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1.
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 Amiotrófica Lateral , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Feminino , Gravidez , Esclerose Amiotrófica Lateral/tratamento farmacológico , Antioxidantes/uso terapêutico , Antipirina , Edaravone/farmacologia , Edaravone/uso terapêutico , Sequestradores de Radicais Livres/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Placenta
2.
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
3.
Int J Biol Macromol ; 262(Pt 2): 130260, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368984

RESUMO

Radical scavengers were employed to evaluate the influence of various active species (•OH, •O, and H2O2) on the rheological properties, antioxidant activity, and molecular conformation of chitosan under solution plasma process (SPP) degradation. ESR analysis showed that •OH and •O radicals played important roles in SPP degradation. The results of rheological properties and antioxidant activity indicated that the •OH scavenger (tert-butanol), •O scavenger (1, 4-benzoquinone), and H2O2 scavenger (MnO2) remarkably inhibited the decrease of G' and G" of the degraded chitosan, the formation of gel structure, and the increase of antioxidant activity. The analysis of molecular conformation of the chitosan by particle size analysis, atomic force microscopy (AFM), and high performance size exclusion chromatography coupled with multi-angle laser light scattering (HPSEC-MALLS) revealed that the decrease of particle size, molecular aggregation, and molecular weight of chitosan was inhibited after the addition of radical scavengers. An evident effect of radical scavengers on the hard sphere conformation of chitosan was observed. It was found that the above effects were strongly dependent on the scavenger concentration. These results proved that •OH, •O, and H2O2 played important roles in SPP treatment. For the rheological properties and molecular conformation, H2O2 exhibited the greatest impact. For the antioxidant activity and molecular weight, •OH presented the biggest influence. Besides, •O expressed the weakest effect. This study will be beneficial to reveal the action mechanisms of SPP technology to the degradation of chitosan.


Assuntos
Antioxidantes , Quitosana , Antioxidantes/farmacologia , Antioxidantes/química , Quitosana/química , Peróxido de Hidrogênio/química , Compostos de Manganês , Óxidos , Radicais Livres , Conformação Molecular , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
4.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338912

RESUMO

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.


Assuntos
Esclerose Amiotrófica Lateral , Neoplasias , Fármacos Neuroprotetores , Humanos , Edaravone/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Esclerose Amiotrófica Lateral/tratamento farmacológico , Antioxidantes/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Sequestradores de Radicais Livres/farmacologia
5.
Drug Res (Stuttg) ; 74(2): 67-76, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38346682

RESUMO

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.


Assuntos
Neuroblastoma , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Rotenona , Espectroscopia de Infravermelho com Transformada de Fourier , Espécies Reativas de Oxigênio/metabolismo , Glutationa/metabolismo
6.
Neuroscience ; 540: 1-11, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38242279

RESUMO

Mitochondrial dysfunction, which results in the overproduction of oxygen free radicals, is a crucial mechanism underlying cerebral ischemia-reperfusion injury. 4'-Hydroxyl-2-substituted phenylnitronyl nitroxide (HPN), which is an antioxidant and free radical scavenger, can effectively scavenge oxygen free radicals, suggesting its potential as a protective agent against cerebral ischemia-reperfusion injury. In this study, we investigated the effects of HPN on mitochondrial function and apoptosis following cerebral ischemia/reperfusion injury in rats. Healthy adult SD rats were chosen as the experimental subjects, and the rat ischemia/reperfusion injury model was generated using the modified Zea Longa method. The administration of HPN significantly enhanced the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Additionally, HPN effectively preserved the morphology and function of mitochondria, reduced the protein and gene expression of Caspase-3 and Bax, increased the protein and gene expression of Bcl-2, mitigated neuronal apoptosis, improved neurological deficits, and decreased the volume of cerebral infarction. Of interest, the protective effect on brain tissue was more evident with increasing doses of HPN. These findings indicate that HPN can serve as an effective protective agent against cerebral ischemia-reperfusion injury.


Assuntos
Isquemia Encefálica , Doenças Mitocondriais , Óxidos de Nitrogênio , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Sequestradores de Radicais Livres/farmacologia , Ratos Sprague-Dawley , Estresse Oxidativo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral , Antioxidantes/farmacologia , Apoptose , Superóxido Dismutase/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Substâncias Protetoras/farmacologia , Reperfusão , Radicais Livres
7.
Life Sci ; 336: 122319, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38035993

RESUMO

Various strategies can be employed to prevent and manage altitude illnesses, including habituation, oxygenation, nutritional support, and medication. Nevertheless, the utilization of drugs for the prevention and treatment of hypoxia is accompanied by certain adverse effects. Consequently, the quest for medications that exhibit minimal side effects while demonstrating high efficacy remains a prominent area of research. In this context, it is noteworthy that free radical scavengers exhibit remarkable anti-hypoxia activity. These scavengers effectively eliminate excessive free radicals and mitigate the production of reactive oxygen species (ROS), thereby safeguarding the body against oxidative damage induced by plateau hypoxia. In this review, we aim to elucidate the pathogenesis of plateau diseases that are triggered by hypoxia-induced oxidative stress at high altitudes. Additionally, we present a range of free radical scavengers as potential therapeutic and preventive approaches to mitigate the occurrence of common diseases associated with hypoxia at high altitudes.


Assuntos
Doença da Altitude , Sequestradores de Radicais Livres , Humanos , Sequestradores de Radicais Livres/farmacologia , Doença da Altitude/tratamento farmacológico , Altitude , Estresse Oxidativo , Hipóxia/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico
8.
Drug Chem Toxicol ; 47(2): 227-234, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37553904

RESUMO

In recent years, the cardiotoxicity and hepatotoxicity induced by chemotherapeutic drugs such as cisplatin (CP) have become significant issues. The current research looks into the effects of sodium hydrosulfide (NaHS) on CP-induced hepatotoxicity and cardiotoxicity in rats. A total of 32 male Sprague Dawley rats were separated into four different groups: (1) control group, received only normal saline; (2) NaHS group, was intraperitoneally injected with NaHS (200 µg/kg/d, dissolved in saline) for 15 days; (3) CP group, was intraperitoneally injected only one dose of CP (5 mg/kg) and (4) CP plus NaHS group, received CP along with NaHS. Blood and tissues samples were harvested for biochemical, histopathological, and immunohistochemical investigations. To determine the data's statistical significance, a one-way analysis of variance was used. CP injection significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), Creatine phospho kinase (CK-MB), cholesterol, low-density lipoprotein (LDL), triglyceride (TG), and lipid peroxidation levels, while high-density lipoprotein (HDL), albumin, glutathione peroxidase, superoxide dismutase, and catalase (CAT) levels were significantly reduced with pathological alterations in liver and heart tissues. Co-treatment NaHS with CP ameliorates the biochemical and histological parameters. Also, Treatment solely with CP resulted in increased tissue expression of interleukin-1ß (IL-1ß) in liver and heart but co-treatment NaHS with CP reduced the expression of this inflammatory factor. We conclude that NaHS operates in the liver and heart as an anti-inflammatory and powerful free radicals' scavenger to inhibit the toxic effects of CP, both at the biochemical and histopathological levels.


NaHS protects the liver and heart against Cisplatin-induced toxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Cisplatino , Sulfetos , Ratos , Masculino , Animais , Cisplatino/toxicidade , Cardiotoxicidade , Ratos Sprague-Dawley , Fígado , Sequestradores de Radicais Livres/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Estresse Oxidativo , Antioxidantes/farmacologia
9.
J Phys Chem B ; 127(51): 11045-11053, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38103025

RESUMO

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.


Assuntos
Antraquinonas , Antioxidantes , Antioxidantes/farmacologia , Antraquinonas/farmacologia , Extratos Vegetais , Solventes , Sequestradores de Radicais Livres/farmacologia
10.
J Org Chem ; 88(24): 17237-17248, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38011833

RESUMO

Rosmarinic acid (RA) is reported in separate studies to be either an inducer or reliever of oxidative stress, and this contradiction has not been resolved. In this study, we present a comprehensive examination of the radical scavenging activity of RA using density functional theory calculations in comparison with experimental data. In model physiological media, RA exhibited strong HO• radical scavenging activity with overall rate constant values of 2.89 × 1010 and 3.86 × 109 M-1 s-1. RA is anticipated to exhibit excellent scavenging properties for HOO• in an aqueous environment (koverall = 3.18 × 108 M-1 s-1, ≈2446 times of Trolox) following the hydrogen transfer and single electron transfer pathways of the dianion state. The neutral form of the activity is equally noteworthy in a lipid environment (koverall = 3.16 × 104 M-1 s-1) by the formal hydrogen transfer mechanism of the O6(7,15,16)-H bonds. Chelation with RA may prevent Cu(II) from reduction by the ascorbic acid anion (AA-), hence blocking the OIL-1 pathway, suggesting that RA in an aqueous environment also serves as an OIL-1 antioxidant. The computational findings exhibit strong concurrence with the experimental observations, indicating that RA possesses a significant efficacy as a radical scavenger in physiological environments.


Assuntos
Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Estresse Oxidativo , Ácido Ascórbico , Água/química , Hidrogênio , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
11.
J Antibiot (Tokyo) ; 76(12): 731-734, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37845350

RESUMO

A new formanilide dimer, fraxinin (1), and three known formanilides (2‒4) were isolated from the culture broth of Perenniporia fraxinea using silica gel and Sephadex LH-20 column chromatographies, medium-pressure liquid chromatography (MPLC), and preparative HPLC. The structures of these compounds were determined by spectroscopic methods, such as NMR and mass analysis, and by comparison of the spectra with previously reported data. The free radical scavenging activities of the isolated compounds were assessed using 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Compounds 1‒3 exhibited ABTS radical scavenging activity with IC50 values in the range of 57.2-250.2 µM. Compounds 2 and 4 marginally reduced disease incidence of powdery mildew with a control value of 42% at 1.0 mg ml-1 in cucumber leaf disk assay.


Assuntos
Antioxidantes , Sequestradores de Radicais Livres , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Antioxidantes/farmacologia , Antioxidantes/química , Compostos de Bifenilo/química , Picratos/química
12.
Int J Nanomedicine ; 18: 4601-4616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600119

RESUMO

Background: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy. Methods: CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model. Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury. Conclusion: The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.


Assuntos
Colite , Sequestradores de Radicais Livres , Indóis , Nanotubos , Polímeros , Espécies Reativas de Oxigênio , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Polímeros/química , Polímeros/farmacologia , Polímeros/uso terapêutico , Colite/tratamento farmacológico , Colite/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Polaridade Celular , Cério , Animais , Camundongos , Células RAW 264.7 , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
13.
Expert Rev Neurother ; 23(10): 859-866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37646130

RESUMO

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. While pharmacotherapy options remain limited, the Food and Drug Administration (FDA) approved intravenous (IV) and oral edaravone for the treatment of ALS in 2017 and 2022, respectively. With the addition of oral edaravone, patients with ALS may exclusively use oral medications. AREAS COVERED: The authors performed a review of the published literature using the United States (US) National Library of Medicine's PubMed.gov resource to describe the pharmacokinetics, pharmacodynamics, safety, and efficacy of oral edaravone, as well as pertinent completed and ongoing clinical trials, including the oral edaravone clinical trial development program. The clinical profile of oral edaravone is also discussed. EXPERT OPINION: Edaravone has been shown to slow the rate of motor function deterioration experienced by patients with ALS. As the oral formulation has been approved, patients with ALS may use it alone or in combination with other approved therapeutics. Additional clinical trials and real-world evidence are ongoing to gain further understanding of the clinical profile of oral edaravone.


Assuntos
Esclerose Amiotrófica Lateral , Doenças Neurodegenerativas , Humanos , Edaravone/farmacocinética , Esclerose Amiotrófica Lateral/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Sequestradores de Radicais Livres/farmacologia , Administração Intravenosa
14.
Dalton Trans ; 52(28): 9673-9683, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37382407

RESUMO

In this paper, we used extracellular reactive oxygen radical scavenging assay and cellular antioxidant assay to investigate the antioxidant ability of Keggin-type polyoxometalates on the inside and outside of cells influenced by three different factors: heteroatom substitution, transition metal substitution and the number of vanadium substitutions. The results showed that the IC50 values of heteroatomic (P, Si, Ga) polyoxometalates on superoxide anion radical scavenging were 1.32 ± 0.00047 mg mL-1, 17.49 ± 2.47500 mg mL-1, and 66.99 ± 20.0227 mg mL-1, respectively. In comparison, PMo12 had the best ability to scavenge free radicals, and the SOD activity of PMo12 at 12.5 µmol L-1 increased by 50% compared with that of the unspiked drug, which played an antioxidant role; the scavenging effect of superoxide anion radicals of PMo11Mn in transition metals (Fe, Mn, Cu) instead of polyoxometalate (IC50 value 1.18 ± 0.0008 mg mL-1) was lower than that of unsubstituted PMo12 (IC50 value 1.32 ± 0.00047 mg mL-1), where PMo11Mn was nearly 1.5 times higher than PMo11Cu administration to reduce the number of cells by half; the PMo11V, PMo10V2, PMo9V3, PMo8V4, PMo7V5 hydroxyl radical scavenging rates (IC50 values) were 0.19 ± 0.0011 mg mL-1, 0.22 ± 0.0027 mg mL-1, 0.03 ± 0.0014 mg mL-1, 0.04 ± 0.0008 mg mL-1, and 0.11 ± 0.0005 mg mL-1, respectively, and in comparison, scavenging of PMo9V3 radicals was more effective and they acted as an antioxidant. Therefore, they can be used as good antioxidants in biological and pharmaceutical applications and play an important role in the treatment of tumours, cancer, Alzheimer's disease and other diseases.


Assuntos
Antioxidantes , Sequestradores de Radicais Livres , Antioxidantes/farmacologia , Sequestradores de Radicais Livres/farmacologia , Superóxidos , Espécies Reativas de Oxigênio
15.
J Phys Chem B ; 127(20): 4364-4373, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37163390

RESUMO

Benzimidazole-arylhydrazone hybrids showed promising potential as multifunctional drugs for the treatment of neurodegenerative disorders. The neuroprotection studies conducted using an in vitro model of H2O2-induced oxidative stress on the SH-SY5Y cell line revealed a remarkable activity of the compound possessing a vanilloid structural fragment. The cell viability was preserved up to 84% and this effect was significantly higher than the one exerted by the reference compounds melatonin and rasagiline. Another compound with a catecholic moiety demonstrated the second-best neuroprotective activity. Computational studies were further conducted to characterize in depth the antioxidant properties of both compounds. The possible radical scavenging mechanisms were estimated as well as the most reactive sites through which the compounds may deactivate a variety of free radicals. Both of the compounds are able to deactivate not only the highly reactive hydroxyl radicals but also alkoxyl and hydroperoxyl radicals, following hydrogen atom transfer or radical adduct formation mechanism. In nonpolar medium, 3e is predicted to react slightly faster than 3a with alkoxyl radicals and around two orders of magnitude faster than 3a with hydroperoxyl radicals. The most reactive sites for formal hydrogen atom transfer in 3a are the meta-hydroxy group in the phenyl ring in water and the amide N-H group in benzene; in 3e, the amide N-H group is more reactive in both solvents. The radical adduct formation can occur at several positions in 3a and 3e, the most active being C4, C6, and C14. The stability of the formed radicals was estimated by NBO calculations. The NBO calculations indicated that the spin density in the radicals formed by the abstraction of a hydrogen atom from the amide groups of both compounds is delocalized over the phenyl ring and the hydrazone chain. The obtained theoretical data for the better radical scavenging ability of the vanilloid hybrid corroborate its experimentally established better neuroprotective activity.


Assuntos
Peróxido de Hidrogênio , Neuroblastoma , Humanos , Neuroproteção , Radicais Livres/química , Hidrogênio , Amidas , Benzimidazóis/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Radical Hidroxila/química
16.
Molecules ; 28(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677790

RESUMO

Honokiol is a natural bisphenol neolignan present in the bark of Magnolia officinalis, whose extracts have been employed in oriental medicine to treat several disorders, showing a variety of biological properties, including antitumor activity, potentially related to radical scavenging. Six bisphenol neolignans with structural motifs related to the natural bioactive honokiol were synthesized. Their chain-breaking antioxidant activity was evaluated in the presence of peroxyl (ROO•) and hydroperoxyl (HOO•) radicals by both experimental and computational methods. Depending on the number and position of the hydroxyl and alkyl groups present on the molecules, these derivatives are more or less effective than the reference natural compound. The rate constant of the reaction with ROO• radicals for compound 7 is two orders of magnitude greater than that of honokiol. Moreover, for compounds displaying quinonic oxidized forms, we demonstrate that the addition of 1,4 cyclohexadiene, able to generate HOO• radicals, restores their antioxidant activity, because of the reducing capability of the HOO• radicals. The antioxidant activity of the oxidized compounds in combination with 1,4-cyclohexadiene is, in some cases, greater than that found for the starting compounds towards the peroxyl radicals. This synergy can be applied to maximize the performances of these new bisphenol neolignans.


Assuntos
Antioxidantes , Lignanas , Antioxidantes/farmacologia , Antioxidantes/química , Lignanas/farmacologia , Lignanas/química , Fenóis/farmacologia , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/farmacologia , Radicais Livres
17.
Naunyn Schmiedebergs Arch Pharmacol ; 396(5): 1043-1052, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36625947

RESUMO

The goal of the current study was to investigate the antioxidant, anti-ulcer, and analgesic properties of a metal-curcumin complex (MCC) utilizing different mouse and rat models. The antioxidant component of the analysis was completed in vitro, whereas the other activities were completed in vivo. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation scavenging test, the ferric-reducing antioxidant power (FRAP) assay, and the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging assay were used to measure the antioxidant activity. MCC demonstrated potent radical scavenging abilities. In all three experiments, Trolox served as the reference substance. When curcumin's radical scavenging abilities were compared, it became clear that MCC was a superior radical scavenger. Using the ethanol-induced technique on Sprague-Dawley rats, the anti-ulcerogenic effect was assessed. It shows that at an oral dosage of 100 mg/kg body weight, MCC might provide gastroprotection (b.w.). Additionally, we have examined MCC's potential as an analgesic. Swiss albino mice were used to measure the analgesic activity of MCC using the hot plate technique. At an oral dosage of 50 mg/kg b.w., MCC displayed analgesic efficacy. As a result, MCC could be useful in the management of inflammatory diseases.


Assuntos
Complexos de Coordenação , Curcumina , Ratos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Curcumina/farmacologia , Sequestradores de Radicais Livres/farmacologia , Ratos Sprague-Dawley , Analgésicos/farmacologia , Analgésicos/uso terapêutico
18.
Phytochemistry ; 207: 113580, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36587886

RESUMO

The free radical scavenging potency and mechanisms of seven representative natural coumestans were systematically evaluated using density functional theory (DFT) approach. Thermodynamic feasibility of different mechanisms was assessed by various physio-chemical descriptors involved in the double (2H+/2e‒) radical-trapping processes. Energy diagram and related transition state structures of the reaction between wedelolactone (WEL) and hydroperoxyl radical were constructed to further uncover the radical-trapping details. Results showed that the studied coumestans prefer to scavenge radicals via formal hydrogen atom transfer (fHAT) mechanism in the gas phase and non-polar environment, whereas sequential proton loss electron transfer (SPLET) is favored in polar media. Moreover, the feasibility of second fHAT and SPLET processes was also revealed. Sequential double proton loss double electron transfer (SdPLdET) mechanism represents the preferred pathway in aqueous solution at physiological pH. Our findings highlight the essential role of ortho-dihydroxyl group, noncovalent interaction and solvents on radical-trapping potency. 4'-OH in D-ring was found to be the most favorable site to trap radical for most of the studied coumestans, whereas 3-OH in A-ring for lucernol (LUN).


Assuntos
Antioxidantes , Prótons , Solventes/química , Antioxidantes/química , Hidrogênio/química , Modelos Teóricos , Radicais Livres/química , Termodinâmica , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121876, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36122463

RESUMO

A fluorescent gold nanocluster was used for determining peroxyl radical scavenging activity of antioxidants. Histidine was used as a green reducing and protective agent, and glutathione (GSH) enhanced the fluorescence intensity of histidine-stabilized gold nanoclusters (AuNCs) by ligand exchange process. When AAPH-induced oxidation of GSH occurred, the initial fluorescence intensity of GSH-capped AuNCs (λex = 450 nm λem = 502 nm) was decreased with static quenching. The decline of fluorescence intensity of the GSH-capped AuNCs upon peroxyl radical attack is diminished with the addition of antioxidants to the reaction medium, the difference in fluorescence intensity being related to peroxyl radical scavenging activity of antioxidants. The 50 % inhibitive concentration of related antioxidant compounds were determined and compared to those of crocin bleaching assay. Inhibition % of sage (Salvia officinalis L.) and green tea (Camellia sinensis) infusions against peroxyl radicals were investigated. The proposed assay can be used for simple and selective estimation of the peroxyl radical scavenging activity in complex matrices, as histidine-stabilized GSH-capped AuNCs were selective toward peroxyl radicals, not affected by other ROS at the studied concentrations.


Assuntos
Antioxidantes , Ouro , Antioxidantes/farmacologia , Histidina , Glutationa , Corantes , Sequestradores de Radicais Livres/farmacologia
20.
J Biomed Mater Res B Appl Biomater ; 111(4): 933-945, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36418224

RESUMO

Human hair proteins are recognized for their intrinsically high cysteine content. They can be solubilized while preserving their highly reductive thiol groups for free radical scavenging applications. The presence of aromatic and nucleophilic amino acids such as methionine, serine, phenylalanine, and threonine further contribute to the antioxidative potential of this material. Herein, utilizing the DPPH (2,2-diphenyl-1-picrylhydrazyl) and acellular 2',7'-dichlorodihydrofluorescein diacetate (H2 DCFDA) assays, keratins are demonstrated to possess the highest radical scavenging activity among the studied hair proteins. Consequently, protection against hydrogen peroxide-induced oxidative stress in human dermal fibroblasts (HDFs) cultured in human hair keratin supplemented media is demonstrated. Quenching of reactive oxygen species in the HDF is observed using the CellROX Green dye and the expression levels of antioxidant (HMOX1, SOD2, GPX1) and tumor suppressor (TP53) genes is analyzed using qPCR. Collectively, this study presents further evidence and demonstrates the in vitro application potential of hair proteins, especially keratins, as an antioxidizing supplement.


Assuntos
Antioxidantes , Sequestradores de Radicais Livres , Humanos , Espécies Reativas de Oxigênio/metabolismo , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Antioxidantes/farmacologia , Antioxidantes/química , Queratinas , Cabelo
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