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1.
Eur Rev Med Pharmacol Sci ; 24(16): 8585-8591, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32894566

RESUMO

Some surface proteins of the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can bind to the hemoglobin molecule of an erythrocyte, which leads to the destruction of the structure of the heme and the release of harmful iron ions to the bloodstream. The degradation of hemoglobin results in the impairment of oxygen-carrying capacity of the blood, and the accumulation of free iron enhances the production of reactive oxygen species. Both events can lead to the development of oxidative stress. In this case, oxidative damage to the lungs leads then to the injuries of all other tissues and organs. The use of uridine, which preserves the structure of pulmonary alveoli and the air-blood barrier of the lungs in the course of experimental severe hypoxia, and dihydroquercetin, an effective free radical scavenger, is promising for the treatment of COVID-19. These drugs can also be used for the recovery of the body after the severe disease.


Assuntos
Infecções por Coronavirus/patologia , Estresse Oxidativo , Pneumonia Viral/patologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Eritrócitos/citologia , Eritrócitos/metabolismo , Eritrócitos/virologia , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/uso terapêutico , Hemoglobinas/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/fisiologia , Quercetina/análogos & derivados , Quercetina/farmacologia , Quercetina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Uridina/farmacologia , Uridina/uso terapêutico
2.
Gene ; 762: 145042, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777529

RESUMO

OBJECTIVES: Inhibitory effect of allicin with broad-spectrum antimicrobial activity on A. fumigatus and the regulation mechanism of inflammation and autophagy in vitro and in vivo. METHODS: The corresponding concentration of allicin was prepared according to the needs of the experiment. In vitro, 2 ml 5 × 104 of fungal spores suspension was added to the 6-well plate per hole, and different final concentrations of allicin (1 µl/ml, 2.5 µl/ml, 5 µl/ml, 10 µl/ml, 20 µl/ml, 30 µl/ml) were added. The fungal spores were stained by fluorescent dye SYTO 9 (green) every day, and the spore germination inhibition was detected by flow cytometry in different PH. RAW264.7 cells were cultured and stimulated by A. fumigatus spores for 3 h, then allicin solution was added. Then some cells were stained with ROS probe (green) and hochest33342 (blue). The effect of allicin on ROS was observed by fluorescence microscope. The other part of cells extracted protein from cell lysate and detected the effect of allicin on inflammatory factors and autophagy by Western-blotting. The green and red spots of RAW264.7 cells stably transfected with GFP-RFP-LC3 were observed by fluorescence microscopy. In vivo, A. fumigatus spore was injected intratracheally into mice, then allicin was injected intravenously at a concentration of 5 mg/kg/day for 7 consecutive days. The survival status, pulmonary fungal load and weight of mice was recorded continuously for 30 days and detected the changes of lung by pathological examination and immunohistochemistry. RESULTS: In vitro, allicin significantly inhibited the spore germination of A. fumigatus within 24 h in a dose-dependent manner and it had a stable inhibition on the spore germination of A. fumigatus in acidic environment. Cell experiments showed that allicin inhibited intracellular spore germination by inhibiting ROS production, inflammation and autophagy. In the animal experiment, the survival rate and body weight of allicin injection group were higher than that of non injection group, while the spore load of lung was lower than that of non injection group (P < 0.05). CONCLUSIONS: These results support that allicin reduces inflammation and autophagy resistance to A. fumigatus infection, It also provides a possible treatment for Aspergillus infectious diseases, i.e. early anti-inflammation, antibiotics or drugs that inhibit excessive autophagy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aspergilose/tratamento farmacológico , Autofagia , Depuradores de Radicais Livres/uso terapêutico , Ácidos Sulfínicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Aspergillus fumigatus/patogenicidade , Aspergillus fumigatus/fisiologia , Feminino , Depuradores de Radicais Livres/farmacologia , Pulmão/metabolismo , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Esporos Fúngicos/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia
3.
Life Sci ; 259: 118287, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32814066

RESUMO

Alzheimer's disease (AD) is a fatal neurodegenerative disease that requires immediate attention. Oxidative stress that leads to the generation of reactive oxygen species is a contributing factor to the disease progression by promoting synthesis and deposition of amyloid-ß, the main hallmark protein in AD. It has been previously demonstrated that nanoyttria possesses antioxidant properties and can alleviate cellular oxidative injury in various toxicity and disease models. This review proposed that nanoyttria could be used for the treatment of AD. In this paper, the evidence on the antioxidant potential of nanoyttria is presented and its prospects on AD therapy are discussed.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Depuradores de Radicais Livres/farmacologia , Nanopartículas/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Ítrio/uso terapêutico , Doença de Alzheimer/metabolismo , Animais , Humanos , Ratos , Ítrio/administração & dosagem
4.
Toxicol Lett ; 332: 118-129, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659471

RESUMO

Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS). In this study, we have verified ROS generation in silver-treated bronchial epithelial cells prompting evaluation of three antioxidants, N-acetyl cysteine (NAC), ascorbic acid, and melatonin, to identify potential prophylactic agents. Among them, NAC was the only candidate that abrogated the ROS generation in response to silver acetate exposure resulting in the rescue of these cells from silver-associated toxicity. Further, this protective effect directly translated to preservation of metabolic activity, as demonstrated by the normal levels of citric acid cycle metabolites in NAC-pretreated silver acetate-exposed cells. Because the citric acid cycle remained functional, silver-exposed cells pre-incubated with NAC demonstrated significantly higher levels of adenosine triphosphate levels compared with NAC-free controls. Moreover, we found that this prodigious capacity of NAC to rescue silver acetate-exposed cells was due not only to its antioxidant activity, but also to its ability to directly bind silver. Despite binding to silver, NAC did not alter the antimicrobial activity of silver acetate.


Assuntos
Acetilcisteína/farmacologia , Antibacterianos/farmacologia , Depuradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Prata/toxicidade , Acetatos/farmacologia , Trifosfato de Adenosina/metabolismo , Ácido Ascórbico/farmacologia , Linhagem Celular , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Humanos , Melatonina/farmacologia , Testes de Sensibilidade Microbiana , Compostos de Prata/farmacologia , Superóxidos/metabolismo
5.
PLoS One ; 15(6): e0234157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516332

RESUMO

Brazilian native fruits are a rich source of polyphenolic compounds that can act as anti-inflammatory and antioxidant agents. Here, we determined the polyphenolic composition, anti-inflammatory mechanism of action, antioxidant activity and systemic toxicity in Galleria mellonella larvae of Eugenia selloi B.D.Jacks. (synonym Eugenia neonitida Sobral) extract (Ese) and its polyphenol-rich fraction (F3) obtained through bioassay-guided fractionation. Phenolic compounds present in Ese and F3 were identified by LC-ESI-QTOF-MS. The anti-inflammatory activity of Ese and F3 was tested in vitro and in vivo through NF-κB activation, cytokine release and neutrophil migration assays. The samples were tested for their effects against reactive species (ROO•, O2•-, HOCl and NO•) and for their toxicity in Galleria mellonella larvae model. The presence of hydroxybenzoic acid, ellagitannins and flavonoids was identified. Ese and F3 reduced NF-κB activation, cytokine release and neutrophil migration, with F3 being three-fold more potent. Overall, F3 exhibited strong antioxidant effects against biologically relevant radicals, and neither Ese nor F3 were toxic to G. mellonella larvae. In conclusion, Ese and F3 revealed the presence of phenolic compounds that decreased the inflammatory parameters evaluated and inhibited reactive oxygen/nitrogen species. E. selloi is a novel source of bioactive compounds that may provide benefits for human health.


Assuntos
Eugenia/química , Frutas/química , Polifenóis/química , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL2/metabolismo , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Lepidópteros/efeitos dos fármacos , Masculino , Camundongos , NF-kappa B/metabolismo , Polifenóis/toxicidade , Células RAW 264.7 , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Food Chem ; 331: 127360, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32585548

RESUMO

The influence of food components on nanoparticle (NP) internalization indicates a need to investigate the behaviors of NPs in a complex system. This study measured the changes of TiO2 NP colloidal stability and quenching of anthocyanin fluorescence to indicate NP-anthocyanin interactions, and cytotoxicity, oxidative stress, expression of ABC transporters and intracellular Ti concentrations in 3D Caco-2 spheroids co-exposed to NPs and anthocyanins to indicate the influence of anthocyanins on NP bio-effects. The anthocyanins were observed to have minimal impacts on colloidal properties of TiO2 NPs. Meanwhile, NP-anthocyanin co-exposure did not induce cytotoxicity or oxidative stress. The fluorescence quenching study indicated the binding of anthocyanins onto TiO2 NPs, and the binding affinity was inversely correlated with NP internalization into 3D Caco-2 spheroids. This may be partially related with the up-regulation of ABC transporters. Our results may provide novel insights into understanding the interactions of NPs and anthocyanins with human intestinal cells.


Assuntos
Antocianinas/farmacologia , Nanopartículas Metálicas/química , Titânio/farmacocinética , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antocianinas/química , Células CACO-2 , Coloides/farmacocinética , Depuradores de Radicais Livres/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Titânio/química
7.
Toxicology ; 440: 152441, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32433928

RESUMO

4-Aminobiphenyl (4-ABP), a well-known human carcinogen, has been shown to cause oxidative DNA damage and induce miR-630 expression in HepG2 cells treated with 18.75 µM-300 µM for 24 h. However, the underlying mechanism regarding the epigenetic regulation of miR-630 on DNA damage repair in liver cells is still not understood and needs to be investigated. In present study, our results showed that miR-630 was upregulated, resulting in mediating a decrease of DNA homologous recombination (HR) repair in L-02, HepG2 or Hep3B cells. Results from a luciferase reporting experiment showed that RAD18 and MCM8 were the potential targets of miR-630 during DNA damage induction. The downregulation of RAD18 or MCM8 by miR-630 was accompanied by inhibition of HR repair. Conversely, inhibiting miR-630 enhanced the expression of RAD18 and MCM8, and rescued HR repair. Additionally, we proved that the transcription factor CREB was related to miR-630 biogenesis in liver cells. Moreover, the levels of CREB, miR-630 expression, and double-strand breaks (DSBs) were attenuated by 5 mM N-acetyl-L-cysteine (NAC) pretreatment, indicating that reactive oxygen species (ROS)-dependent CREB-miR-630 was involved in DSB repair. These findings indicated that the ROS/CREB/-miR-630 axis plays a relevant role in the regulation of RAD18 and MCM8 in HR repair, which may facilitate our understanding of molecular mechanisms regarding the role of miR-630 downregulating DNA damage repair in liver cells.


Assuntos
Compostos de Aminobifenil/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Fígado/metabolismo , MicroRNAs/metabolismo , Proteínas de Manutenção de Minicromossomo/antagonistas & inibidores , Reparo de DNA por Recombinação/efeitos dos fármacos , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Acetilcisteína/farmacologia , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Depuradores de Radicais Livres/farmacologia , Recombinação Homóloga , Humanos , Fígado/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
8.
PLoS One ; 15(4): e0232224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343717

RESUMO

The Amazon region is rich in genetic resources such as oilseeds which have potentially important local commercial exploitation. Despite its high concentration of bioactive compounds, cacay (Caryodendron orinocense Karst.) oil is poorly investigated and explored. Thus, this study focuses on the physicochemical characterization (moisture, density, and saponification, iodine, and acidity values), fatty acid composition as determined by gas chromatograph mass spectrometry (GC/MS), total phenolic content (TPC), and antioxidant activity (DPPH and ABTS radical scavenging assay) of cacay oil, coconut oil and a coconut/cacay oil blend, also known as cacay butter. The antibacterial activity of cacay oil was additionally evaluated. Our study demonstrated that cacay oil presents a high amount of polyunsaturated fatty acid (PUFA) (58.3%) with an emphasis on linoleic acid and a lower acidity value (2.67 ± 0.01 cg I2/g) than butter and coconut oil, indicating a low concentration of free fatty acids. In contrast, cacay butter and coconut oil presented higher saturated fatty acid percentages (69.1% and 78.4%, respectively) and higher saponification values (242.78 and 252.22 mg KOH/g, respectively). The samples showed low moisture and relative density between 912 and 916 kg/m3. The hydrophilic fraction of cacay oil was highlighted in the quantification of TPC (326.27 ± 6.79 mg GAE/kg) and antioxidant capacity in vitro by DPPH radical scavenging assay (156.57 ± 2.25 µmol TE/g). Cacay oil inhibited the growth of Bacillus cereus (44.99 ± 7.68%), Enterococcus faecalis (27.76 ± 0.00%), and Staphylococcus aureus (11.81 ± 3.75%). At long last, this is the first study reporting the physicochemical characterization and bioactive properties of cacay butter. Coconut oil and cacay butter showed great oxidative stability potential due to higher contents of saturated fatty acids. Moreover, cacay oil presents as an alternative source of raw materials for cosmetic and biotechnology industries due to its high concentration of PUFA and for being a rich source of phenolic compounds.


Assuntos
Óleo de Coco/química , Euphorbiaceae/química , Óleos Vegetais/química , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Fenômenos Químicos , Óleo de Coco/farmacologia , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Óleos Vegetais/farmacologia
9.
Acta Cir Bras ; 35(2): e202000203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348402

RESUMO

Purpose To evaluate the effect of remote ischemic conditioning associated to N-acetylcysteine (NAC) on testicular ischemia∕reperfusion (I∕R) injury in rats. Methods Twenty-five adult male Wistar rats were randomly distributed into five experimental groups (n=5), as follows: Sham, I∕R, Perconditioning (PER), NAC and PER+NAC. Two-hour ischemia was induced by rotating the left testis 720° to clockwise direction, followed by 4 hours of reperfusion. Perconditioning was performed by three I/R cycles of 10 min each on the left limb, 30 min before reperfusion. N-acetylcysteine (150 mg∕kg) was administered 30 min before reperfusion. Results Statistical differences were observed in MDA levels between I/R group with all groups (p<0.01), in addition there was statistical difference between PER and Sham, and PER+ NAC groups (p<0.05) in plasma. Conclusions The protective effect of perconditioning isolated in the reduction of lipid peroxidation related to oxidative stress was demonstrated. However, when Perconditioning was associated with NAC, there was no protective effect against testicular injury of ischemia and reperfusion.


Assuntos
Acetilcisteína/farmacologia , Depuradores de Radicais Livres/farmacologia , Precondicionamento Isquêmico/métodos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão , Testículo/irrigação sanguínea , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Capacidade de Absorbância de Radicais de Oxigênio , Distribuição Aleatória , Ratos , Ratos Wistar , Testículo/efeitos dos fármacos
10.
J Appl Microbiol ; 129(2): 296-310, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32145138

RESUMO

AIMS: A multidisciplinary approach was used to compare phenolic composition, radical scavenging and antimicrobial activity of propolis samples from different geographical localities, and plant resin against various microorganisms. METHODS AND RESULTS: Using UHPLC-qqqMS quantitative analysis, 28 phenolic compounds were determined. Caffeic and p-coumaric acids were identified as main phenolic acids in poplar propolis samples, except samples from Russia (P6) and China (P7). Radical scavenging activity (applying DPPH spectrophotometric assay) showed the highest activity of Serbian (40·51%) and Chinese (53·21%) propolis samples. Broth microdilution method was used for the oral cavity, fungal phytopathogenic and human vaginal isolates which have been identified at a molecular level. The most sensitive bacterial isolates were Lactobacillus acidophilus (MIC of 0·03-0·13 mg ml-1 ) and the oral streptococci isolates (MIC values of 0·19-0·13 mg ml-1 ). The most sensitive fungal phytopathogenic isolate was Fusarium oxysporum (MIC 0·003 mg ml-1 ). All samples, except propolis from Serbia (P4) and Turkey (P5), showed a strong antifungal activity against Fusarium sporotrichioides, Fusarium subglutinans and Fusarium proliferatum. CONCLUSION: The results of various tests indicate good radical scavenging and antimicrobial activity against important human and plant pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: A detailed propolis analysis is important when proposing a preparation of new biological antimicrobial products which have a positive impact on human health and reduce antibacterial resistance.


Assuntos
Anti-Infecciosos/farmacologia , Depuradores de Radicais Livres/farmacologia , Fenóis/análise , Populus/química , Própole/química , Anti-Infecciosos/análise , Feminino , Depuradores de Radicais Livres/análise , Fusarium/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Microbiota/efeitos dos fármacos , Boca/microbiologia , Fenóis/farmacologia , Própole/farmacologia , Vagina/microbiologia
11.
Einstein (Sao Paulo) ; 18: eAO5022, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32215468

RESUMO

OBJECTIVE: To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. METHODS: Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. RESULTS: Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. CONCLUSION: Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.


Assuntos
Acetilcisteína/farmacologia , Dieta Hiperlipídica , Depuradores de Radicais Livres/farmacologia , Resistência à Insulina/fisiologia , Miocárdio/metabolismo , Obesidade/metabolismo , Estresse Oxidativo/fisiologia , Animais , Glicemia/análise , Western Blotting , Peso Corporal , Fluoresceínas/análise , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Espécies Reativas de Oxigênio/análise , Valores de Referência , Espectrofotometria
12.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 47-52, Jan.-Mar. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1090559

RESUMO

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.


Assuntos
Animais , Masculino , Acetilcisteína/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Cisplatino/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Antineoplásicos/toxicidade , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Microscopia Eletrônica de Varredura , Potenciais Evocados Auditivos do Tronco Encefálico , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Imunofluorescência , Cisplatino/uso terapêutico , Ratos Wistar , Cóclea/anatomia & histologia , Cóclea/efeitos dos fármacos , Radicais Livres , Glutationa Peroxidase/metabolismo , Perda Auditiva Neurossensorial/prevenção & controle
13.
Int J Nanomedicine ; 15: 1349-1361, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184590

RESUMO

Background: Impaired wound healing might be associated with many issues, especially overactive of reactive oxygen species (ROS), deficiency of blood vessels and immature of epidermis. N-acetylcysteine (NAC), as an antioxidant, could solve these problems by inhibiting overreactive of ROS, promoting revascularization and accelerating re-epithelialization. How to deliver NAC in situ with a controllable releasing speed still remain a challenge. Materials and Methods: In this study, we combined collagen (Col) with N-acetylcysteine to perform the characteristics of sustained release and chemically crosslinked Col/NAC composite with polyamide (PA) nanofibers to enhance the mechanical property of collagen and fabricated this multi-layered scaffold (PA-Col/NAC scaffold). The physical properties of the scaffolds such as surface characteristics, water absorption and tensile modulus were tested. Meanwhile, the ability to promote wound healing in vitro and in vivo were investigated. Results: These scaffolds were porous and performed great water absorption. The PA-Col/NAC scaffold could sustainably release NAC for at least 14 days. After cell implantation, PA-Col/NAC scaffold showed better cell proliferation and cell migration than the other groups. In vivo, PA-Col/NAC scaffolds could promote wound healing best among all the groups. Conclusion: The multi-layered scaffolds could obviously accelerate the process of wound healing and exert better and prolonged effects.


Assuntos
Acetilcisteína/farmacologia , Colágeno/química , Depuradores de Radicais Livres/farmacologia , Nylons/química , Reepitelização/efeitos dos fármacos , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Preparações de Ação Retardada , Masculino , Nanofibras/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
14.
J Fluoresc ; 30(2): 407-418, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32088852

RESUMO

The combination of an Ayurvedic wisdom and nanotechnology may help us to resolve the complex healthcare challenges. A facile and economical one-pot hydrothermal synthesis method has been adopted for preparing a blue fluorescent carbon dots (CDs) with a quantum yield of 15.10% from an Ayurvedic medicinal plant Andrographis paniculata (AP). The Andrographis paniculata derived CDs (AAPCDs) were then characterized using different techniques. Through High Performance Thin Layer Chromatography (HPTLC) profiling of the AP extract and the CDs, it was found that some of the phytoconstituents are retained as such while others may have been converted into their derivatives during the process of formation of CDs. The CDs are designed to possess cellular imaging of human breast carcinoma cells (MCF-7), apart from free radicals sensing and scavenging capabilities. AAPCDs showed minimal cytotoxicity in Multi Drug Resistant clinically isolated strains of gram positive and gram negative bacteria which may be employed for microbiology oriented experiments. These results suggest potential of multi-functional AAPCDs as nano-probes for various pharmaceutical, biomedical and bioengineering applications.


Assuntos
Andrographis/química , Antibacterianos/química , Corantes Fluorescentes/química , Depuradores de Radicais Livres/química , Imagem Óptica , Antibacterianos/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Carbono/química , Sobrevivência Celular/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Corantes Fluorescentes/farmacologia , Depuradores de Radicais Livres/farmacologia , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Células MCF-7 , Medicina Ayurvédica , Testes de Sensibilidade Microbiana , Nanotecnologia , Tamanho da Partícula , Picratos/antagonistas & inibidores , Folhas de Planta/química , Pontos Quânticos/química , Espectrometria de Fluorescência , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície
15.
Am J Respir Cell Mol Biol ; 62(6): 732-746, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32048876

RESUMO

Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCß and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCß mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKCß inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O2- or mitoROS prevented enhanced PKCß-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKCß/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoKATP or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKCß acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKCß/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKCß mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoKATP, and subsequent mitoROS generation.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Mitocôndrias/fisiologia , Proteína Quinase C beta/fisiologia , Artéria Pulmonar/fisiopatologia , Vasoconstrição/fisiologia , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Células Cultivadas , Óxidos N-Cíclicos/farmacologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/metabolismo , Depuradores de Radicais Livres/farmacologia , Humanos , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Hipóxia/enzimologia , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/enzimologia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Canais de Potássio/metabolismo , Mapeamento de Interação de Proteínas , Artéria Pulmonar/enzimologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Síndromes da Apneia do Sono/fisiopatologia , Marcadores de Spin , Acetato de Tetradecanoilforbol/farmacologia
16.
Molecules ; 25(2)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963288

RESUMO

Non-enzymatic browning reactions between lipid aldehydes and aminophospholipids might play an important role in the oxidative stability of cold-pressed vegetable oils. We, therefore, aimed to study the Maillard-type reaction between hexanal, a lipid oxidation product of linoleic acid, and phosphatidylethanolamine (PE (16:0/18:1)) at a ratio of 2:1 at conditions representative of the extraction of cold-pressed soybean oils (CPSBO) and determine the radical scavenging activity of the carbonyl-amine adducts with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The reaction product, 2-pentyl-3,5-dibutyl-dihydropyridine, could be identified by means of LC-ESI-QTOF-MS/MS. The formation of this nitrogen-containing heterocycle significantly increased with time and temperature (p < 0.05). The products formed during the carbonyl-amine reaction between PE (16:0/18:1) and hexanal at 60 °C showed a radical scavenging activity of approximately 20% (p < 0.05). The fraction, containing 2-pentyl-3,5-dibutyl-dihydropyridine, contributed to, but was not solely responsible for, the radical scavenging activity (p < 0.05). Incubation of CPSBO fortified with PE (16:0/18:1) at 60 °C for 60 min had the strongest radical scavenging activity of 85.1 ± 0.62%. Besides 2-pentyl-3,5-dibutyl-dihydropyridine, other carbonyl-amine adducts might impact the radical scavenging activity of CPSBO as well. The oxidative stability of CPSBO might be increased by promoting the formation of carbonyl-amine reaction products, such as 2-pentyl-3,5-dibutyl-dihydropyridine.


Assuntos
Aminas/química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Fosfatidiletanolaminas/química , Óleo de Soja/química , Aldeídos/química , Cromatografia Líquida , Metabolismo dos Lipídeos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oxirredução , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
17.
Appl Biochem Biotechnol ; 190(2): 391-409, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31363982

RESUMO

Microorganisms that survive in the high salt environment have been shown to be a potential source for metabolites with pharmaceutical importance. In the present study, we have investigated the effect of 5 and 10% (w/v) NaCl on growth, biochemical changes, and metabolite production in seven moderately halophilic bacteria isolated from the salterns/mangrove area of South India. Metabolite production by Bacillus VITPS3 increased by 3.18-fold in the presence of 10% (w/v) NaCl concentration. Total phenolic and flavonoid content increased in Bacillus VITPS5 (11.3-fold) and Planococcus maritimus VITP21 (5.99-fold) whereas ß-carotene content was less at higher NaCl concentrations. VITP21 and VITPS5, in response to NaCl, produced metabolites with higher (6.72- and 4.91-fold) DPPH and ABTS radical scavenging activity. UV/visible spectrophotometry of the extracts confirmed the presence of flavonoids, phenolics, and related compounds. 1H-NMR spectra indicated substantial changes in the metabolite production in response to salt concentration. Principal component analysis (PCA) revealed that VITP21 extracts exhibited the highest antioxidant activity compared with other extracts. The present study presents the first report on the comparative analysis of pigment production by moderate halophilic bacteria, in response to the effect of salt and their relation to radical scavenging property.


Assuntos
Antioxidantes/farmacologia , Bacillus/efeitos dos fármacos , Pigmentos Biológicos/biossíntese , Planococcus (Bactéria)/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Bacillus/crescimento & desenvolvimento , Bacillus/metabolismo , Compostos de Bifenilo/metabolismo , Depuradores de Radicais Livres/farmacologia , Picratos/metabolismo , Planococcus (Bactéria)/crescimento & desenvolvimento , Planococcus (Bactéria)/metabolismo
18.
Environ Sci Pollut Res Int ; 27(2): 2155-2164, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31773523

RESUMO

The present study deals with the synthesis of silver nanoparticles (AgNPs) from Rhynchosia rufescens and to evaluate its cytotoxic effect mediated through induced apoptosis. The reduction and capping of phytoconstituents was confirmed using FTIR demonstrating O-H and C-H stretching at different peaks. The size and the shape of the particle were determined using scanning electron microscopy (SEM) illustrating 1 µm to 100 nm in size and the composition of compounds in the AgNPs were revealed using XRD and EDX. The results of the antioxidant assays revealed that the synthesized AgNPs had significant radical scavenging potential in dose-dependent inhibition with 22-64% for DPPH and 25-41% for ferric reducing antioxidant power assay at the concentrations of 20-100 µg/ml. Further, the synthesized AgNPs demonstrated potent cytotoxic activity against human breast cancer (MCF-7) cell line with an IC50 value of 26 ± 1.0 µg/ml by the MTT assay. Cytotoxicity was confirmed using AO/EtBr and DAPI staining method where nuclear condensation and fragmentation of cancer cells was observed after treatment with nanoparticle. The results were further confirmed by flow cytometry analysis which revealed the occurrence of apoptosis during the S phase in cell cycle exposing the potential of the AgNPs against MCF-7 cancer cell. From the results, we conclude that the synthesized AgNPs from Rhynchosia rufescens exhibited multifunctional properties. Graphical abstract.


Assuntos
Apoptose , Fabaceae , Depuradores de Radicais Livres/farmacologia , Nanopartículas Metálicas , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Humanos , Células MCF-7
19.
Nat Prod Res ; 34(6): 872-875, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30345814

RESUMO

Raspberry, the fruit of Rubus Chingji Hu, is a widely distributed economic staple food in China. It has long been used as a traditional medicine in mainland China to treat kidney enuresis, nocturnal emission and premature ejaculation in clinic. In this paper, six known compounds (1 - 6) were purified from the fruits of Rubus chingji. Their structures were elucidated as (16α)-16,17-dihydroxy-ent-kauran-2-one17-O-ß-D-glucopyranoside (1), (16R) -16,17-dihydroxy-ent-kaurane-2-one (2), 3,3'-di-O-methylellagic acid 4-(5''-acetyl)-α-L-arabinofuranoside (3), quercilicoside A (4), esculetine (5) and ethyl-ß-D-glucoside (6). All the compounds were isolated from Rubus Chingji Hu for the first time. Compounds 3 and 5 shown distinctive free radical scavenging activities in DPPH and FRAP assays. In addition, no cytotoxicity was observed for compounds 3 and 5 against different cancer cells, suggesting that they might be useful as potential antioxidant agents against various reactive oxygen species.[Formula: see text].


Assuntos
Antioxidantes/isolamento & purificação , Frutas/química , Rubus/química , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , China , Ácido Elágico/análogos & derivados , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Humanos , Extratos Vegetais/química
20.
Nat Prod Res ; 34(7): 943-949, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30760039

RESUMO

Saussurea involucrata, known for the abundant bioactive components, is a precious traditional Chinese medicine. In this study, a novel guaiane sesquiterpenoid glycoside named (1R, 5R, 6R, 7R, 8S, 11S)-11, 13-dihydrodehydrocostuslactone-8-O-6'-2''(E)-butenoyl-ß-D-glucopyranoside (1), together with seven known compounds (2-8) were isolated from the dried aerial part of S. involucrata. Their structures were elucidated by spectroscopic and physico-chemical analyses. The antioxidant and anti-inflammatory activities of compound 1 were investigated. And compound 1 showed weak radical scavenging activity and low inhibitory activity on nitric oxide (NO) production.


Assuntos
Glicosídeos/isolamento & purificação , Medicina Tradicional Chinesa , Saussurea/química , Sesquiterpenos/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia
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