A natural antiviral tetranortriterpenoid with immunodulatory properties

PETRERA, E.; BUENO, C.A.; BARQUERO, A.A.; COTO, C.E.; ALCHÉ, L.E.

Mar del Plata, Buenos Aires, Argentina

Congreso; XXLIII Reunión anual SAIB; 2007

SAIB

The 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), isolated from purified leaf extracts of Melia azedarach L., exhibits anti-HSV-1 activity, inhibits HSV-1-induced NF-kB translocation and increases TNF-alpha production in an infected macrophage cell line (J774A.1). Also, in the presence of CDM, murine peritoneal macrophages stimulated with HSV-2 increment TNF-alpha secretion. To extend our understanding about CDM properties we investigated its effect on NF-kB activation and cytokine secretion in J774A.1 cells and peritoneal macrophages induced with herpes viral and no-viral stimuli. Results showed that HSV-2 was not able to multiply in peritoneal macrophages, neither induced persistent NF-kB translocation nor IkB-alpha degradation, as determined by immunofluorescence and western blot assays, respectively. On the contrary, HSV-1 induced IkB-alpha degradation in infected J774A.1, which was prevented by CDM. Besides, the production of TNF-alpha in LPS-stimulated J774A.1 cells was strongly enhanced by CDM, as well as in peritoneal macrophages, as determined by a biological assay. Our data suggest that CDM would prevent NF-kB translocation induced by virus multiplication, as a consequence of its antiviral activity.  Furthermore, CDM could enhance TNF-alpha production regardless the stimuli involved. Taken together, this study shows that CDM exhibits immunomodulatory properties.