title: A natural antiviral and immunomodulatory compound with antiangiogenic properties.
abstract: 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.
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, Piso 4°, Ciudad Universitaria, C-1428GBA, Buenos Aires, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bueno
authors.forename: María G
authors.initials: MG
authors.lastname: Lombardi
authors.forename: María E
authors.initials: ME
authors.lastname: Sales
authors.forename: Laura E
authors.initials: LE
authors.lastname: Alché
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002633:Chemotaxis; D015195:Drug Design; D005260:Female; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism; D031585:Melia / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010940:Plant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D020533:Angiogenesis Inhibitors; D000998:Antiviral Agents; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D010455:Peptides; D010936:Plant Extracts; D010940:Plant Proteins; D042461:Vascular Endothelial Growth Factor A; C058031:meliacin