for Hg-induced increased proatherogenic and prothrombotic activity of these cells. Furthermore, following Hg-exposure, a decrease in NOS activity has also been reported, with consequent lowering of NO bioavailability, thus impairing endothelial function. An additional mechanism that may induce a decrease in NO availability is the generation of an oxidative microenvironment. Finally, considering that chronic Hg exposure mainly occurs through contaminated foods, the protective effect of dietary components is also discussed.


Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiopatologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Metais Pesados/toxicidade , Animais , Vasos Sanguíneos/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Suscetibilidade a Doenças , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Poluentes Ambientais/efeitos adversos , Humanos , Mercúrio/toxicidade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
16.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202112

RESUMO

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.


Assuntos
Benzoquinonas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Curcumina/farmacologia , Galactose/farmacologia , Miocárdio/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Benzoquinonas/química , Curcumina/química , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Especificidade de Órgãos , Ratos , Relação Estrutura-Atividade
17.
Biomed Pharmacother ; 139: 111718, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243619

RESUMO

BACKGROUND: The field bean (Vicia faba) is a valuable fodder plant of the Fabaceae family, grown as a main crop for its seed yield. Its phytochemical profile is characterized by the presence of a range of compounds with various biological activities. PURPOSE: The present study investigates the phytochemical profile of the extract from mature seeds of Vicia faba var. minor and examines its impact on preventing oxidative damage to various lipids, protein and DNA molecules in vitro. METHODS: Human plasma was treated with H2O2/Fe (an OH. donor) to induce oxidative damage to lipids and proteins, and the plant extract was then added. As oxidative stress may influence the biological activity of plasma, e.g. coagulation, and influence cardiovascular disease, the study also examined the effect of the plant extract on coagulation and monoamine oxidase activity (MAO, EC 1.4.3.4). RESULTS: The tested extract exerted a protective effect on plasma lipids and proteins treated with H2O2/Fe. However, while it appears to effectively protect the DNA in peripheral blood mononuclear cells from oxidative damage, it did not induce changes in the coagulation process, and significantly reduced MAO activity when applied at 1, 5, and 10 µg/mL. It is possible that the observed antioxidant potential may be due to the complex chemical composition of the extract: the phytochemical profile demonstrated a range of phenolic compounds, including catechins. CONCLUSION: Our findings indicate that extract from mature seeds of V. faba var. minor may be a promising source of antioxidants in multiple applications, including diseases associated with oxidative stress; however, more studies based on in vitro and in vivo models are needed to determine its biological properties.


Assuntos
Antioxidantes/fisiologia , Células Sanguíneas/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Sementes/química , Vicia faba/química , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia
18.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073033

RESUMO

Atrial fibrillation (AF) is the most common sustained (atrial) arrhythmia, a considerable global health burden and often associated with heart failure. Perturbations of redox signalling in cardiomyocytes provide a cellular substrate for the manifestation and maintenance of atrial arrhythmias. Several clinical trials have shown that treatment with sodium-glucose linked transporter inhibitors (SGLTi) improves mortality and hospitalisation in heart failure patients independent of the presence of diabetes. Post hoc analysis of the DECLARE-TIMI 58 trial showed a 19% reduction in AF in patients with diabetes mellitus (hazard ratio, 0.81 (95% confidence interval: 0.68-0.95), n = 17.160) upon treatment with SGLTi, regardless of pre-existing AF or heart failure and independent from blood pressure or renal function. Accordingly, ongoing experimental work suggests that SGLTi not only positively impact heart failure but also counteract cellular ROS production in cardiomyocytes, thereby potentially altering atrial remodelling and reducing AF burden. In this article, we review recent studies investigating the effect of SGLTi on cellular processes closely interlinked with redox balance and their potential effects on the onset and progression of AF. Despite promising insight into SGLTi effect on Ca2+ cycling, Na+ balance, inflammatory and fibrotic signalling, mitochondrial function and energy balance and their potential effect on AF, the data are not yet conclusive and the importance of individual pathways for human AF remains to be established. Lastly, an overview of clinical studies investigating SGLTi in the context of AF is provided.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Miócitos Cardíacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Animais , Cálcio/metabolismo , Células Cultivadas , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Espécies Reativas de Oxigênio/metabolismo
19.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064423

RESUMO

In the present study, we evaluated for the first time the photoprotective effect of fish bone bioactive peptides (FBBP) preparation isolated from silver carp (Hypophthalmichthys molitrix) discarded tissue using in vitro experimental models of skin cells exposed to ultraviolet B (UVB) irradiation and stressing agents. FBBP preparation was obtained by papain treatment of minced bones and centrifugal ultrafiltration, and the molecular weight (MW) distribution was characterized by size exclusion and reversed-phase high performance liquid chromatography (RP-HPLC). In vitro assessment of the effect of FBBP pretreatment in UVB-irradiated L929 fibroblasts and HaCaT keratinocytes revealed their cytoprotective activity. Their capacity to efficiently reduce reactive oxygen species (ROS) production and lipid peroxidation varied in a dose-dependent manner, and it was greater in fibroblasts. A decrease of proinflammatory cytokines secretion, in particular of tumor necrosis factor alpha (TNF-α), was found after FBBP pretreatment of THP-1-derived inflamed macrophages. Melanin production and tyrosinase activity investigated in UVB-irradiated Mel-Juso cells were lowered in direct relation to FBBP concentrations. FBBP fractions with high radical scavenging activity were separated by ion exchange chromatography, and two collagenic sequences were identified. All these results offer new scientific data on aquaculture fish bone-derived peptides confirming their ability to control the antioxidant, anti-inflammatory and pigmentation processes developed during UV irradiation of skin cells and recommend their use as valuable natural ingredients of photoprotective cosmeceutical products.


Assuntos
Osso e Ossos/efeitos dos fármacos , Inflamação/patologia , Peptídeos/farmacologia , Pigmentação , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Citoproteção/efeitos dos fármacos , Citoproteção/efeitos da radiação , Peixes , Células HaCaT/efeitos dos fármacos , Células HaCaT/efeitos da radiação , Humanos , Mediadores da Inflamação/metabolismo , Espaço Intracelular/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Malondialdeído/metabolismo , Melaninas/biossíntese , Camundongos , Peso Molecular , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Peptídeos/isolamento & purificação , Pigmentação/efeitos dos fármacos , Pigmentação/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta , Células THP-1
20.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063915

RESUMO

The present report was designed to determine the antioxidant and antigenotoxic effects of phaseolin (isolated from Phaseolus vulgaris) against mouse colon and liver damage induced by azoxymethane (AOM) and its colon chemopreventive effect. Eight groups with 12 mice each were utilized for an eight-week experiment: the control group was intragastrically (ig) administered 0.9% saline solution; the positive control group was intraperitoneally (ip) injected with 7.5 mg/kg AOM twice a week (weeks three and four of the experiment); three groups were ig administered each day with phaseolin (40, 200, and 400 mg/kg); and three groups were ig administered phaseolin daily (40, 200, and 400 mg/kg) plus 7.5 mg/kg AOM twice a week in weeks three and four of the experiment. The results showed that phaseolin did not produce oxidative stress, DNA damage, or aberrant crypts; in contrast, 100% inhibition of lipoperoxidation, protein oxidation, and nitrites induction generated by AOM was found in both organs, and DPPH radical capture occurred. The two highest phaseolin doses reduced DNA damage induced by AOM in both organs by more than 90% and reduced the AOM-induced aberrant crypts by 84%. Therefore, our study demonstrated the strong in vivo antioxidant, antigenotoxic, and chemopreventive potential of phaseolin.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Colite/prevenção & controle , Phaseolus/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Focos de Criptas Aberrantes/prevenção & controle , Animais , Antioxidantes , Azoximetano , Quimioprevenção , Colite/induzido quimicamente , Colo , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sementes/química
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