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1.
J Infect Public Health ; 14(9): 1179-1185, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34399189

RESUMO

This systematic review aims to evaluate the evidence on the efficacy of mouth rinses on SARS-CoV-2 from in vitro studies. Five electronic databases were searched up to February 2021; no language or time restrictions were used. Two independent reviewers conducted both selection and data extraction processes. The toxicological data reliability assessment tool was used to evaluate the risk of bias. Starting from 239 articles, retrieved by the electronic search, only eight studies were included in our systematic review. Povidone Iodine (PVP-I) was effective in killing SARS-CoV-2, demonstrated higher virucidal activity than other commonly used active ingredients. Conflicting results were found about the effectiveness of Chlorhexidine (CHX) while hydrogen peroxide (H2O2) proved less effective than PVP-I. Other active ingredients, such as quaternary ammonium compounds and Ethanol (particularly when combined with essential oils), have also shown promising results in reducing viral load, with results comparable to PVP-I.


Assuntos
Anti-Infecciosos Locais , COVID-19 , Anti-Infecciosos Locais/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Antissépticos Bucais/farmacologia , Reprodutibilidade dos Testes , SARS-CoV-2
2.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361702

RESUMO

Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin-coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11-18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H2O2 in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained.


Assuntos
Antioxidantes/síntese química , Inibidores da Colinesterase/síntese química , Cumarínicos/síntese química , Curcumina/análogos & derivados , Inibidores da Monoaminoxidase/síntese química , Fármacos Neuroprotetores/síntese química , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Butirilcolinesterase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Cumarínicos/farmacologia , Curcumina/farmacologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Córtex Motor/citologia , Córtex Motor/enzimologia , Nanopartículas/química , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Fármacos Neuroprotetores/farmacologia , Picratos/antagonistas & inibidores , Cultura Primária de Células , Ratos , Relação Estrutura-Atividade
3.
Molecules ; 26(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34443598

RESUMO

Apocynin (APO) is a known multi-enzymatic complexed compound, employed as a viable NADPH oxidase (NOX) inhibitor, extensively used in both traditional and modern-day therapeutic strategies to combat neuronal disorders. However, its therapeutic efficacy is limited by lower solubility and lesser bioavailability; thus, a suitable nanocarrier system to overcome such limitations is needed. The present study is designed to fabricate APO-loaded polymeric nanoparticles (APO-NPs) to enhance its therapeutic efficacy and sustainability in the biological system. The optimized APO NPs in the study exhibited 103.6 ± 6.8 nm and -13.7 ± 0.43 mV of particle size and zeta potential, respectively, along with further confirmation by TEM. In addition, the antioxidant (AO) abilities quantified by DPPH and nitric oxide scavenging assays exhibited comparatively higher AO potential of APO-NPs than APO alone. An in-vitro release profile displayed a linear diffusion pattern of zero order kinetics for APO from the NPs, followed by its cytotoxicity evaluation on the PC12 cell line, which revealed minimal toxicity with higher cell viability, even after treatment with a stress inducer (H2O2). The stability of APO-NPs after six months showed minimal AO decline in comparison to APO only, indicating that the designed nano-formulation enhanced therapeutic efficacy for modulating NOX-mediated ROS generation.


Assuntos
Acetofenonas/química , Acetofenonas/farmacologia , Peróxido de Hidrogênio/farmacologia , NADPH Oxidases/metabolismo , Nanopartículas/química , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Neurônios/citologia , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos
4.
Life Sci ; 283: 119864, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358548

RESUMO

AIMS: The study examined that morin as possible antioxidant and neuroprotective due to oxidative stress (H2O2) in zebrafish larval model. MATERIALS AND METHODS: Zebrafish larvae were induced with oxidative stress using H2O2 at 1 mM; their behavioural changes were assessed through partition preference and horizontal compartment test. The head section without eyes and yolk sac of zebrafish larvae were employed for enzyme assays such as SOD, CAT, Thiobarbituric acid reactive substances assay, reduced glutathione, glutathione peroxidase activity, glutathione S transferase, Acetylcholinesterase activity and nitrate levels. Also, intracellular ROS and apoptosis in larval head was detected by DCFDA and acridine orange staining followed by gene expression studies. KEY FINDINGS: Morin exposure was not harmful to the larvae at concentration between 20 and 60 µM, but it caused non-lethal deformity between 80 and 100 µM. In the partition test, zebrafish embryos treated with H2O2 showed cognitive impairment, whereas the morin-treated groups showed an improved behavioural activity. The study also found that restoring antioxidant enzymes and reduced lipid peroxidation which had a neuroprotective impact. Inhibition of NO overproduction and increased AChE activity were also shown to reduce the neuronal damage. Apoptosis and intracellular ROS levels were reduced in larvae when it was co-incubated with morin. Morin treatment up regulated the antioxidant enzymes against oxidative stress. SIGNIFICANCE: Morin provides protection against H2O2 induced oxidative stress through a cellular antioxidant defence mechanism by up-regulating gene expression, thus increasing the antioxidant activity at cellular or organismal stage.


Assuntos
Antioxidantes/farmacologia , Embrião não Mamífero/metabolismo , Flavonoides/farmacologia , Síndromes Neurotóxicas , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/patologia , Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/embriologia , Síndromes Neurotóxicas/patologia
5.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445561

RESUMO

Among numerous contaminants, the ubiquitous occurrence of nonsteroidal anti-inflammatory drugs (NSAIDs) in the environment and their plausible harmful impact on nontarget organisms have made them one of the most important areas of concern in recent years. Crop plants can also potentially be exposed to NSAIDs, since the concentration of these pharmaceuticals is constantly rising in the surface water and soil. Our goal was to evaluate the stress response of two crop plants, maize and tomato, to treatment with selected NSAIDs, naproxen and diclofenac. The focus of the research was on the growth response, photosynthetic efficiency, selected oxidative stress factors (such as the H2O2 level and the rate of lipid peroxidation) as well as the total phenolic content, which represents the non-enzymatic protectants against oxidative stress. The results indicate that susceptibility to the NSAIDs that were tested is dependent on the plant species. A higher sensitivity of tomato manifested in growth inhibition, a decrease in the content of the photosynthetic pigments and a reduction in the maximum quantum efficiency of PSII and the activity of PSII, which was estimated using the Fv/Fm and Fv/F0 ratios. Based on the growth results, it was also possible to reveal that diclofenac had a more toxic effect on tomato. In contrast to tomato, in maize, neither the content of the photosynthetic pigments nor growth appeared to be affected by DFC and NPX. However, both drugs significantly decreased in maize Fv and Fm, which are particularly sensitive to stress. A higher H2O2 concentration accompanied, in most cases, increasing lipid peroxidation, indicating that oxidative stress occurred in response to the selected NSAIDs in the plant species that were studied. The higher phenolic content of the plants after NSAIDs treatment may, in turn, indicate the activation of defense mechanisms in response to the oxidative stress that is triggered by these drugs.


Assuntos
Diclofenaco/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lycopersicon esculentum/efeitos dos fármacos , Naproxeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Zea mays/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Peróxido de Hidrogênio/farmacologia , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/metabolismo , Oxidantes/farmacologia , Fenóis/farmacologia , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo
6.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443533

RESUMO

Quercetin is a polyphenolic compound, the effects of which raise scientists' doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).


Assuntos
Membrana Celular/efeitos dos fármacos , Neuroblastoma/patologia , Quercetina/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , L-Lactato Desidrogenase/metabolismo , Ozônio/farmacologia , Pressão , Temperatura
7.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203307

RESUMO

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.


Assuntos
Peróxido de Hidrogênio/farmacologia , Maclura/química , NF-kappa B/metabolismo , Extratos Vegetais/química , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
Biomolecules ; 11(7)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209255

RESUMO

Various environmental stimuli, including oxidative stress, could lead to granulosa cell (GC) death through mitophagy. Recently, it was reported that melatonin (MEL) has a significant effect on GC survival during oxidative damage. Here, we found that MEL inhibited oxidative stress-induced mitophagy to promote GC survival. The loss of cell viability upon H2O2 exposure was significantly restored after MEL treatment. Concomitantly, MEL inhibited the activation of mitophagy during oxidative stress. Notably, blocking mitophagy repressed GC death caused by oxidative stress. However, MEL cannot further restore viability of cells treated with mitophagy inhibitor. Moreover, PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase, was inhibited by MEL during oxidative stress. As a result, the E3 ligase Parkin failed to translocate to mitochondria, leading to impaired mitochondria clearance. Using RNAi to knock down PINK1 expression, we further verified the role of the MEL-PINK1-Parkin (MPP) pathway in maintaining GC survival by suppressing mitophagy. Our findings not only clarify the protective mechanisms of MEL against oxidative damage in GCs, but also extend the understanding about how circadian rhythms might influence follicles development in the ovary. These findings reveal a new mechanism of melatonin in defense against oxidative damage to GCs by repressing mitophagy, which may be a potential therapeutic target for anovulatory disorders.


Assuntos
Células da Granulosa/metabolismo , Melatonina/farmacologia , Mitofagia/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células da Granulosa/fisiologia , Peróxido de Hidrogênio/farmacologia , Masculino , Melatonina/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Substâncias Protetoras/farmacologia , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
9.
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
10.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298945

RESUMO

Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress-induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 µM for double time) and D-galactose (D-Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow-mesenchymal stem cells (hBM-MSCs) and mice, respectively. We performed the SA-ß-gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress-induced senescence by upregulating AMPK-mediated activation of autophagy in hBM-MSCs. D-Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti-senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress-induced senescence.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Senescência Celular/efeitos dos fármacos , Chalconas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Cardiotônicos/farmacologia , Células Cultivadas , Galactose/metabolismo , Coração/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Plant Sci ; 310: 110981, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34315597

RESUMO

Signal molecule hydrogen peroxide (H2O2) plays critical roles in various processes of plant development. However, H2O2 signaling network, especially the responders that sense and respond to the H2O2 signal remain largely unknown. Here we report two homologous genes H2O2 Response Gene 1 and 2 (HRG1/2) in Arabidopsis that could quickly respond to exogenous or endogenous H2O2. Knockdown of HRG1/2 facilitated seed germination while overexpression of HRG1/2 greatly retarded seed germination. ROS level in HRG1 overexpression roots was significantly lower than that in HRG1/2 mutants after H2O2 treatment. The expression level of enzymatic antioxidant DHAR3 was upregulated in HRG1 overexpression plants, suggesting that DHAR3 is downstream of HRG1. That the root meristem length and cell number were significantly reduced in hrg1-1 and hrg2-1 plants upon H2O2 treatment compared to that of HRG1 overexpression plants also approves the idea that HRGs function in H2O2 removal. Further evolutionary analysis indicates that this is a dicotyledon-specific pathway responsive to H2O2. Together, this work reveals HRG1/2 as novel H2O2 responders involved in ROS scavenging to ensure embryonic root meristem activity. These findings provide valuable clues for the of H2O2 signaling and root meristem regulation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Peróxido de Hidrogênio/farmacologia , Meristema/efeitos dos fármacos , Meristema/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
12.
Molecules ; 26(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204227

RESUMO

Anneslea fragrans Wall., commonly known as "Pangpo Tea", is traditionally used as a folk medicine and healthy tea for the treatment of liver and intestine diseases. The aim of this study was to purify the antioxidative and cytoprotective polyphenols from A. fragrans leaves. After fractionation with polar and nonpolar organic solvents, the fractions of aqueous ethanol extract were evaluated for their total phenolic (TPC) and flavonoid contents (TFC) and antioxidant activities (DPPH, ABTS, and FRAP assays). The n-butanol fraction (BF) showed the highest TPC and TFC with the strongest antioxidant activity. The bio-guided chromatography of BF led to the purification of six flavonoids (1-6) and one benzoquinolethanoid (7). The structures of these compounds were determined by NMR and MS techniques. Compound 6 had the strongest antioxidant capacity, which was followed by 5 and 2. The protective effect of the isolated compounds on hydrogen peroxide (H2O2)-induced oxidative stress in HepG2 cells revealed that the compounds 5 and 6 exhibited better protective effects by inhibiting ROS productions, having no significant difference with vitamin C (p > 0.05), whereas 6 showed the best anti-apoptosis activity. The results suggest that A. fragrans could serve as a valuable antioxidant phytochemical source for developing functional food and health nutraceutical products.


Assuntos
Ericales/química , Estresse Oxidativo/efeitos dos fármacos , Fenóis/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , China , Flavonoides/farmacologia , Células Hep G2 , Humanos , Peróxido de Hidrogênio/farmacologia , Fenóis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Polifenóis/farmacologia
13.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205973

RESUMO

The Arabidopsis AtCRK5 protein kinase is involved in the establishment of the proper auxin gradient in many developmental processes. Among others, the Atcrk5-1 mutant was reported to exhibit a delayed gravitropic response via compromised PIN2-mediated auxin transport at the root tip. Here, we report that this phenotype correlates with lower superoxide anion (O2•-) and hydrogen peroxide (H2O2) levels but a higher nitric oxide (NO) content in the mutant root tips in comparison to the wild type (AtCol-0). The oxidative stress inducer paraquat (PQ) triggering formation of O2•- (and consequently, H2O2) was able to rescue the gravitropic response of Atcrk5-1 roots. The direct application of H2O2 had the same effect. Under gravistimulation, correct auxin distribution was restored (at least partially) by PQ or H2O2 treatment in the mutant root tips. In agreement, the redistribution of the PIN2 auxin efflux carrier was similar in the gravistimulated PQ-treated mutant and untreated wild type roots. It was also found that PQ-treatment decreased the endogenous NO level at the root tip to normal levels. Furthermore, the mutant phenotype could be reverted by direct manipulation of the endogenous NO level using an NO scavenger (cPTIO). The potential involvement of AtCRK5 protein kinase in the control of auxin-ROS-NO-PIN2-auxin regulatory loop is discussed.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Ácidos Indolacéticos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptores de Superfície Celular/genética , Arabidopsis/crescimento & desenvolvimento , Transporte Biológico/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Gravitação , Gravitropismo/genética , Peróxido de Hidrogênio/farmacologia , Meristema/genética , Meristema/crescimento & desenvolvimento , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paraquat/farmacologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Molecules ; 26(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203560

RESUMO

A number of plants used in folk medicine in Thailand and Eastern Asia are attracting interest due to the high bioactivities of their extracts. The aim of this study was to screen the edible leaf extracts of 20 plants found in Thailand and investigate the potential neuroprotective effects of the most bioactive sample. The total phenol and flavonoid content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity were determined for all 20 leaf extracts. Based on these assays, Glochidion littorale leaf extract (GLE), which showed a high value in all tested parameters, was used in further experiments to evaluate its effects on neurodegeneration in Caenorhabditis elegans. GLE treatment ameliorated H2O2-induced oxidative stress by attenuating the accumulation of reactive oxygen species and protected the worms against 1-methyl-4-phenylpyridinium-induced neurodegeneration. The neuroprotective effects observed may be associated with the activation of the transcription factor DAF-16. The characterization of this extract by LC-MS identified several phenolic compounds, including myricetin, coumestrin, chlorogenic acid, and hesperidin, which may play a key role in neuroprotection. This study reports the novel neuroprotective activity of GLE, which may be used to develop treatments for neurodegenerative diseases such as Parkinson's syndrome.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Fármacos Neuroprotetores , Estresse Oxidativo/efeitos dos fármacos , Phyllanthus/química , Extratos Vegetais , Animais , Peróxido de Hidrogênio/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
15.
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
16.
Nat Microbiol ; 6(7): 842-851, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34083769

RESUMO

The emergent fungal pathogen Candida auris exhibits high resistance to antifungal drugs and environmental stresses, impeding treatment and decontamination1-3. The fungal factors mediating this stress tolerance are largely unknown. In the present study, we performed piggyBac, transposon-mediated, genome-wide mutagenesis and genetic screening in C. auris, and identified a mutant that grew constitutively in the filamentous form. Mapping the transposon insertion site revealed the disruption of a long non-coding RNA, named DINOR for DNA damage-inducible non-coding RNA. Deletion of DINOR caused DNA damage and an upregulation of genes involved in morphogenesis, DNA damage and DNA replication. The DNA checkpoint kinase Rad53 was hyperphosphorylated in dinorΔ mutants, and deletion of RAD53 abolished DNA damage-induced filamentation. DNA-alkylating agents, which cause similar filamentous growth, induced DINOR expression, suggesting a role for DINOR in maintaining genome integrity. Upregulation of DINOR also occurred during exposure to the antifungal drugs caspofungin and amphotericin B, macrophages, H2O2 and sodium dodecylsulfate, indicating that DINOR orchestrates multiple stress responses. Consistently, dinorΔ mutants displayed increased sensitivity to these stresses and were attenuated for virulence in mice. Moreover, genome-wide genetic interaction studies revealed links between the function of DINOR and TOR signalling, an evolutionarily conserved pathway that regulates the stress response. Identification of the mechanism(s) by which DINOR regulates stress responses in C. auris may provide future opportunities for the development of therapeutics.


Assuntos
Candida/patogenicidade , RNA Fúngico/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Virulência/metabolismo , Animais , Antifúngicos/farmacologia , Candida/genética , Candida/crescimento & desenvolvimento , Candidíase/microbiologia , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Dano ao DNA , Replicação do DNA , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação da Expressão Gênica , Peróxido de Hidrogênio/farmacologia , Camundongos , Morfogênese , Mutação , Fosforilação , RNA Fúngico/genética , RNA Longo não Codificante/genética , Virulência , Fatores de Virulência/genética
17.
Molecules ; 26(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066799

RESUMO

Honey has good antimicrobial properties and can be used for medical treatment. The antimicrobial properties of unifloral honey varieties are different. In this study, we evaluated the antimicrobial and antioxidant activities of nine kinds of Chinese monofloral honeys. In addition, headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) technology was used to detect their volatile components. The relevant results are as follows: 1. The agar diffusion test showed that the diameter of inhibition zone against Staphylococcus aureus of Fennel honey (21.50 ± 0.41 mm), Agastache honey (20.74 ± 0.37 mm), and Pomegranate honey (18.16 ± 0.11 mm) was larger than that of Manuka 12+ honey (14.27 ± 0.10 mm) and Manuka 20+ honey (16.52 ± 0.12 mm). The antimicrobial activity of Chinese honey depends on hydrogen peroxide. 2. The total antioxidant capacity of Fennel honey, Agastache honey, and Pomegranate honey was higher than that of other Chinese honeys. There was a significant positive correlation between the total antioxidant capacity and the total phenol content of Chinese honey (r = 0.958). The correlation coefficient between the chroma value of Chinese honey and the total antioxidant and the diameter of inhibition zone was 0.940 and 0.746, respectively. The analyzed dark honeys had better antimicrobial and antioxidant activities. 3. There were significant differences in volatile components among Fennel honey, Agastache honey, Pomegranate honey, and Manuka honey. Hexanal-D and Heptanol were the characteristic components of Fennel honey and Pomegranate honey, respectively. Ethyl 2-methylbutyrate and 3-methylpentanoic acids were the unique compounds of Agastache honey. The flavor fingerprints of the honey samples from different plants can be successfully built using HS-GC-IMS and principal component analysis (PCA) based on their volatile compounds. Fennel honey, Agastache honey, and Pomegranate honey are Chinese honey varieties with excellent antimicrobial properties, and have the potential to be developed into medical grade honey.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Mel/análise , Mel/classificação , Staphylococcus aureus/efeitos dos fármacos , Agastache/química , Antibacterianos/química , Antioxidantes/química , China , Cromatografia Gasosa , Foeniculum/química , Peróxido de Hidrogênio/farmacologia , Espectrometria de Mobilidade Iônica , Leptospermum/química , Testes de Sensibilidade Microbiana , Fenóis/farmacologia , Romã (Fruta)/química
18.
J Med Chem ; 64(13): 9166-9181, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34132541

RESUMO

Timely myocardial reperfusion salvages ischemic myocardium from infarction, whereas reperfusion itself induces cardiomyocyte death, which is called myocardial ischemia/reperfusion (MI/R) injury. Herein, ß-carboline derivative 17c was designed and synthesized with obvious myocardial protective activity for the first time. Pretreatment of 17c effectively protected the cardiomyocyte H9c2 cells from H2O2-induced lactate dehydrogenase leakage and restored the endogenous antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Besides, 17c effectively protected the mitochondria through decreasing the reactive oxygen species overproduction and enhancing the mitochondrial membrane potential. As a result, 17c significantly reduced the necrosis of cardiomyocytes in H2O2-induced oxidative stress, which was more potent than polydatin. In MI/R injury rats, 17c pretreatment obviously increased the levels of SOD and GSH-Px and inhibited the apoptosis of cardiomyocytes. Through this way, the size of myocardial infarction was significantly reduced after MI/R injury in vivo, better than that of polydatin, suggesting that 17c is a promising cardioprotectant for the prevention of MI/R injury.


Assuntos
Carbolinas/farmacologia , Descoberta de Drogas , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Masculino , Estrutura Molecular , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Superóxido Dismutase/metabolismo
19.
Theriogenology ; 172: 169-177, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174755

RESUMO

Asiatic acid is a natural triterpene found in Centella asiatica that acts as an effective free radical scavenger. Our previous research showed that asiatic acid delayed porcine oocyte ageing in vitro and improved preimplantation embryo development competence in vitro; however, the protective effects of asiatic acid against oxidative stress in porcine oocyte maturation are still unclear. Here, we investigated the effects of asiatic acid on porcine oocyte in vitro maturation (IVM) and subsequent embryonic development competence after parthenogenetic activation (PA) and in vitro fertilization (IVF). The results of the present research showed that 10 µM asiatic acid supplementation did not affect the expansion of cumulus cells or polar body extrusion of porcine oocytes, while asiatic acid application significantly increased the subsequent blastocyst formation rate and quality of porcine PA and IVF embryos. Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces oxidative stress in porcine oocytes. As expected, asiatic acid supplementation not only decreased intracellular ROS levels but also attenuated H2O2-induced intracellular ROS generation. Further analysis revealed that asiatic acid supplementation enhanced intracellular glutathione production, mitochondrial membrane potential, and ATP generation at the end of IVM. In summary, our results reveal that asiatic acid supplementation exerts beneficial effects on porcine oocytes by regulating oxidative stress during the IVM process and could act as a potential antioxidant in porcine oocytes matured in vitro production systems.


Assuntos
Peróxido de Hidrogênio , Técnicas de Maturação in Vitro de Oócitos , Animais , Blastocisto , Suplementos Nutricionais , Desenvolvimento Embrionário , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/metabolismo , Estresse Oxidativo , Triterpenos Pentacíclicos , Espécies Reativas de Oxigênio/metabolismo , Suínos
20.
Photochem Photobiol Sci ; 20(7): 955-965, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34118013

RESUMO

The pandemic created by SARS-CoV-2 has caused a shortage in the supplies of N95 filtering facepiece respirators (FFRs), disposable respirators with at least 95% efficiency to remove non-oily airborne particles, due to increasing cases all over the world. The current article reviewed various possible decontamination methods for FFR reuse including ultraviolet germicidal irradiation (UVGI), hydrogen peroxide vapor (HPV), microwave-generated steam (MGS), hydrogen peroxide gas plasma (HPGP), and 70% or higher ethanol solution. HPV decontamination was effective against bacterial spores (6 log10 reduction of Geobacillus stearothermophilus spores) on FFRs and viruses (> 4 log10 reduction of various types of viruses) on inanimate surfaces, and no degradation of respirator materials and fit has been reported. 70% or higher ethanol decontamination showed high efficacy in inactivation of coronaviruses on inanimate surfaces (> 3.9 log10 reduction) but it was lower on FFRs which filtration efficiency was also decreased. UVGI method had good biocidal efficacy on FFRs (> 3 log10 reduction of H1N1 virus) combined with inexpensive, readily available equipment; however, it was more time-consuming to ensure sufficient reduction in SARS-CoV-2. MGS treatment also provided good viral decontamination on FFRs (> 4 log10 reduction of H1N1 virus) along with less time-intensive process and readily available equipment while inconsistent disinfection on the treated surfaces and deterioration of nose cushion of FFRs were observed. HPGP was a good virucidal system (> 6 log10 reduction of Vesicular stomatitis virus) but filtration efficiency after decontamination was inconsistent. Overall, HPV appeared to be one of the most promising methods based on the high biocidal efficacy on FFRs, preservation of respirator performance after multiple cycles, and no residual chemical toxicity. Nonetheless, equipment cost and time of the HPV process and a suitable operating room need to be considered.


Assuntos
COVID-19 , Descontaminação/métodos , Respiradores N95/microbiologia , Respiradores N95/virologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/efeitos da radiação , COVID-19/epidemiologia , Desinfecção/métodos , Etanol/farmacologia , Humanos , Peróxido de Hidrogênio/farmacologia , Micro-Ondas , Raios Ultravioleta , Vírus/efeitos dos fármacos , Vírus/isolamento & purificação , Vírus/efeitos da radiação
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