La versión final de este artículo es de uso interno de la institución.
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


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. © 2012 Elsevier Inc.


Documento: Artículo
Título:A natural antiviral and immunomodulatory compound with antiangiogenic properties
Autor:Bueno, C.A.; Lombardi, M.G.; Sales, M.E.; Alché, L.E.
Filiación: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
CEFYBO-CONICET, Segunda Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 Piso 16, CP 1121ABG, Buenos Aires, Argentina
Palabras clave:1 cinnamoyl 3,11 dihydroxymeliacarpin; angiogenesis inhibitor; antivirus agent; immunomodulating agent; interleukin 6; lipopolysaccharide; meliacine; tumor necrosis factor alpha; unclassified drug; vasculotropin; vasculotropin A; animal cell; animal experiment; animal model; antiangiogenic activity; antiproliferative activity; article; cell function; cell stimulation; cell viability; chemotaxis; concentration response; controlled study; cytokine production; female; Herpes simplex virus 1; human; human cell; immunomodulation; in vitro study; in vivo study; migration inhibition; mouse; nonhuman; priority journal; protein expression; umbilical vein endothelial cell; Angiogenesis Inhibitors; Animals; Antiviral Agents; Cell Proliferation; Chemistry, Pharmaceutical; Chemotaxis; Drug Design; Female; Gene Expression Regulation; Herpesvirus 1, Human; Humans; Immunologic Factors; Lipopolysaccharides; Melia; Mice; Mice, Inbred BALB C; Neoplasms; Neovascularization, Pathologic; Peptides; Plant Extracts; Plant Proteins; Vascular Endothelial Growth Factor A; Human herpesvirus 1; Melia azedarach; Murinae; Mus
Página de inicio:235
Página de fin:241
Título revista:Microvascular Research
Título revista abreviado:Microvasc. Res.
CAS:vasculotropin, 127464-60-2; vasculotropin A, 489395-96-2; Angiogenesis Inhibitors; Antiviral Agents; Immunologic Factors; Lipopolysaccharides; Peptides; Plant Extracts; Plant Proteins; Vascular Endothelial Growth Factor A; meliacin


  • Albini, A., Tosetti, F., Benelli, R., Noonan, D.M., Tumor inflammatory angiogenesis and its chemoprevention (2005) Cancer Res., 65, pp. 10637-10641
  • Alché, L.E., Assad Ferek, G., Meo, M., Coto, C., Maier, M., An antiviral meliacarpin from leaves of Melia azedarach L (2003) Z. Naturforsch. C, 58, pp. 215-219
  • Barquero, A.A., Alché, L.E., Coto, C., Block of vesicular stomatitis virus endocytic and exocytic pathways by 1-cinnamoyl-3,11-dihydroxymeliacarpin, a tetranortriterpenoid of natural origin (2004) J. Gen. Virol., 85, pp. 483-493
  • Barquero, A.A., Michelini, F.M., Alché, L.E., 1-Cinnamoyl-3,11-dihydroxymeliacarpin is a natural bioactive compound with antiviral and nuclear factor-kappaB modulating properties (2006) Biochem. Biophys. Res. Commun., 344, pp. 955-962
  • Biswas, P.S., Rouse, B.T., Early events in HSV keratitis - setting the stage for a blinding disease (2005) Microbes Infect., 7, pp. 799-810
  • Biswas, P.S., Banerjee, K., Kinchington, P.R., Rouse, B.T., Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection (2006) Exp. Eye Res., 82, pp. 46-54
  • Bueno, C.A., Barquero, A.A., Di Cónsoli, H., Maier, M.S., Alché, L.E., A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent (2009) Virus Res., 141, pp. 47-54
  • Bueno, C.A., Alché, L.E., Barquero, A.A., 1-Cinnamoyl-3,11-dihydroxymeliacarpin delays glycoprotein transport restraining virus multiplication without cytotoxicity (2010) Biochem. Biophys. Res. Commun., 393, pp. 32-37
  • Carrasco, M.A., Subconjunctival bevacizumab for corneal neovascularization in herpetic stromal keratitis (2008) Cornea, 27, pp. 743-745
  • Cook, K.M., Figg, W.D., Angiogenesis inhibitors: current strategies and future prospects (2010) CA Cancer J. Clin., 60, pp. 222-243
  • Davel, L.E., Rimmaudo, L., Español, A., De La Torre, E., Jasnis, M.A., Ribeiro, M.L., Gotoh, T., Sales, M.E., Different mechanisms lead to the angiogenic process induced by three adenocarcinoma cell lines (2004) Angiogenesis, 7, pp. 45-51
  • De Luisi, A., Mangialardi, G., Ria, R., Acuto, G., Ribatti, D., Vacca, A., Anti-angiogenic activity of carebastine: a plausible mechanism affecting airway remodelling (2009) Eur. Respir. J., 34, pp. 958-966
  • Denizot, F., Lang, R., Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability (1986) J. Immunol. Methods, 89, pp. 271-277
  • Duan, R., de Vries, R.D., Osterhaus, A.D., Remeijer, L., Verjans, G.M., Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis (2008) J. Infect. Dis., 198, pp. 659-663
  • Ebrahem, Q., Minamoto, A., Hoppe, G., Anand-Apte, B., Sears, J., Triamcinolone acetonide inhibits IL-6 and VEGF-induced angiogenesis downstream of the IL-6 and VEGF receptors (2006) Invest. Ophthalmol. Vis. Sci., 47, pp. 4935-4941
  • Fujita, S., Saika, S., Kao, W., Fujita, K., Miyamoto, T., Ikeda, K., Nakajima, Y., Ohnishi, Y., Endogenous TNFalpha suppression of neovascularization in corneal stroma in mice (2007) Invest. Ophthalmol. Vis. Sci., 48, pp. 3051-3055
  • Hashizume, M., Hayakawa, N., Suzuki, M., Mihara, M., IL-6/sIL-6R trans-signalling, but not TNF-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system (2009) Rheumatol. Int., 29, pp. 1449-1454
  • He, M.F., Liu, L., Ge, W., Shaw, P.C., Jiang, R., Wu, L.W., But, P.P., Antiangiogenic activity of Tripterygium wilfordii and its terpenoids (2009) J. Ethnopharmacol., 121, pp. 61-68
  • Knickelbein, J.E., Hendricks, R.L., Charukamnoetkanok, P., Management of herpes simplex virus stromal keratitis: an evidence-based review (2009) Surv. Ophthalmol., 54, pp. 226-234
  • Lin, C.M., Chang, H., Chen, Y.H., Li, S.Y., Wu, I.H., Chiu, J.H., Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1 (2006) Int. Immunopharmacol., 6, pp. 1690-1698
  • Pifarré, M.P., Berra, A., Coto, C.E., Alché, L.E., Therapeutic action of meliacine, a plant-derived antiviral, on HSV-induced ocular disease in mice (2002) Exp. Eye Res., 75, pp. 327-334
  • Radtke, S., Wüller, S., Yang, X., Lippok, B.E., Mütze, B., Mais, C., de Leur, H.S., Hermanns, H.M., Cross-regulation of cytokine signaling: pro-inflammatory cytokines restrict IL-6 signaling through receptor internalization and degradation (2010) J. Cell Sci., 123, pp. 947-959
  • Urtreger, A., Ladeda, V., Puricelli, L., Rivelli, A., Vidal, M., Delustig, E., Joffe, E., Modulation of fibronectin expression and proteolytic activity associated with the invasive and metastatic phenotype in two new murine mammary tumor cell lines (1997) Int. J. Oncol., 11, pp. 489-496
  • Yeung, S.N., Lichtinger, A., Kim, P., Amiran, M.D., Slomovic, A.R., Combined use of subconjunctival and intracorneal bevacizumab injection for corneal neovascularization (2011) Cornea, 30, pp. 1110-1114
  • Zheng, M., Schwarz, M.A., Lee, S., Kumaraguru, U., Rouse, B.T., Control of stromal keratitis by inhibition of neovascularization (2001) Am. J. Pathol., 159, pp. 1021-1029
  • Zheng, M.E., Deshpande, S., Lee, S., Ferrara, N., Rouse, B.T., Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic stromal keratitis (2001) J. Virol., 75, pp. 9828-9835


---------- APA ----------
Bueno, C.A., Lombardi, M.G., Sales, M.E. & Alché, L.E. (2012) . A natural antiviral and immunomodulatory compound with antiangiogenic properties. Microvascular Research, 84(3), 235-241.
---------- CHICAGO ----------
Bueno, C.A., Lombardi, M.G., Sales, M.E., Alché, L.E. "A natural antiviral and immunomodulatory compound with antiangiogenic properties" . Microvascular Research 84, no. 3 (2012) : 235-241.
---------- MLA ----------
Bueno, C.A., Lombardi, M.G., Sales, M.E., Alché, L.E. "A natural antiviral and immunomodulatory compound with antiangiogenic properties" . Microvascular Research, vol. 84, no. 3, 2012, pp. 235-241.
---------- VANCOUVER ----------
Bueno, C.A., Lombardi, M.G., Sales, M.E., Alché, L.E. A natural antiviral and immunomodulatory compound with antiangiogenic properties. Microvasc. Res. 2012;84(3):235-241.