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1.
Sci Rep ; 14(1): 10145, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698070

RESUMEN

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.


Asunto(s)
Antioxidantes , Cromatografía de Gases y Espectrometría de Masas , Macrófagos , Óxido Nítrico , Extractos Vegetales , Saussurea , Saussurea/química , Ratones , Óxido Nítrico/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células RAW 264.7 , Antioxidantes/farmacología , Antioxidantes/química , Lipopolisacáridos/farmacología , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química
2.
Biomed Pharmacother ; 174: 116540, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38579400

RESUMEN

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.


Asunto(s)
Artritis Reumatoide , FN-kappa B , Donantes de Óxido Nítrico , Polímeros , Especies Reactivas de Oxígeno , S-Nitrosoglutatión , Especies Reactivas de Oxígeno/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Animales , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/administración & dosificación , Ratones , FN-kappa B/metabolismo , S-Nitrosoglutatión/farmacología , S-Nitrosoglutatión/administración & dosificación , Células RAW 264.7 , Polímeros/química , Indoles/farmacología , Indoles/administración & dosificación , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/administración & dosificación , Sinergismo Farmacológico , Masculino , Transducción de Señal/efectos de los fármacos , Sulfato de Dextran , Factor de Necrosis Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Sistemas de Liberación de Medicamentos/métodos
3.
Int J Biol Macromol ; 266(Pt 2): 131357, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580010

RESUMEN

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.


Asunto(s)
Regeneración Ósea , Fibroínas , Hidrogeles , Inflamación , Células Madre Mesenquimatosas , Nanocompuestos , Osteogénesis , Polifenoles , Especies Reactivas de Oxígeno , Taninos , Regeneración Ósea/efectos de los fármacos , Animales , Fibroínas/química , Fibroínas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Taninos/química , Taninos/farmacología , Ratones , Inflamación/tratamiento farmacológico , Nanocompuestos/química , Hidrogeles/química , Hidrogeles/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células RAW 264.7 , Osteogénesis/efectos de los fármacos , Metacrilatos/química , Metacrilatos/farmacología , Ratas , Estrés Oxidativo/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química
4.
Physiol Plant ; 176(3): e14313, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38666351

RESUMEN

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.


Asunto(s)
Enfermedades de las Plantas , Reguladores del Crecimiento de las Plantas , Especies Reactivas de Oxígeno , Saccharum , Silicio , Saccharum/efectos de los fármacos , Saccharum/metabolismo , Saccharum/microbiología , Saccharum/genética , Saccharum/crecimiento & desarrollo , Silicio/farmacología , Silicio/metabolismo , Enfermedades de las Plantas/microbiología , Especies Reactivas de Oxígeno/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Antifúngicos/farmacología , Antifúngicos/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/microbiología , Hojas de la Planta/genética , Ascomicetos/fisiología , Ascomicetos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Depuradores de Radicales Libres/metabolismo
5.
Sci Rep ; 14(1): 9195, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649707

RESUMEN

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.


Asunto(s)
Acorus , Antioxidantes , Carum , Cymbopogon , Aceites Volátiles , Extractos Vegetales , Cymbopogon/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Acorus/química , Carum/química , Cromatografía de Gases y Espectrometría de Masas , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología
6.
Can J Physiol Pharmacol ; 102(6): 361-373, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447123

RESUMEN

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.


Asunto(s)
4-Hidroxicumarinas , Antioxidantes , Depuradores de Radicales Libres , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/farmacología , 4-Hidroxicumarinas/síntesis química , Antioxidantes/síntesis química , Antioxidantes/farmacología , Antioxidantes/química , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Picratos/química , Quelantes/química , Quelantes/farmacología , Quelantes/síntesis química , Compuestos de Bifenilo/química , Ácidos Sulfónicos/química , Relación Estructura-Actividad , Benzotiazoles
7.
J Control Release ; 369: 573-590, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554773

RESUMEN

Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6+ macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6+ macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect-cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.


Asunto(s)
Factor de Transcripción GATA6 , Ácido Hialurónico , Hidrogeles , Macrófagos , Complicaciones Posoperatorias , Especies Reactivas de Oxígeno , Adherencias Tisulares/prevención & control , Animales , Hidrogeles/química , Hidrogeles/administración & dosificación , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ácido Hialurónico/química , Complicaciones Posoperatorias/prevención & control , Factor de Transcripción GATA6/metabolismo , Catequina/análogos & derivados , Catequina/química , Catequina/administración & dosificación , Catequina/farmacología , Ratas Sprague-Dawley , Ratones , Adipatos/química , Masculino , Abdomen/cirugía , Células RAW 264.7 , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Liberación de Fármacos
8.
Molecules ; 29(6)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38543039

RESUMEN

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.


Asunto(s)
Antioxidantes , Benzotiazoles , Depuradores de Radicales Libres , Ácidos Sulfónicos , Animales , Bovinos , Hidrólisis , Depuradores de Radicales Libres/química , Proteína de Suero de Leche , Antioxidantes/química , Péptidos/química , Papaína/metabolismo , alfa-Amilasas , Hidrolisados de Proteína/química
9.
Biomater Sci ; 12(9): 2312-2320, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38497434

RESUMEN

Postsurgical treatment comprehensively benefits from the application of tissue-adhesive injectable hydrogels, which reduce postoperative complications by promoting wound closure and tissue regeneration. Although various hydrogels have been employed as clinical tissue adhesives, many exhibit deficiencies in adhesive strength under wet conditions or in immunomodulatory functions. Herein, we report the development of reactive oxygen species (ROS) scavenging and tissue-adhesive injectable hydrogels composed of polyamine-modified gelatin crosslinked with the 4-arm poly (ethylene glycol) crosslinker. Polyamine-modified gelatin was particularly potent in suppressing the secretion of proinflammatory cytokines from stimulated primary macrophages. This effect is attributed to its ability to scavenge ROS and inhibit the nuclear translocation of nuclear factor kappa-B. Polyamine-modified gelatin-based hydrogels exhibited ROS scavenging abilities and enhanced tissue adhesive strength on collagen casing. Notably, the hydrogel demonstrated exceptional tissue adhesive properties in a wet environment, as evidenced by its performance using porcine small intestine tissue. This approach holds significant promise for designing immunomodulatory hydrogels with superior tissue adhesion strength compared to conventional medical materials, thereby contributing to advancements in minimally invasive surgical techniques.


Asunto(s)
Gelatina , Hidrogeles , Especies Reactivas de Oxígeno , Adhesivos Tisulares , Hidrogeles/química , Hidrogeles/administración & dosificación , Hidrogeles/farmacología , Animales , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Ratones , Porcinos , Gelatina/química , Polietileneimina/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/administración & dosificación , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Polietilenglicoles/química , Inyecciones , Citocinas/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/efectos de los fármacos
10.
Food Chem ; 445: 138801, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387316

RESUMEN

Frog skin, a by-product of Quasipaa Spinosa farming, is rich in protein and potentially a valuable raw material for obtaining antioxidant peptides. This study used papain combined with acid protease to digest frog skin in a two-step enzymatic hydrolysis method. Based on a single factor and response surface experiments, experimental conditions were optimized, and the degree of hydrolysis was 30 %. A frog skin hydrolysate (QSPH-Ⅰ-3) was obtained following ultrafiltration and gel filtration chromatography. IC50 for DPPH, ABTS, and hydroxyl radical scavenging capacities were 1.68 ± 0.05, 1.20 ± 0.14 and 1.55 ± 0.11 mg/mL, respectively. Peptide sequences (17) were analyzed and, through molecular docking, peptides with low binding energies for KEAP1 were identified, which might affect the NRF2-KEAP1 pathway. These findings suggest protein hydrolysates and antioxidant peptide derivatives might be used in functional foods.


Asunto(s)
Antioxidantes , Depuradores de Radicales Libres , Antioxidantes/química , Hidrólisis , Proteína 1 Asociada A ECH Tipo Kelch , Depuradores de Radicales Libres/química , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2 , Péptidos/química , Hidrolisados de Proteína/química
11.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38338912

RESUMEN

Despite significant advancements in understanding the causes and progression of tumors, cancer remains one of the leading causes of death worldwide. In light of advances in cancer therapy, there has been a growing interest in drug repurposing, which involves exploring new uses for medications that are already approved for clinical use. One such medication is edaravone, which is currently used to manage patients with cerebral infarction and amyotrophic lateral sclerosis. Due to its antioxidant and anti-inflammatory properties, edaravone has also been investigated for its potential activities in treating cancer, notably as an anti-proliferative and cytoprotective drug against side effects induced by traditional cancer therapies. This comprehensive review aims to provide updates on the various applications of edaravone in cancer therapy. It explores its potential as a standalone antitumor drug, either used alone or in combination with other medications, as well as its role as an adjuvant to mitigate the side effects of conventional anticancer treatments.


Asunto(s)
Esclerosis Amiotrófica Lateral , Neoplasias , Fármacos Neuroprotectores , Humanos , Edaravona/uso terapéutico , Fármacos Neuroprotectores/farmacología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Antioxidantes/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/inducido químicamente , Depuradores de Radicales Libres/farmacología
12.
Drug Res (Stuttg) ; 74(2): 67-76, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38346682

RESUMEN

Parkinson's disease is the loss of dopaminergic neurons in the substantial nigra part of the brain leading to neurodegeneration. Whereas, reactive oxygen species and mitochondrial impairment are considered to be the major pathophysiology of neurodegeneration. The benzylidene-based 2-chloroquinolin derivatives were synthesized and characterized by FT-IR, NMR, and MS spectrometry which were screened using various in-silico approaches. The designed compounds were further assessed using in-vitro cytotoxicity assay by the MTT method, DPPH assay, and Glutathione measurements in the SHSY5Y neuroblastoma cell lines. The compounds JD-7 and JD-4 were found to have a binding affinity of - 7.941 and - 7.633 kcal/mol with an MMGBSA score of - 64.614 and - 62.817 kcal/mol. The compound JD-7 showed the highest % Cell viability of 87.64% at a minimal dose of 125 µg/mL by the MTT method. The neurotoxicity effects were observed at increasing concentrations from 0 to 125, 250, and 500 µg/mL. Further, free radical scavenging activity for the JD-7 was found to be 36.55 at lowest 125 µg/mL concentrations. At 125 µg/mL, GSH % and GSSG % were found to be increasing in rotenone treatment, whereas JD-7 and JD-4 were found in the downregulation of glutathione level in the pre-treated rotenone SHSY5Y neuroblastoma cell lines. The benzylidene-based chloroquinolin derivatives were synthesized, and among the compounds JD-1 to JD-13, the compounds JD-7, and JD-4 were found to have having highest % cell viability, free radical scavenging molecules, and glutathione levels in the SHSY5Y neuroblastoma cell lines and could be used as free radical scavengers in Parkinson's disease.


Asunto(s)
Neuroblastoma , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Rotenona , Espectroscopía Infrarroja por Transformada de Fourier , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo
13.
Adv Healthc Mater ; 13(12): e2303229, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38298062

RESUMEN

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.


Asunto(s)
Cerio , Cobre , Macrófagos , Factor 2 Relacionado con NF-E2 , Cicatrización de Heridas , Factor 2 Relacionado con NF-E2/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Ratones , Cerio/química , Cerio/farmacología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Cobre/química , Cobre/farmacología , Células RAW 264.7 , Diabetes Mellitus Experimental/metabolismo , Radical Hidroxilo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Masculino , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Antioxidantes/farmacología , Antioxidantes/química
14.
Chem Biodivers ; 21(5): e202302115, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38415904

RESUMEN

There is a burgeoning focus on utilizing the antifungal and antioxidant properties of essential oils derived from various plants as a modern and natural approach to combat the growth of fungi that contaminate food. In this study, we used essential oils extracted from Thymus daenensis Celak. subsp. daenensis to address three mycotoxin-producing species of Aspergillus, specifically A. flavus, A. parasiticus, and A. niger, all of which are recognized contaminants of food and agricultural products. Concurrently, the antioxidant properties of the essential oils were evaluated, revealing their noteworthy role in the antifungal activity. Essential oils were derived from T. daenensis subsp. daenensis was observed to have a significant inhibitory effect on all three species of Aspergillus, as evidenced by the minimum inhibitory concentration (MIC) ranging from 575 to 707 ppm and the half-maximal inhibitory concentration (IC50) ranging from 237 to 280 ppm. These results confirm the strong antifungal activity of the essential oils. Furthermore, the essential oil exhibited free radical scavenging activity, resulting in an EC50 value of 37.1 µg/ml. In summary, T. daenensis subsp. daenensis essential oil demonstrated a competitive advantage over other similar plants and synthetic antibiotics. This indicates the promising potential of this essential oil as a natural antifungal agent to control Aspergillus growth and mycotoxin contamination. It offers an alternative or complementary approach to conventional antifungal agents and could be a valuable addition to the arsenal of natural remedies to address fungal contamination in food and agricultural products.


Asunto(s)
Antifúngicos , Aspergillus , Depuradores de Radicales Libres , Pruebas de Sensibilidad Microbiana , Aceites Volátiles , Timol , Thymus (Planta) , Aceites Volátiles/farmacología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Aspergillus/efectos de los fármacos , Aspergillus/química , Thymus (Planta)/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Timol/farmacología , Timol/química , Monoterpenos/farmacología , Monoterpenos/química , Monoterpenos/aislamiento & purificación
15.
Int J Mol Sci ; 25(3)2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38338887

RESUMEN

Vascularized composite allotransplantation (VCA) represents a promising reconstructive solution primarily conducted to improve quality of life. However, tissue damage caused by cold-ischemia (CI) storage prior to transplant represents a major factor limiting widespread application. This study investigates the addition of the novel free radical scavenger PrC-210 to UW Organ Preservation Solution (UW Solution) to suppress CI-induced skeletal muscle injury in a rat hind limb amputation model. Lewis rats received systemic perfusion of UW solution +/- PrC-210 (0 mM control, 10 mM, 20 mM, 30 mM, or 40 mM), followed by bilateral transfemoral amputation. Limbs were stored in 40 mL of the same perfusate at 4 °C for 48 h. Muscle punch biopsies were taken at set times over the 48 h cold-storage period and analyzed for caspase-3,7 activity, cytochrome C levels, and qualitative histology. A single 15 s perfusion of PrC-210-containing UW Solution conferred a dose-dependent reduction in CI-induced muscle cell death over 48 h. In the presence of PrC-210, muscle cell mitochondrial cytochrome C release was equivalent to 0 h controls, with profound reductions in the caspase-3,7 apoptotic marker that correlated with limb histology. PrC-210 conferred complete prevention of ROS-induced mitochondrial lysis in vitro, as measured by cytochrome C release. We conclude that the addition of 30 mM PrC210 to UW Solution conferred the most consistent reduction in CI limb damage, and it warrants further investigation for clinical application in the VCA setting.


Asunto(s)
Aloinjertos Compuestos , Diaminas , Soluciones Preservantes de Órganos , Daño por Reperfusión , Compuestos de Sulfhidrilo , Ratas , Animales , Depuradores de Radicales Libres , Caspasa 3 , Aloinjertos Compuestos/patología , Citocromos c , Calidad de Vida , Ratas Endogámicas Lew , Glutatión/farmacología , Alopurinol/farmacología , Insulina/farmacología , Isquemia , Preservación de Órganos , Frío , Daño por Reperfusión/patología , Rafinosa , Adenosina
16.
J Phys Chem B ; 127(51): 11045-11053, 2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38103025

RESUMEN

Rubiadin (RBD), an anthraquinone derivative, is obtained from Rubia cordifolia, a plant species classified under the Rubiaceae family. Rubiadin has proven beneficial properties, such as anticancer, neuroprotective, anti-inflammatory, and antidiabetic activity. The antioxidant activity of this molecule was suggested by some experimental results but has not been clearly established thus far. In this study, we employ DFT calculations to comprehensively assess the mechanism and kinetics of the HO•/HOO• radical scavenging activity of this compound in relation to solvents. RBD showed moderate HO• radical scavenging activity, with rate constants of 2.95 × 108 and 1.82 × 1010 M-1 s-1 in lipid and polar media, respectively. In the aqueous solution, the compound exhibited remarkable superoxide anion radical scavenging activity (k = 4.93 × 108 M-1 s-1) but modest HOO• antiradical activity. RBD also showed promising antiradical activity against a variety of radicals (CCl3O•, CCl3OO•, NO2, SO4•-, and N3•), while experimental and computational results confirmed that RBD has moderate activity in DPPH/ABTS•+ assays. Thus, RBD is predicted to be a good, albeit selective, radical scavenger.


Asunto(s)
Antraquinonas , Antioxidantes , Antioxidantes/farmacología , Antraquinonas/farmacología , Extractos Vegetales , Solventes , Depuradores de Radicales Libres/farmacología
17.
Int J Med Mushrooms ; 25(11): 1-10, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37831508

RESUMEN

We selected polypore mushrooms growing in the Mediterranean area of France to screen their antioxidant activity: Ganoderma applanatum, G. lucidum, Inonotus cuticularis, I. hispidus, Trametes hirsuta, and T. versicolor. Our work also evaluated antioxidant capacity from wild and cultivated G. lucidum fruiting bodies to optimize this biological property on human health. Dried fungal materials were sequentially extracted using cyclohexane, dichloromethane, ethanol, and water. Folin-Ciocalteu assay, oxygen radical absorbance capacity using DPPH and ORAC tests of the polypore extracts were assessed and compared. Among the 28 mushroom extracts tested, four exhibited significant antioxidant activity as ethanol extracts of I. cuticularis, T. hirsuta and wild and cultivated G. lucidum. The ethanol extracts of I. cuticularis and T. hirsuta revealed the highest values for the ORAC test, while the highest values for the Folin-Ciocalteu and DPPH tests were found for the ethanol extracts of cultivated G. lucidum and I. cuticularis. Further studies are needed to identify potential bioactive compounds, especially from I. cuticularis and G. lucidum grown under selected conditions and explore their benefits in the pharmaceutical and food industries.


Asunto(s)
Agaricales , Antioxidantes , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Agaricales/química , Depuradores de Radicales Libres/química , Trametes , Fenoles/química , Etanol
18.
Adv Healthc Mater ; 12(29): e2300819, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37698231

RESUMEN

Radiation-induced heart disease is a serious side effect of radiation therapy that can lead to severe consequences. However, effective and safe methods for their prevention and treatment are presently lacking. This study reports the crucial function of fullerenols in protecting cardiomyocytes from radiation injury. First, fullerenols are synthesized using a simple base-catalyzed method. Next, the as-prepared fullerenols are applied as an effective free radical scavenger and broad-spectrum antioxidant to protect against X-ray-induced cardiomyocyte injury. Their ability to reduce apoptosis via the mitochondrial signaling pathway at the cellular level is then verified. Finally, it is observed in animal models that fullerenols accumulate in the heart and alleviate myocardial damage induced by X-rays. This study represents a timely and essential analysis of the prevention and treatment of radiological myocardial injury, providing new insights into the applications of fullerenols for therapeutic strategies.


Asunto(s)
Fulerenos , Traumatismos por Radiación , Animales , Fulerenos/farmacología , Fulerenos/uso terapéutico , Antioxidantes , Depuradores de Radicales Libres , Miocitos Cardíacos
19.
Molecules ; 28(13)2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37446822

RESUMEN

This work addresses two research topics: the first concerns the specific/sensitive trapping of hydroxyl radicals (•OH), and the second concerns the efficacy of encapsulating natural antioxidants, potentially lengthening their preservation activity. For context, nano-titania was solar-irradiated to produce •OH, which was spectrofluorimetrically assessed, based on the selective aromatic hydroxylation of the non-fluorescent sodium terephthalate to 2-hydroxyterephthalate fluorophore. Fluorescence intensity is proportional to generated •OH. Thus, a simple/rapid indirect method was utilized to assess •OH precisely. Accordingly, novel photoluminescent system is outlined in order to assess the scavenging potentiality of •OH in date seed oil (DSO) in both its pure and encapsulated formulations (ECP-DSO), i.e., when fresh and 5 months after extraction and encapsulation, respectively. With the addition of 80 µg/mL DSO or ECP-DSO, the efficacy of •OH scavenging amounted to 25.12 and 63.39%, which increased to 68.65 and 92.72% when 200 µg/mL DSO or ECP-DSO, respectively, was added. Moreover, the IC50 of DSO and ECP-DSO is 136.6 and 62.1 µg/mL, respectively. Furthermore, DSO and ECP-DSO decreased the kinetics for producing •OH by ≈20 and 40%, respectively, relative to •OH generated in the absence of antioxidant. This demonstrates the benefits of encapsulation on the preservation activity of natural antioxidants, even after five months after extraction, in terms of its interesting activity when compared to synthetic antioxidants. The developed fluorimetric •OH probing upgrades antioxidant medicines, thus paving the way for theoretical/practical insights on mechanistic hydroxyl radical-damaging biology.


Asunto(s)
Antioxidantes , Radical Hidroxilo , Antioxidantes/farmacología , Espectrometría de Fluorescencia , Semillas , Extractos Vegetales , Depuradores de Radicales Libres
20.
Molecules ; 28(11)2023 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-37298867

RESUMEN

Loach, rich in nutrients, such as proteins, amino acids, and mineral elements, is being gradually favored by consumers. Therefore, in this study, the antioxidant activity and structural characteristics of loach peptides were comprehensively analyzed. The loach protein (LAP) with a molecular weight between 150 and 3000 Da was graded by ultrafiltration and nanofiltration processes, which exhibited excellent scavenging activity against DPPH radical (IC50 2.91 ± 0.02 mg/mL), hydroxyl radical (IC50 9.95 ± 0.03 mg/mL), and superoxide anion radical (IC50 13.67 ± 0.33 mg/mL). Additionally, LAP was purified by gel filtration chromatography, and two principal components (named as LAP-I and LAP-II) were isolated. A total of 582 and 672 peptides were identified in LAP-I and LAP-II, respectively, through structural analysis. The XRD results revealed that LAP-I and LAP-II had an irregular amorphous structure. The 2D-NMR spectroscopy results suggested that LAP-I had a compact stretch conformation in the D2O solution, while LAP-II had a folded conformation. Overall, the study results suggested that loach peptide could be a potential antioxidant agent and might provide valuable information for chain conformation and antioxidant mechanism research further.


Asunto(s)
Antioxidantes , Hidrolisados de Proteína , Antioxidantes/química , Hidrolisados de Proteína/química , Depuradores de Radicales Libres/química , Péptidos/química , Proteínas , Superóxidos/química
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