We have reported the isolation of the tetranortriterpenoid 1-cinnarnoyl-3,11-dihydroxymeliacarpin (CDM) from partially purified leaf extracts of Melia azedarach L. (MA) that reduced both, vesicular stomatitis virus (VSV) and Herpes simplex virus type 1 (HSV-1) multiplication. CDM blocks VSV entry and the intracellular transport of VSV-G protein, confining it to the Golgi apparatus, by pre- or post-treatment. respectively. Here, we report that HSV-1 glycoproteins were also confined to the Golgi apparatus independently of the nature of the host cell. Considering, that MA could be acting as an immunomodulator preventing the development of herpetic stromal keratitis in mice. we also examined all eventual effect of CDM on NF-kappa B signaling pathway. CDM is able to impede NF-kappa B activation in HSV-1-infected conjunctival cells and leads to the accumulation of p65 NF-kappa B subunit ill the cytoplasm of uninfected treated Vero cells. In conclusion. CDM is a pleiotropic agent that not only inhibits the Multiplication of DNA and RNA viruses by the same mechanism of action but also modulates the NF-kappa B signaling pathway. (c) 2006 Elsevier Inc. All rights reserved.