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1.
Eur J Pharmacol ; 897: 173929, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33561444

RESUMO

Acute lung injury (ALI) remains to cause a high rate of mortality in critically ill patients. It is known that inflammation is a key factor in the pathogenesis of lipopolysaccharide (LPS)-induced ALI, which makes it a relevant approach to the treatment of ALI. In this study, we evaluated the potential of nasally instilled p-coumaric acid to prevent LPS-induced ALI in mice, by evaluating its effects on cellular and molecular targets involved in inflammatory response via in vitro and in silico approaches. Our results demonstrated that p-coumaric acid reduced both neutrophil accumulation and pro-inflammatory cytokine abundance, and simultaneously increased IL-10 production at the site of inflammation, potentially contributing to protection against LPS-induced ALI in mice. In the in vitro experiments, we observed inhibitory effects of p-coumaric acid against IL-6 and IL-8 production in stimulated A549 cells, as well as reactive oxygen species generation by neutrophils. In addition, p-coumaric acid treatment decreased neutrophil adhesion on the TNF-α-stimulated endothelial cells. According to the in silico predictions, p-coumaric acid reached stable interactions with both the ATP-binding site of IKKß as well as the regions within LFA-1, critical for interaction with ICAM-1, thereby suppressing the production of proinflammatory mediators and hindering the neutrophil infiltration, respectively. Collectively, these findings indicate that p-coumaric acid is a promising anti-inflammatory agent that can be used for developing a pharmaceutical drug for the treatment of ALI and other inflammatory disorders.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/administração & dosagem , Ácidos Cumáricos/administração & dosagem , Pulmão/efeitos dos fármacos , Células A549 , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Administração Intranasal , Animais , Anti-Inflamatórios/metabolismo , Sítios de Ligação , Técnicas de Cocultura , Simulação por Computador , Ácidos Cumáricos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo
2.
Environ Pollut ; 255(Pt 1): 113153, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520906

RESUMO

Plant essential oils are regarded as interesting alternative tools to be integrated into the management of pest insects. However, as they generally consist of mixtures of numerous molecules, the physiological basis for their action is unresolved. Here, we evaluated the effects of essential oil of the Neotropical plant Siparuna guianensis Aubl., commonly known as Negramina, against an important pest insect: the green peach aphid Myzus persicae (Sulzer), and also in two non-target natural enemies: the ladybeetle predators Coleomegilla maculata (DeGeer) and Eriopis connexa (Germar). In addition, we conducted a computational docking analysis for predicting the physical interactions between the two Negramina essential oil major constituents: ß-myrcene and 2-undocanone, and the transient receptor potential (TRP) channels as potential binding receptors in the aphid and ladybeetles. As the most important results, Negramina essential oil caused mortality in M. persicae aphids with an LC95 = 1.08 mg/cm2, and also significantly repelled the aphids at concentrations as low as 0.14 mg/cm2. Our computational docking analysis reinforced such selectivity actions as the Negramina essential oil major compounds (i.e., ß-myrcene and 2-undocanone) bound to the TRP channels of M. persicae but not to ladybeetle-related TRP channels. Interestingly, the exposure to the Negramina essential oil did not affect the predatory abilities of C. maculata but increased the abilities of E. connexa to prey upon M. persicae. Collectively, our findings provided a physiological basis for the insecticidal and selectivity potential of Negramina essential oil, reinforcing its potential as a tool to be used in integrated pest control programs.


Assuntos
Afídeos/efeitos dos fármacos , Besouros/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Laurales/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Monoterpenos Acíclicos/análise , Animais , Óleos Voláteis/química , Óleos de Plantas/química
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