Effect of resveratrol on herpes simplex virus vaginal infection in the mouse

• Published in: Antiviral research 2005-09, Vol.67 (3), p.155-162
• Main Authors: Docherty, John J., Fu, Ming Ming, Hah, Jennifer M., Sweet, Thomas J., Faith, Seth A., Booth, Tristan
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; Drug Evaluation, Preclinical; Female; Herpes Genitalis - drug therapy; Herpes Genitalis - pathology; Herpes Genitalis - virology; Herpes simplex virus; Herpes simplex virus 1; Herpes simplex virus 2; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - physiology; Herpesvirus 2, Human - drug effects; Herpesvirus 2, Human - isolation & purification; Herpesvirus 2, Human - physiology; Medical sciences; Mice; Mouse; Pharmacology. Drug treatments; Placebos; Resveratrol; Stilbenes - administration & dosage; Stilbenes - pharmacology; Stilbenes - therapeutic use; Survival Analysis; Vaginal Diseases - drug therapy; Vaginal Diseases - virology; Viral Plaque Assay; Virus Replication - drug effects; Vitaceae
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2005.06.008

Resveratrol (3,5,4′-trihydroxystilbene) is a natural component of certain foods, such as grapes, that, when topically applied, has been shown to limit HSV-1 lesion formation in the skin of mice [Antiviral Res. 61:19–26, 2004]. To determine if it is active on genital HSV infection, the vagina of mice were infected with HSV-2 or HSV-1 and treated with a cream formulation of resveratrol. Mice were evaluated daily for extravaginal disease and vaginal swabs were taken regularly and assayed for infectious virus. Initial studies demonstrated that 19% resveratrol cream administered intravaginally five times a day for 5 days beginning 1 h after infection significantly reduced HSV-2 replication beginning on day 1 of infection and prevented extravaginal disease when compared to animals treated with placebo. When resveratrol was tested at a concentration of 6.25% and 12.5% administered five times a day, 6.25% limited virus replication only on day 1 and delayed development of extravaginal disease by 1 day. However, 12.5% resveratrol inhibited HSV-2 replication beginning on day 1 and abolished extravaginal disease. If the number of applications per day was reduced to three for 5 days, 12.5% resveratrol inhibited HSV-2 replication only on day 1, while 19% resveratrol inhibited it throughout the 9-day assay period. When the animals with three treatments per day were examined for extravaginal disease, it was found that 12.5% resveratrol was ineffective when compared to placebo, while animals treated with 19% resveratrol did not exhibit extravaginal disease. When treatment was delayed 6 h, 12.5% resveratrol did not inhibit HSV-2 replication or extravaginal lesion formation, but 19% resveratrol did. When resveratrol was used to treat vaginal HSV-1 infection, it was found that 12.5% resveratrol did not limit replication or prevent extravaginal lesion formation. In contrast, 19% resveratrol did significantly limit vaginal HSV-1 replication and reduced extravaginal lesion formation, but the latter was not significant. Mortality rates in placebo-treated animals was 37%, 6.25% resveratrol-treated animals was 40%, 12.5% resveratrol-treated animals was 24%, and 19% resveratrol-treated animals was 3%. Collectively, these results demonstrate that resveratrol cream inhibits or reduces HSV replication in the vagina of mice and limits extravaginal disease.