A natural tetranortriterpenoid with immunomodulating properties as a potential anti HSV-agent

BUENO CARLOS; BARQUERO ANDREA A.; DI CÓNSOLI HERNÁN; MAIER MARTA S.; ALCHÉ, LAURA

VIRUS RESEARCH

ELSEVIER SCIENCE BV

Año: 2009 vol. 141 p. 47 - 54

0168-1702

Meliacine (MA) an antiviral principle present in partially purified leaf extracts of Melia azedarach L., prevents the development of herpetic stromal keratitis (HSK) in mice by diminishing the viral load in the eye and the severity of lesions caused by a virus-induced immunopathological reaction. The tetranortriterpenoid 1-cinammoyl-3,11-dihydroxymeliacarpin (CDM) obtained from MA purification, displays anti-herpetic activity and impedes nuclear faktor kB (NF-kB) activation in HSV-1 infected conjunctival cells.To extend our understanding about CDM biological properties, we investigated its anti-HSV-1 activity as well as the effect on NF-kB activation and cytokine secretion induced by viral (HSV-1) and no viral (LPS) stimuli in corneal cells and macrophages. CDM exerted a potent anti-HSV-1 effect on corneal cells and inhibited NF-kB translocation to the nucleus, leading to a decrease in IL-6 production. Besides, CDM seemed to modulate IL-6 and TNF-a responses in macrophages., whether they were infected with HSV-1 or stimulated with LPS. However, CDM did not affect NF-kB activation in these cells, suggesting that an alternative NF-kB cell signaling pathway could be involved in the modulation of the cytokine production. We conclude that, in addition to its antiviral effect, CDM would be acting as an immunomodulating compound which would be responsible for the improvement of murine HSK already reported.