1-Cinnamoyl-3,11-dihydroxymeliacarpin is a natural bioactive compound with antiviral and nuclear factor-kappaB modulating properties.
We have reported the isolation of the tetranortriterpenoid 1-cinnamoyl-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 an eventual effect of CDM on NF-kappaB signaling pathway. CDM is able to impede NF-kappaB activation in HSV-1-infected conjunctival cells and leads to the accumulation of p65 NF-kappaB subunit in 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-kappaB signaling pathway.
Barquero
Andrea A
AA
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, Piso 4to., Ciudad Universitaria, C1428BGA Buenos Aires, Argentina. alecab@qb.fcen.uba.ar
Michelini
Flavia M
FM
Alché
Laura E
LE
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D002460:Cell Line; D002522:Chlorocebus aethiops; D003228:Conjunctiva / Q000187:drug effects / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000254:growth & development*; D006801:Humans; D036701:Limonins / Q000008:administration & dosage*; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
C474472:1-cinnamoyl-3,11-dihydroxymeliacarpin; D000998:Antiviral Agents; D036701:Limonins; D016328:NF-kappa B