Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice.
Oxyresveratrol, a major compound purified from Artocarpus lakoocha, a Thai traditional medicinal plant, was evaluated for its mechanism of action and therapeutic efficacy on cutaneous herpes simplex virus (HSV) infection in mice. The inhibitory concentrations for 50% HSV-1 plaque formation of oxyresveratrol, three clinical isolates, thymidine kinase (TK)-deficient and phosphonoacetic acid (PAA)-resistant HSV-1 were 19.8, 23.3, 23.5, 24.8, 25.5 and 21.7microg/ml, respectively. Oxyresveratrol exhibited the inhibitory activity at the early and late phase of viral replication and inhibited the viral replication with pretreatment in one-step growth assay of HSV-1 and HSV-2. Oxyresveratrol inhibited late protein synthesis at 30microg/ml. The combination of oxyresveratrol and acyclovir (ACV) produced synergistic anti-HSV-1 effect, as characterized by the isobologram of plaque inhibition. Mice orally treated with oxyresveratrol (500mg/kg/dose) dose at 8 h before and three times daily had significant delay in herpetic skin lesion development (P<0.05). Topical application of 30% oxyresveratrol ointment five times daily significantly delayed the development of skin lesions and protected mice from death (P<0.0001).
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Taksina
T
Chuanasa
Jurairatana
J
Phromjai
Vimolmas
V
Lipipun
Kittisak
K
Likhitwitayawuid
Mikiko
M
Suzuki
Pornpen
P
Pramyothin
Masao
M
Hattori
Kimiyasu
K
Shiraki
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D029586:Moraceae / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal / Q000737:chemistry; D012871:Skin Diseases / Q000188:drug therapy* / Q000821:virology; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use; D013785:Thailand; D016896:Treatment Outcome; D014709:Vero Cells; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D010936:Plant Extracts; D013267:Stilbenes; C034912:puag-haad