Microemulsion-based oxyresveratrol for topical treatment of herpes simplex virus (HSV) infection: physicochemical properties and efficacy in cutaneous HSV-1 infection in mice.

The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p < 0.05) compared with the untreated control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was as effective as 5% w/w of acyclovir cream, topically applied five times daily (p > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20-30% w/w was suitable for cutaneous HSV-1 mouse infection.

Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice.

Anti-herpes simplex virus (HSV) activities of oxyresveratrol in vitro and topical administration in cutaneous HSV-1 infection in mice were examined. The inhibitory concentrations for 50% plaque formation (IC(50)) of oxyresveratrol against HSV-1 clinical isolates and HSV-2 clinical isolates were 20.9-29.5 and 22.2-27.5 µg/ml, respectively. In topical administration in cutaneous HSV-1 infection in mice, 2.5%, 5%, 10% and 20% oxyresveratrol in cream vehicle applied three times daily for 7 days after infection were evaluated and 10% and 20% oxyresveratrol cream were significantly effective in delaying the development of skin lesions and protection from death (P < 0.01). The concentration of 10% oxyresveratrol in cream was significantly more effective than that of 30% oxyresveratrol in vaseline applied three times daily (P < 0.01). Oxyresveratrol cream at 20% was as effective as 5% ACV cream applied three times daily (P < 0.01). Both 10% and 20% oxyresveratrol cream were as effective as that of 5% ACV cream applied two times daily (P > 0.05). Therapeutic efficacy of oxyresveratrol in cream vehicle was dose-dependent and the maximum efficacy observed on day 6 after infection was shown at 10% oxyresveratrol in cream applied three times daily. The frequency of application of 10% oxyresveratrol cream at three, four and five times daily was as effective as that of 5% ACV cream applied five times daily (P > 0.05). These results demonstrated that topical administration of oxyresveratrol in novel cream vehicle reduced the concentration of oxyresveratrol to 10% and was suitable for cutaneous HSV infection.

Inhibitory activity of oxyresveratrol on wild-type and drug-resistant varicella-zoster virus replication in vitro.

The anti-herpes simplex virus (HSV) compound, oxyresveratrol, purified from a Thai traditional medicinal plant of Artocarpus lakoocha, was evaluated for its anti-varicella-zoster virus (VZV) activity. This compound exhibited IC(50) values (50%-inhibitory concentrations for virus plaque formation) of 12.82, 12.80, 12.99 and 12.82 microg/ml against wild type, thymidine kinase-deficient and two types of DNA polymerase mutants with acyclovir-resistance, respectively. Thus oxyresveratrol showed a broad spectrum of anti-VZV activity with a mechanism of action different from that of acyclovir.