Neospora caninum is an apicomplexan parasite associated with abortion in cattle worldwide. Apicidin, histone deacetylase (HDAC) inhibitor, has shown a broad spectrum of anti-protozoal activity against apicomplexan parasites. Cultured vero cells infected with N. caninum tachyzoites were treated with 0.5 microg/ml of depudecin, another known natural product isolated from Altermaria brassiciicola with anti-histone deacetylase activity, to examine the efficacy of depudecin against intracellular multiplication of N. caninum tachyzoite, using 15 ng/ml of apicidin as the control. Depudecin significantly inhibited the intracellular multiplication of N. caninum at a level similar to that of apicidin without exerting any cytotoxicity on the host vero cells. Acid/urea/Triton gel electrophoresis analysis show anti-parasitic activity of depudecin appears to be due to the inhibition of protozoal histone deacetylase, which induces hyperacetylation of histones in N. caninum.