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Microvasc Res ; 84(3): 235-41, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23006904

RESUMO

Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., reduces viral load and abolishes the inflammatory reaction and neovascularization during the development of herpetic stromal keratitis in mice. 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA, displays anti-herpetic and immunomodulatory activities in vitro. We investigated whether CDM interferes with the angiogenic process. CDM impeded VEGF transcription in LPS-stimulated and HSV-1-infected cells. It proved to have neither cytotoxic nor antiproliferative effect in HUVEC and to restrain HUVEC migration and formation of capillary-like tubes. Moreover, MA inhibits LMM3 tumor-induced neovascularization in vivo. We postulate that the antiangiogenic activity of CDM displayed in vitro as a consequence of their immunomodulatory properties is responsible for the antiangiogenic activity of MA in vivo, which would be associated with the lack of neovascularization in murine HSV-1-induced ocular disease.


Assuntos
Inibidores da Angiogênese/farmacologia , Antivirais/farmacologia , Fatores Imunológicos/farmacologia , Animais , Proliferação de Células , Química Farmacêutica/métodos , Quimiotaxia , Desenho de Fármacos , Feminino , Regulação da Expressão Gênica , Herpesvirus Humano 1/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Melia/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica , Peptídeos/farmacologia , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Fator A de Crescimento do Endotélio Vascular/biossíntese
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