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1.
Molecules ; 29(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38731607

RESUMO

The availability of pure individual betalains in sufficient quantities which permit deeper understanding is still a challenge. This study investigates the high-yielding semisynthesis of betaxanthins using betalamic acid from a natural source (Opuntia dillenii), followed by condensation with ʟ-amino acids and further purification. Moreover, the color stability of the four synthesized individual betaxanthins, namely proline (ʟ-ProBX), alanine (ʟ-AlaBX), leucine (ʟ-LeuBX), and phenylalanine (ʟ-PheBX) betaxanthins, was investigated at different pHs. Their relative contribution to free radical scavenging was also scrutinized by TEAC and DPPH. ʟ-AlaBX and ʟ-LeuBx showed a significantly (p < 0.05) higher antioxidant activity, whereas ʟ-ProBX was the most resistant to the hydrolysis of betaxanthin and hence the least susceptible to color change. The color stability was strongly influenced by pH, with the color of ʟ-ProBX, ʟ-LeuBX, and ʟ-AlaBX at pH 6 being more stable, probably due to the easier hydrolysis under acid conditions. The semisynthesis and purification allowed us to have available remarkable quantities of pure individual betaxanthins of Opuntia dillenii for the first time, and to establish their color properties and antioxidant capacity. This study could be a step forward in the development of the best natural food colorant formulation, based on the betalain structure, which is of special interest in food technology.


Assuntos
Betacianinas , Betaxantinas , Opuntia , Betacianinas/química , Betaxantinas/química , Opuntia/química , Antioxidantes/química , Antioxidantes/síntese química , Antioxidantes/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/síntese química , Cor
2.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791498

RESUMO

The post-column reaction method enables the evaluation of the antiradical capacity of individual components in a mixture by separating the components using HPLC and measuring stable free radical (e.g., DPPH●) scavenging that occurs after the chromatography column. The equipment typically consists of two detectors. The first records signals of the analytes leaving the column. The second records radical scavenging by the analytes, which appears as a negative band. The recorded signals are found on two separate chromatograms, which must be combined to interpret the results. In this study, a single DAD detector was used behind the post-column reactor, enabling the simultaneous recording of the analyte bands and negative signals, indicating radical scavenging. The objective of this study was to evaluate the antiradical capacity of key compounds found in two herbal raw materials used in traditional Chinese medicine. Saposhnikovia divaricata roots contain phenolic acids, chromones, and furanocoumarins. Chlorogenic acid, rosmarinic acid, and imperatorin demonstrated strong radical scavenging, while prim-O-glucoslocimifugin showed a weaker response, both in standards and in root extracts. However, scavenging was not observed for cimifugin and 4'-O-ß-D-glucosyl-5-O-methylvisamminol. Astragalus mongholicus roots contain astragalosides I-IV (triterpene saponins). None of these showed DPPH● scavenging. Furthermore, additional signals were observed, indicating the presence of unidentified radical scavenging compounds.


Assuntos
Sequestradores de Radicais Livres , Extratos Vegetais , Plantas Medicinais , Plantas Medicinais/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão/métodos , Sequestradores de Radicais Livres/química , Apiaceae/química , Raízes de Plantas/química , Cromonas/análise , Cromonas/química , Furocumarinas/química , Furocumarinas/análise
3.
J Nanobiotechnology ; 22(1): 252, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750509

RESUMO

With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.


Assuntos
Envelhecimento , Sequestradores de Radicais Livres , Nanoestruturas , Estresse Oxidativo , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Nanoestruturas/química , Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/química
4.
Life Sci ; 348: 122700, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38724004

RESUMO

AIMS: To elucidate the impact of 10-(6-plastoquinonyl) decyltriphenylphosphonium (SkQ1) as an anti-colitogenic agent for maintenance of colon epithelial tract in ulcerated mice through recovery of mitochondrial dysfunction and mitochondrial stress by virtue of its free radical scavenging properties. MAIN METHODS: DSS induced ulcerated BALB/c mice were treated with SkQ1 for 14 days @ 30 nmol/kg/body wt./day/mice. Post-treatment, isolated colonic mitochondria were utilized for spectrophotometric and spectrofluorometric biochemical analysis of various mitochondrial functional variables including individual mitochondrial respiratory enzyme complexes. Confocal microscopy was utilized for measuring mitochondrial membrane potential in vivo. ELISA technique was adapted for measuring colonic nitrite and 3-nitrotyrosine (3-NT) content. Finally in vitro cell line study was carried out to substantiate in vivo findings and elucidate the involvement of free radicals in UC using antioxidant/free radical scavenging regimen. KEY FINDINGS: Treatment with SkQ1 in vivo reduced histopathological severity of colitis, induced recovery of mitochondrial respiratory complex activities and associated functional variables, improved oxidative stress indices and normalized mitochondrial cardiolipin content. Importantly, SkQ1 lowered nitrite concentration and 3-nitrotyrosine formation in vivo. In vitro SkQ1 restored mitochondrial functions wherein the efficacy of SkQ1 proved equal or better compared to SOD and DMSO indicating predominant involvement of O2- and OH in UC. However, NO and ONOO- also seemed to play a secondary role as MEG and L-NAME provided lesser protection as compared to SOD and DMSO. SIGNIFICANCE: SkQ1 can be considered as a potent anti-colitogenic agent by virtue of its free radical scavenging properties in treating UC.


Assuntos
Colite Ulcerativa , Colo , Camundongos Endogâmicos BALB C , Mitocôndrias , Estresse Oxidativo , Plastoquinona , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Plastoquinona/análogos & derivados , Plastoquinona/farmacologia , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/farmacologia , Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sulfato de Dextrana
5.
Chem Biol Interact ; 396: 111034, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38723799

RESUMO

This study aimed to explore the antioxidant and prooxidative activity of two natural furanocoumarin derivatives, Bergaptol (4-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, BER) and Xanthotoxol (9-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, XAN). The collected thermodynamic and kinetic data demonstrate that both compounds possess substantial antiradical activity against HO• and CCl3OO• radicals in physiological conditions. BER exhibited better antiradical activity in comparison to XAN, which can be attributed to the enhanced deprotonation caused by the positioning of the -OH group on the psoralen ring. In contrast to highly reactive radical species, newly formed radical species BER• and XAN• exhibited negligible reactivity towards the chosen constitutive elements of macromolecules (fatty acids, amino acids, nucleobases). Furthermore, in the presence of O2•─, the ability to regenerate newly formed radicals BER• and XAN• was observed. Conversely, in physiological conditions in the presence of Cu(II) ions, both compounds exhibit prooxidative activity. Nevertheless, the prooxidative activity of both compounds is less prominent than their antioxidant activity. Furthermore, it has been demonstrated that anionic species can engage in the creation of a chelate complex, which restricts the reduction of metal ions when reducing agents are present (O2•─ and Asc─). Moreover, studies have demonstrated that these chelating complexes can be coupled with other radical species, hence enhancing their ability to inactivate radicals. Both compounds exhibited substantial inhibitory effects against enzymes involved in the direct or indirect generation of ROS: Xanthine Oxidase (XOD), Lipoxygenase (LOX), Myeloperoxidase (MPO), NADPH oxidase (NOX).


Assuntos
Antioxidantes , Furocumarinas , Furocumarinas/química , Furocumarinas/farmacologia , Cinética , Antioxidantes/química , Antioxidantes/farmacologia , Teoria da Densidade Funcional , Oxirredução , Termodinâmica , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lipoxigenase/metabolismo , Xantina Oxidase/metabolismo , Xantina Oxidase/antagonistas & inibidores , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia
6.
J Nanobiotechnology ; 22(1): 229, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720321

RESUMO

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.


Assuntos
Síndromes do Olho Seco , Soluções Oftálmicas , Espécies Reativas de Oxigênio , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Síndromes do Olho Seco/tratamento farmacológico , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Córnea/efeitos dos fármacos , Córnea/metabolismo , Álcool de Polivinil/química , Humanos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Boratos/química , Nanopartículas/química , Masculino
7.
Sci Rep ; 14(1): 10145, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698070

RESUMO

For centuries, medicinal plants have served as the cornerstone for traditional health care systems and same practice is still prevalent today. In the Himalayan region, Saussurea heteromalla holds a significant place in traditional medicine and is used to address various health issues. Despite its historical use, little exploration has focused on its potential for scavenging free radicals and reducing inflammation. Hence, our current study aims to investigate the free radical scavenging capabilities of S. heteromalla extracts. The n-hexane extract of entire plant revealed promising activity. This extract underwent extensive extraction on a larger scale. Subsequent purification, employing column chromatography, HPLC-DAD techniques, led to the identification of active compounds, confirmed via GC-MS and the NIST database as 1-O-butyl 2-O-octyl benzene-1,2-dicarboxylate and 2,4-ditert-butylphenol. Assessing the free radical scavenging properties involved utilizing RAW-264.7 macrophages activated by lipopolysaccharides. Notably, the compound 2,4-di-tert-butylphenol exhibited remarkable scavenging abilities, demonstrating over 80% inhibition of Nitric oxide. This study stands as the inaugural report on the isolation of these compounds from S. heteromalla.


Assuntos
Antioxidantes , Cromatografia Gasosa-Espectrometria de Massas , Macrófagos , Óxido Nítrico , Extratos Vegetais , Saussurea , Saussurea/química , Camundongos , Óxido Nítrico/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Antioxidantes/farmacologia , Antioxidantes/química , Lipopolissacarídeos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
8.
Int J Biol Macromol ; 269(Pt 1): 131914, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703527

RESUMO

The healing of critical-sized bone defects is a major challenge in the field of bone tissue engineering. Gelatin-related hydrogels have emerged as a potential solution due to their desirable properties. However, their limited osteogenic, mechanical, and reactive oxygen species (ROS)-scavenging capabilities have hindered their clinical application. To overcome this issue, we developed a biofunctional gelatin-Mxene nanocomposite hydrogel. Firstly, we prepared two-dimensional (2D) Ti3C2 MXene nanosheets using a layer delamination method. Secondly, these nanosheets were incorporated into a transglutaminase (TG) enzyme-containing gallic acid-imbedded gelatin (GGA) pre-gel solution to create an injectable GGA-MXene (GM) nanocomposite hydrogel. The GM hydrogels exhibited superior compressive strength (44-75.6 kPa) and modulus (24-44.5 kPa) compared to the GGA hydrogels. Additionally, the GM hydrogel demonstrated the ability to scavenge reactive oxygen species (OH- and DPPH radicals), protecting MC3T3-E1 cells from oxidative stress. GM hydrogels were non-toxic to MC3T3-E1 cells, increased alkaline phosphatase secretion, calcium nodule formation, and upregulated osteogenic gene expressions (ALP, OCN, and RUNX2). The GM400 hydrogel was implanted in critical-sized calvarial defects in rats. Remarkably, it exhibited significant potential for promoting new bone formation. These findings indicated that GM hydrogel could be a viable candidate for future clinical applications in the treatment of critical-sized bone defects.


Assuntos
Gelatina , Hidrogéis , Nanocompostos , Osteogênese , Espécies Reativas de Oxigênio , Crânio , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Gelatina/química , Nanocompostos/química , Osteogênese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Crânio/efeitos dos fármacos , Crânio/patologia , Camundongos , Ratos , Regeneração Óssea/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Titânio/química , Linhagem Celular , Engenharia Tecidual/métodos
9.
Physiol Plant ; 176(3): e14313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666351

RESUMO

Bipolaris setariae is known to cause brown stripe disease in sugarcane, resulting in significant yield losses. Silicon (Si) has the potential to enhance plant growth and biotic resistance. In this study, the impact of Si on brown stripe disease was investigated across susceptible and resistant sugarcane varieties, utilizing four Si concentrations (0, 15, 30, and 45 g per barrel of Na2SiO3·5H2O). Si significantly reduced the incidence of brown stripe disease (7.41-59.23%) and alleviated damage to sugarcane growth parameters, photosynthetic parameters, and photosynthetic pigments. Submicroscopic observations revealed that Si induced the accumulation of silicified cells in leaves, reduced spore accumulation, decreased stomatal size, and protected organelles from B. setariae damage. In addition, Si increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), reduced reactive oxygen species production (malondialdehyde and hydrogen peroxide) and modulated the expression of genes associated with hormone signalling (PR1, TGA, AOS, AOC, LOX, PYL8, and SnRK2), leading to the accumulation of abscisic acid and jasmonic acid and inhibiting SA synthesis. Si also activated the activity of metabolism-related enzymes (polyphenol oxidase and phenylalanine ammonia lyase) and the gene expression of PAL-dependent genes (PAL, C4H, and 4CL), regulating the accumulation of metabolites, such as chlorogenic acid and lignin. The antifungal test showed that chlorogenic acid (15ug µL-1) had a significant inhibitory effect on the growth of B. setariae. This study is the first to demonstrate the inhibitory effect of Si on B. setariae in sugarcane, highlighting Si as a promising and environmentally friendly strategy for managing brown stripe disease.


Assuntos
Doenças das Plantas , Reguladores de Crescimento de Plantas , Espécies Reativas de Oxigênio , Saccharum , Silício , Saccharum/efeitos dos fármacos , Saccharum/metabolismo , Saccharum/microbiologia , Saccharum/genética , Saccharum/crescimento & desenvolvimento , Silício/farmacologia , Silício/metabolismo , Doenças das Plantas/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Folhas de Planta/genética , Ascomicetos/fisiologia , Ascomicetos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo
10.
Sci Rep ; 14(1): 9195, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649707

RESUMO

The development of novel antioxidant compounds with high efficacy and low toxicity is of utmost importance in the medicine and food industries. Moreover, with increasing concerns about the safety of synthetic components, scientists are beginning to search for natural sources of antioxidants, especially essential oils (EOs). The combination of EOs may produce a higher scavenging profile than a single oil due to better chemical diversity in the mixture. Therefore, this exploratory study aims to assess the antioxidant activity of three EOs extracted from Cymbopogon flexuosus, Carum carvi, and Acorus calamus in individual and combined forms using the augmented-simplex design methodology. The in vitro antioxidant assays were performed using DPPH and ABTS radical scavenging approaches. The results of the Chromatography Gas-Mass spectrometry (CG-MS) characterization showed that citral (29.62%) and niral (27.32%) are the main components for C. flexuosus, while D-carvone (62.09%) and D-limonene (29.58%) are the most dominant substances in C. carvi. By contrast, ß-asarone (69.11%) was identified as the principal component of A. calamus (30.2%). The individual EO exhibits variable scavenging activities against ABTS and DPPH radicals. These effects were enhanced through the mixture of the three EOs. The optimal antioxidant formulation consisted of 20% C. flexuosus, 53% C. carvi, and 27% A. calamus for DPPHIC50. Whereas 17% C. flexuosus, 43% C. carvi, and 40% A. calamus is the best combination leading to the highest scavenging activity against ABTS radical. These findings suggest a new research avenue for EOs combinations to be developed as novel natural formulations useful in food and biopharmaceutical products.


Assuntos
Acorus , Antioxidantes , Carum , Cymbopogon , Óleos Voláteis , Extratos Vegetais , Cymbopogon/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antioxidantes/farmacologia , Antioxidantes/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Acorus/química , Carum/química , Cromatografia Gasosa-Espectrometria de Massas , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia
11.
Int J Biol Macromol ; 267(Pt 1): 131472, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599437

RESUMO

Lignin nanoparticles (LNPs) have gained significant attention for their potential as natural antioxidants. This study investigated the effect of various pretreatment methods on the lignin structure and subsequent antioxidant activity of LNPs. Among four pretreated LNPs, hydrothermal LNPs exhibited the highest antioxidant activity, surpassing unpretreated, acid-pretreated and kraft LNPs, with an impressive efficacy of 91.6%. The relationship between LNPs' structure and antioxidant activity was revealed by 2D heteronuclear singular quantum correlation (1H13C HSQC) and 31P nuclear magnetic resonance (NMR). 1H13C HSQC suggested the cleavage of ß-O-4 ether bonds, as well as a decrease in ferulic acid and p-coumaric acid, which directly influenced the antioxidant activity of LNPs. 31P NMR demonstrated a positive correlation between the total hydroxyl group content and the antioxidant activity. Besides, an isothermal kinetic model for scavenging free radicals was established based on Langmuir kinetic model instead of Freundlich model. Moreover, multilayer LNPs, based on layer-by-layer self-assembly, were prepared and exhibited remarkable antioxidant activity of 95.8%. More importantly, when blended with pure cosmetic cream, the multilayer LNPs maintained antioxidant activity of 86.7%. These finding may promote the practical applications of biomolecules, e.g. lignin additives in cosmetics and pharmaceuticals.


Assuntos
Antioxidantes , Lignina , Nanopartículas , Lignina/química , Nanopartículas/química , Antioxidantes/química , Antioxidantes/farmacologia , Ácidos Cumáricos/química , Cinética , Sequestradores de Radicais Livres/química , Propionatos/química
12.
Mar Drugs ; 22(4)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38667796

RESUMO

Palmaria palmata is a viable source of nutrients with bioactive properties. The present study determined the potential role of post-extraction ultrasonication on some compositional features and antioxidant properties of enzymatic/alkaline extracts of P. palmata (EAEP). No significant difference was detected in terms of protein content and recovery, as well as the amino acid composition of the extracts. The nitrogen-to-protein conversion factor of 5 was found to be too high for the seaweed and EAEP. The extracts sonicated by bath for 10 min and not sonicated showed the highest and lowest total phenolic contents (p < 0.05), respectively. The highest radical scavenging and lowest metal-chelating activities were observed for the non-sonicated sample, as evidenced by IC50 values. The extract sonicated by bath for 10 min showed the most favorable in vitro antioxidant properties since its radical scavenging was not significantly different from that of the not-sonicated sample (p > 0.05). In contrast, its metal-chelating activity was significantly higher (p < 0.05). To conclude, post-extraction ultrasonication by an ultrasonic bath for 10 min is recommended to increase phenolic content and improve the antioxidant properties of EAEP.


Assuntos
Antioxidantes , Quelantes , Fenóis , Extratos Vegetais , Rodófitas , Antioxidantes/química , Antioxidantes/isolamento & purificação , Quelantes/química , Algas Comestíveis/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Rodófitas/química , Sonicação
13.
Biomed Pharmacother ; 174: 116540, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579400

RESUMO

Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu2+ were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS. Our results demonstrated that GSNO@PDA@DS were successfully prepared and the modification of DS effectively boosted the cellular uptake of GSNO@PDA@DS. Moreover, GSNO@PDA@DS lowered cellular ROS and elevated intracellular NO, resulting in a decrease of M1 phenotype, inhibition of NF-κB pathway and down-regulation of proinflammatory cytokine tumor necrosis factor-α (TNF-α). Further in vivo studies confirmed that GSNO@PDA@DS significantly relieved symptoms and bone erosion by regulating the microenvironment of RA, highlighting the potential of GSNO@PDA@DS for RA therapy through ROS scavenging and NO-mediated suppression of inflammatory signaling.


Assuntos
Artrite Reumatoide , NF-kappa B , Doadores de Óxido Nítrico , Polímeros , Espécies Reativas de Oxigênio , S-Nitrosoglutationa , Espécies Reativas de Oxigênio/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Animais , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/administração & dosagem , Camundongos , NF-kappa B/metabolismo , S-Nitrosoglutationa/farmacologia , S-Nitrosoglutationa/administração & dosagem , Células RAW 264.7 , Polímeros/química , Indóis/farmacologia , Indóis/administração & dosagem , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/administração & dosagem , Sinergismo Farmacológico , Masculino , Transdução de Sinais/efeitos dos fármacos , Sulfato de Dextrana , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Sistemas de Liberação de Medicamentos/métodos
14.
Int J Biol Macromol ; 266(Pt 2): 131357, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580010

RESUMO

The microenvironment of bone defect site is vital for bone regeneration. Severe bone defect is often accompanied with severe inflammation and elevated generation of reactive oxygen species (ROS) during bone repair. In recent years, the unfriendly local microenvironment has been paid more and more attention. Some bioactive materials with the ability to regulate the microenvironment to promote bone regeneration urgently need to be developed. Here, we develop a multifunctional composite hydrogel composed of photo-responsive methacrylate silk fibroin (SFMA), laponite (LAP) nanocomposite and tannic acid (TA), aiming to endow hydrogel with antioxidant, anti-inflammatory and osteogenic induction ability. Characterization results confirmed that the SFMA-LAP@TA hydrogel could significantly improve the mechanical properties of hydrogel. The ROS-Scavenging ability of the hydrogel enabled bone marrow mesenchymal stem cells (BMSCs) to survive against H2O2-induced oxidative stress. In addition, the SFMA-LAP@TA hydrogel effectively decreased the expression of pro-inflammatory factors in RAW264.7. More importantly, the SFMA-LAP@TA hydrogel could enhance the expression of osteogenic markers of BMSCs under inflammatory condition and greatly promote new bone formation in a critical-sized cranial defect model. Above all, the multifunctional hydrogel could effectively promote bone regeneration in vitro and in vivo by scavenging ROS and reducing inflammation, providing a prospective strategy for bone regeneration.


Assuntos
Regeneração Óssea , Fibroínas , Hidrogéis , Inflamação , Células-Tronco Mesenquimais , Nanocompostos , Osteogênese , Polifenóis , Espécies Reativas de Oxigênio , Taninos , Regeneração Óssea/efeitos dos fármacos , Animais , Fibroínas/química , Fibroínas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Taninos/química , Taninos/farmacologia , Camundongos , Inflamação/tratamento farmacológico , Nanocompostos/química , Hidrogéis/química , Hidrogéis/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células RAW 264.7 , Osteogênese/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
15.
New Phytol ; 242(5): 2043-2058, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38515251

RESUMO

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.


Assuntos
Adaptação Fisiológica , Secas , Regulação da Expressão Gênica de Plantas , Glutationa Transferase , MicroRNAs , Proteínas de Plantas , Populus , Espécies Reativas de Oxigênio , Populus/genética , Populus/fisiologia , Populus/enzimologia , MicroRNAs/genética , MicroRNAs/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Adaptação Fisiológica/genética , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética , Sequestradores de Radicais Livres/metabolismo , Sequência de Bases , Genes de Plantas , Regiões Promotoras Genéticas/genética , Resistência à Seca
16.
Molecules ; 29(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38543039

RESUMO

Yak whey protein concentrates (YWPCs) have good functional properties, but there is still a gap in the study of their peptides. In this study, peptides were obtained by enzymatic hydrolysis, and the bioactivity of each ultrafiltration fraction was evaluated using an optimal process. YWPCs were isolated and purified from yak milk as the raw material. Alkaline protease, trypsin, and papain were used to hydrolyze YWPCs. The protease with the highest degree of hydrolysis (DH) and peptide concentration was selected as the most suitable enzyme. The effects of pH, temperature, time, and the enzyme-to-substrate ratio (E/S) on the DH and peptide concentration were investigated, and response surface methodology was utilized to optimize the hydrolysis process. The hydrolysate was separated using ultrafiltration membranes with molecular weight cut-offs of 10 kDa, 5 kDa, 3 kDa, and 1 kDa. The bioactivity of each ultrafiltration component was analyzed, including the inhibition rates of α-amylase and xanthine oxidase (XOD) activities and the scavenging rates of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radicals. The results indicated that alkaline protease was the best enzyme for hydrolyzing YWPCs. The peptide concentration in the YWPC hydrolysate was the highest (17.21 mg/mL) at a pH of 8 and a concentration of 7500 U/g, after 2.5 h at 62 °C. The enzymatic hydrolysate was ultrafiltered to yield four peptide fractions, of which the <1 kDa peptides exhibited the highest α-amylase inhibitory activity (22.06%), XOD inhibitory activity (17.15%), and ABTS cationic free radical scavenging rate (69.55%). This demonstrates the potential of YWPC hydrolyzed peptides for hypoglycemic, uric acid-lowering, and antioxidant applications, providing a theoretical basis for the high-value utilization of YWPCs.


Assuntos
Antioxidantes , Benzotiazóis , Sequestradores de Radicais Livres , Ácidos Sulfônicos , Animais , Bovinos , Hidrólise , Sequestradores de Radicais Livres/química , Proteínas do Soro do Leite , Antioxidantes/química , Peptídeos/química , Papaína/metabolismo , alfa-Amilases , Hidrolisados de Proteína/química
17.
Int J Med Mushrooms ; 26(3): 67-76, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505904

RESUMO

Five kinds of exopolysaccharides (EPS) were obtained by fermentation of Scleroderma areolatum Ehrenb. with sucrose, glucose, maltose, lactose, and fructose as carbon sources. Antioxidant abilities of the obtained EPSs were evaluated by inhibiting AAPH, HO·, and glutathione (GS·) induced oxidation of DNA and quenching 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS· and galvinoxyl radicals. The effects of carbon sources on the antioxidant properties of EPSs could be examined. The results showed that five EPSs can effectively inhibit radicals induced oxidation of DNA, and the thiobarbituric acid reactive substances (TBARS) percentages were 44.7%-80.8%, 52.3%-77.5%, and 44.7%-73.3% in inhibiting AAPH, HO·, and GS· induced oxidation of DNA, respectively. All five EPSs could scavenge ABTS· and galvinoxyh, and exhibit superior activity in scavenging free radicals. Antioxidant abilities of EPS with fructose as carbon source were highest among five EPS.


Assuntos
Amidinas , Antioxidantes , Basidiomycota , Benzotiazóis , Carbono , Ácidos Sulfônicos , Antioxidantes/farmacologia , Antioxidantes/química , DNA/química , Frutose , Sequestradores de Radicais Livres/farmacologia
18.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474192

RESUMO

The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Feminino , Gravidez , Esclerose Lateral Amiotrófica/tratamento farmacológico , Antioxidantes/uso terapêutico , Antipirina , Edaravone/farmacologia , Edaravone/uso terapêutico , Sequestradores de Radicais Livres/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Placenta
19.
Int J Biol Macromol ; 266(Pt 1): 131106, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552685

RESUMO

The process of diabetic wound healing was influenced by the excessive proliferation of reactive oxygen species (ROS). Therefore, in the process of healing diabetic wounds, it was crucial to removing ROS. This study designed composited nanoparticles: KBP, consisted by Konjac glucomannan, bovine serum albumin, and Prussian blue. Then they were embedded in Konjac glucomannan and hydroxypropyl trimethylammonium chloride chitosan composite hydrogel (KH), The KBP@KH hydrogel finally achieved excellent efficacy in diabetic wound healing. The in vitro and in vivo experiments demonstrated that KPB nanoparticles exhibited favorable ROS scavenging capability and biosafety. The KBP@KH hydrogel not only effectively eliminated ROS from diabetic wounds, but also exhibited excellent wound adaptability. The KBP@KH hydrogel facilitated angiogenesis and suppressed the production of inflammatory factors. Overall, the KBP@KH hydrogel dressing was characterized by its user-friendly nature, safety, and high efficiency.


Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Ferrocianetos , Hidrogéis , Mananas , Nanocompostos , Espécies Reativas de Oxigênio , Soroalbumina Bovina , Cicatrização , Animais , Bovinos , Humanos , Masculino , Camundongos , Ratos , Antioxidantes/farmacologia , Antioxidantes/química , Bandagens , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Ferrocianetos/química , Ferrocianetos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Hidrogéis/química , Hidrogéis/farmacologia , Mananas/química , Mananas/farmacologia , Nanocompostos/química , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/química , Cicatrização/efeitos dos fármacos
20.
Can J Physiol Pharmacol ; 102(6): 361-373, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447123

RESUMO

Coumarins represent a diverse class of natural compounds whose importance in pharmaceutical and agri-food sectors has motivated multiple novel synthetic derivatives with broad applicability. The phenolic moiety in 4-hydroxycoumarins underscores their potential to modulate the equilibrium between free radicals and antioxidant species within biological systems. The aim of this work was to assess the antioxidant activity of 18 4-hydroxycoumarin coumarin derivatives, six of which are commercially available and the other 12 were synthesized and chemically characterized and described herein. The 4-hydroxycoumarins were prepared by a two steps synthetic strategy with satisfactory yields. Their antioxidant potential was evaluated through three in vitro methods, two free radical-scavenging assays (DPPH• and ABTS•+) and a metal chelating activity assay. Six synthetic coumarins (4a, 4g, 4h, 4i, 4k, 4l) had a scavenging capacity of DPPH• higher than butylated hydroxytoluene (BHT) (IC50 = 0.58 mmol/L) and compound 4a (4-hydroxy-6-methoxy-2 H-chromen-2-one) with an IC50 = 0.05 mmol/L outperformed both BHT and ascorbic acid (IC50 = 0.06 mmol/L). Nine hydroxycoumarins had a scavenging capacity against ABTS•+ greater (C3, 4a, 4c) or comparable (C1, C2, C4, C6, 4g, 4l) to Trolox (IC50 = 34.34 µmol/L). Meanwhile, the set had a modest ferrous chelation capacity, but most of them (C2, C5, C6, 4a, 4b, 4h, 4i, 4j, 4k, 4l) reached up to more than 20% chelating ability percentage. Collectively, this research work provides valuable structural insights that may determine the scavenging and metal chelating activity of 4-hydroxycoumarins. Notably, substitutions at the C6 position appeared to enhance scavenging potential, while the introduction of electron-withdrawing groups showed promise in augmenting chelation efficiency.


Assuntos
4-Hidroxicumarinas , Antioxidantes , Sequestradores de Radicais Livres , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/farmacologia , 4-Hidroxicumarinas/síntese química , Antioxidantes/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Picratos/química , Quelantes/química , Quelantes/farmacologia , Quelantes/síntese química , Compostos de Bifenilo/química , Ácidos Sulfônicos/química , Relação Estrutura-Atividade , Benzotiazóis
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