RT Journal Article
SR Electronic
T1 Biological Characterization of Eugeniin as an Anti-Herpes Simplex Virus Type 1 Compound in Vitro and in Vivo
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 372
OP 379
VO 297
IS 1
A1 Masahiko Kurokawa
A1 Toyoharu Hozumi
A1 Minako Tsurita
A1 Shigetoshi Kadota
A1 Tsuneo Namba
A1 Kimiyasu Shiraki
YR 2001
UL http://jpet.aspetjournals.org/content/297/1/372.abstract
AB Eugeniin exhibits antiviral activity against acyclovir and phosphonoacetic acid (PAA)-resistant herpes simplex virus type 1 (HSV-1) as well as the wild-type HSV-1 in vitro. In this study, we characterized the biological activity of eugeniin in cutaneously HSV-1-infected mice and its interaction with HSV-1 DNA polymerase. The oral and intraperitoneal administrations of eugeniin at 0.3 mg/kg showed similar therapeutic efficacy in retarding the development of skin lesions of HSV-1-infected mice. The two routes of administration at 6 or 50 mg/kg significantly prolonged the mean survival times and/or reduced mortality without toxicity. The oral administration of eugeniin at 50 mg/kg reduced virus yields in the skin and brain of infected mice. Thus, the therapeutic efficacy of oral administration at the various doses of eugeniin was similar to that of intraperitoneal administration, suggesting that the oral bioavailability of eugeniin was high with respect to absorption. Furthermore, the anti-HSV-1 activity of eugeniin was characterized by isobolograms analyzing its combined effects with acyclovir or PAA in HSV-1-infected Vero cells. Eugeniin enhanced the anti-HSV-1 activity of acyclovir but was suggested to be antagonistic with PAA. The interaction of eugeniin and PAA on the activity of partially purified HSV-1 DNA polymerase suggested that eugeniin interacted with the polymerase in the vicinity of PAA-binding site. Thus, eugeniin showed different anti-HSV-1 action from acyclovir and PAA and therapeutic anti-HSV-1 activity in mice. The American Society for Pharmacology and Experimental Therapeutics