RESUMO
Micrometam C is a core of novel marine compound isolated from the mangrove associates Micromelum falcatum. In this study, we investigated the protective effects of micrometam C in inflammation models in the transgenic zebrafish line Tg (corola: eGFP) and RAW264.7 macrophages. We found that micrometam C significantly suppressed the migration of immune cells in tail-cutting-induced inflammation in transgenic zebrafish and reduced lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) in both zebrafish and macrophages. In addition, micrometam C also restored LPS-induced reduction of endogenous antioxidants, such as catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). The protective effects of micrometam C were in parallel to its inhibition of NADPH oxidase and nuclear factor-kappa-binding (NF-κB) activity. Thus, the present results demonstrate that micrometam C protects against LPS-induced inflammation possibly through its antioxidant property.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Inflamação/tratamento farmacológico , Animais , Antioxidantes , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Macrófagos , Camundongos , Estrutura Molecular , NADPH Oxidases/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Explosão Respiratória , Cauda , Peixe-ZebraRESUMO
Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.
Assuntos
Inibidores da Angiogênese/farmacologia , Catecóis/farmacologia , Lignanas/farmacologia , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Proteína Oncogênica v-akt/efeitos dos fármacos , Nadadeiras de Animais/efeitos dos fármacos , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Catecóis/química , Movimento Celular/efeitos dos fármacos , Embrião não Mamífero , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lignanas/química , Fosforilação/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/farmacologia , Peixe-ZebraRESUMO
Two new quinoldione alkaloids, methyl 2-(3-hydroxy-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetate (1) and 3-hydroxy-1-methyl-3-(2-oxopropyl)quinoline-2,4(1H,3H)-dione (2), and two quinolinone alkaloids previously synthesized but first isolated as natural products, N-methylflindersine (3) and 4-hydroxy-3-methoxy-1-methyl-2(1H)-quinolinone (4), were isolated from the stem bark of Micromelum falcatum, together with the known N-methylswietenidine-B (5). Their structures were established mainly on the basis of 1D- and 2D-NMR techniques. All compounds were evaluated for toxicity towards brine shrimp larvae, and 3 showed strong toxicity with an LD(50) value of 1.39 microg/ml.