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1.
Mediators Inflamm ; 2020: 9078956, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32351323

RESUMEN

Jungia sellowii Less. (Asteraceae) is a native plant found in Southeast Brazil used traditionally to treat inflammatory diseases. This study was conducted (1) to investigate the toxicity of the crude extract (CE) and (2) to investigate the mechanism of the anti-inflammatory action of J. sellowii L. roots. The potential acute toxicity of CE was performed by administration of only different doses of CE (500, 1,000, and 2,000 i.p.) on mice for 14 days. The anti-inflammatory effect was evaluated using carrageenan-induced acute pleural cavity inflammation in a mouse model, evaluated through the following inflammatory variables: leukocyte, protein concentrations of the exudate, myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), and proinflammatory cytokine (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin- (IL-) 6, and IL-12) levels in mouse pleural fluid leakage. The p65 protein phosphorylation of nuclear factor NF-kappa B (p65 NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were analyzed in lung tissue. Our results demonstrated that the administration of CE up to 2,000 mg/kg did not present a toxic effect. In addition, the pretreatment of mice with CE; its derived fractions (aqueous fraction (AqF), butanol fraction (BuOHF), and ethyl acetate fraction (EtOAcF)); and isolated compounds (curcuhydroquinone O-ß-glucose (CUR) and α and ß piptizol (Pip)) reduced the following inflammatory variables: neutrophils, protein concentrations of the exudate, MPO, ADA, NOx, and proinflammatory cytokine (TNF-α, IFN-γ, IL-6, and IL-12) levels in mouse pleural fluid leakage. The compounds CUR and Pip also decreased the p65 protein phosphorylation of NF-kappa B and p38 (MAPK) in lung tissue. J. sellowii L. has important anti-inflammatory activity with potential applications in drug development against inflammatory disorders. These effects found can be attributed to the ability of the new isolated compounds CUR and Pip to suppress p65 NF-κB and p-p38 MAPK pathways.


Asunto(s)
Antiinflamatorios/farmacología , Asteraceae , Mediadores de Inflamación/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Adenosina Desaminasa/metabolismo , Animales , Asteraceae/química , Células Cultivadas , Regulación hacia Abajo , Femenino , Mediadores de Inflamación/análisis , Ratones , Extractos Vegetales/toxicidad , Transducción de Señal/efectos de los fármacos
2.
Mediators Inflamm ; 2020: 4620251, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32410853

RESUMEN

OBJECTIVE: The aim of this study was to investigate the anti-inflammatory effects of the crude extract (CE), derived fraction, and isolated compounds from Calea pinnatifida leaves in a mouse model of pulmonary neutrophilia. METHODS: The CE and derived fractions, hexane, ethyl acetate, and methanol, were obtained from C. pinnatifida leaves. The compounds 3,5- and 4,5-di-O-E-caffeoylquinic acids were isolated from the EtOAc fraction using chromatography and were identified using infrared spectroscopic data and nuclear magnetic resonance (1H and 13C NMR). Leukocytes count, protein concentration of the exudate, myeloperoxidase (MPO) and adenosine deaminase (ADA), and nitrate/nitrite (NO x ), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), and interleukin-17A (IL-17A) levels were determined in the pleural fluid leakage after 4 h of pleurisy induction. We also analyzed the effects of isolated compounds on the phosphorylation of both p65 and p38 in the lung tissue. RESULTS: The CE, its fractions, and isolated compounds inhibited leukocyte activation, protein concentration of the exudate, and MPO, ADA, NO x , TNF-α, IL-1ß, and IL-17A levels. 3,5- and 4,5-di-O-E-caffeoylquinic acids also inhibited phosphorylation of both p65 and p38 (P < 0.05). CONCLUSION: This study demonstrated that C. pinnatifida presents important anti-inflammatory properties by inhibiting activated leukocytes and protein concentration of the exudate. These effects were related to the inhibition of proinflammatory mediators. The dicaffeoylquinic acids may be partially responsible for these anti-inflammatory properties through the inhibition of nuclear transcription factor kappa B and mitogen-activated protein kinase pathways.


Asunto(s)
Asteraceae/química , Inflamación/tratamiento farmacológico , Trastornos Leucocíticos/tratamiento farmacológico , Enfermedades Pulmonares/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Adenosina Desaminasa/metabolismo , Animales , Antiinflamatorios/farmacología , Carragenina , Modelos Animales de Enfermedad , Femenino , Inflamación/inducido químicamente , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Trastornos Leucocíticos/inducido químicamente , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Enfermedades Pulmonares/inducido químicamente , Ratones , Nitratos/química , Nitritos/química , Peroxidasa/metabolismo , Fosforilación , Pleuresia/tratamiento farmacológico , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
3.
Fundam Clin Pharmacol ; 38(1): 168-182, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37558213

RESUMEN

INTRODUCTION: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities. OBJECTIVE: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice. RESULTS: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture. CONCLUSION: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.


Asunto(s)
Dihidropiridinas , Interleucina-10 , Interleucina-6 , Ratones , Animales , Citocinas , Antiinflamatorios/farmacología , Factor de Necrosis Tumoral alfa , Lipopolisacáridos/farmacología , Óxido Nítrico
4.
Rev. bras. queimaduras ; 20(1): 70-74, 2021.
Artículo en Portugués | LILACS | ID: biblio-1380064

RESUMEN

OBJETIVO: Discorrer sobre a atuação multiprofissional no atendimento a um paciente grande queimado em uma Unidade de Terapia Intensiva (UTI) geral. RELATO DO CASO: Paciente do sexo feminino, 27 anos, com história de asma, obesidade. Vítima de queimadura por álcool, autoinfligida (tentativa de suicídio), apresentando queimaduras de 2° e 3° graus em 65% da superfície corporal, tendo sido atingidas as regiões: cervical, torácica e abdominal, em membros superiores e inferiores, face e vias aéreas. CONSIDERAÇÕES FINAIS: Foram muitos os desafios enfrentados durante essa internação, destacando-se as dificuldades de manejar um paciente grande queimado em uma UTI geral. Espera-se que esse caso represente um estímulo para a realização de novas pesquisas no sentido de repensar, modificar, aprimorar e instrumentalizar a equipe multiprofissional em relação ao cuidado ao paciente queimado.


OBJECTIVE: To discuss the multidisciplinary work in the care of a large burned patient in a general Intensive Care Unit (ICU). CASE REPORT: Female patient, 27 years old, with history of asthma, obesity. Self-inflicted alcohol burn victim (attempted suicide), with burns of 2nd and 3rd degrees on 65% of the body surface, having been affected: cervical, thoracic and abdominal regions, upper and lower limbs, face and pathways aerial. FINAL CONSIDERATIONS: There were many challenges faced during this hospitalization, highlighting the difficulties of managing a large burned patient in a general ICU. This case is expected to represent a stimulus for further research in the sense of rethinking, modifying, improving and equipping the multiprofessional team in relation to the care for burned patients.


Asunto(s)
Humanos , Femenino , Adulto , Grupo de Atención al Paciente , Intento de Suicidio , Quemaduras , Unidades de Cuidados Intensivos
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