Therapeutic action of meliacine, a plant-derived antiviral, on HSV-induced ocular disease in mice.

Ocular herpes simplex virus type-1 (HSV-1) infections remain an important cause of corneal disease which may result in a loss of vision. Meliacine (MA), an antiviral activity present in crude leaf extracts of Melia azedarach L. that inhibits HSV-1 multiplication in vitro, was studied in a murine herpetic stromal keratitis experimental model. Adult Balb/c mice were inoculated with HSV-1 at their corneas after abrasion. MA was administered topically three times a day for 3 consecutive days, beginning at 24 and 96 hr after infection. Infected animals treated or not with MA were monitored for the development of ocular disease by a binocular microscope for 16 days. MA significantly reduced the incidence and the severity of blepharitis, neovascularization and stromal keratitis with respect to untreated infected mice, regardless the schedule of treatment assayed. Histological examination of corneas from MA-treated animals revealed no tissue damage, whereas corneal samples from untreated infected mice showed inflammation, vascularization and necrosis. In uninfected mice treated with MA, we found no evidence of corneal damage and histopathological studies showed no changes in the corneas of these mice. Treatment with MA at 24 hours post-infection (h.p.i.) reduced viral multiplication in the eye by 1-1.5 orders of magnitude. Studies on latency revealed that MA sligthly affected the establishment of a latent infection. Thus, MA proved to exert an antiviral action on the development of herpetic stromal keratitis when supplied by post-treatment. Unexpectedly, treatment with MA after 96h.p.i prevented ocular disease, suggesting an in vivo immunomodulating activity of MA.