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

John J Docherty, Ming Ming Fu, Jennifer M Hah, Thomas J Sweet, Seth A Faith, Tristan Booth
Author Information
  1. John J Docherty: Department of Microbiology/Immunology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, Rootstown, OH 44272, USA. jjd@neoucom.edu

Abstract

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 1h 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 6h, 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.

MeSH Term

Animals
Antiviral Agents
Drug Evaluation, Preclinical
Female
Herpes Genitalis
Herpesvirus 1, Human
Herpesvirus 2, Human
Mice
Placebos
Resveratrol
Stilbenes
Survival Analysis
Vaginal Diseases
Viral Plaque Assay
Virus Replication

Chemicals

Antiviral Agents
Placebos
Stilbenes
Resveratrol

Word Cloud

Created with Highcharts 10.0.0resveratrolextravaginaldayreplicationdiseaseanimals125%19%infectionHSV-21HSV-1lesionformationvaginal5limitmicetreatedcreamvirusbeginningreduced625%inhibitedresveratrol-treatedHSVvaginaadministeredfivetimesdayssignificantlycomparedplacebodelayedperthreefoundResveratrol34'-trihydroxystilbenenaturalcomponentcertainfoodsgrapestopicallyappliedshownskin[AntiviralRes61:19-262004]determineactivegenitalinfectedformulationMiceevaluateddailyswabstakenregularlyassayedinfectiousInitialstudiesdemonstratedintravaginally1hpreventedtestedconcentrationlimiteddevelopmentHoweverabolishednumberapplicationsthroughout9-dayassayperiodtreatmentsexaminedineffectiveexhibittreatment6hinhibitusedtreatpreventcontrastlattersignificantMortalityratesplacebo-treated37%40%24%3%CollectivelyresultsdemonstrateinhibitsreduceslimitsEffectherpessimplexmouse

Similar Articles

Cited By