A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent.
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-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA purification, displays anti-herpetic activity and impedes nuclear factor kappaB (NF-kappaB) 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-kappaB 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-kappaB translocation to the nucleus, leading to a decrease in IL-6 production. Besides, CDM seemed to modulate IL-6 and TNF-alpha responses in macrophages, whether they were infected with HSV-1 or stimulated with LPS. However, CDM did not affect NF-kappaB activation in these cells, suggesting that an alternative NF-kappaB cell signaling pathway would be involved in the modulation of 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.
Bueno
Carlos A
CA
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
Barquero
Andrea A
AA
Di Cónsoli
Hernán
H
Maier
Marta S
MS
Alché
Laura E
LE
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D036701:Limonins / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D031586:Melia azedarach / Q000737:chemistry*; D051379:Mice
D000998:Antiviral Agents; D016207:Cytokines; D036701:Limonins