3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A Virus.

Tomoaki Takemura,Shigemi Tazawa,Yoko Araki,Yumiko Okuda,Mayuko Fukuoka,Kazuo Kuwata,Junji Hosokawa-Muto,Tomohiko Urushisaki,Sachie Hori,Taketoshi Hata

doi:10.1155/2012/946867

Abstract

Brazilian green propolis water extract (PWE) and its chemical components, caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA), act against the influenza A virus (IAV) without influencing the viral components. Here, we evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE (Brazilian green propolis ethanol extract) at a dose of 200 mg/kg was orally administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33. The lifetimes of the PWE-treated mice were significantly extended compared to the untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE, at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased. These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique mechanism of anti-influenza viral activity, that is, enhancing viral clearance by increasing TRAIL.

Highlights

Influenza is a common infectious disease, and various antiinfluenza drugs are already on the market
We found that the amount of tumor necrosis factor-related apoptosisinducing ligand (TRAIL) mRNA in the mice that were administered 3,4-diCQA was significantly increased compared to the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased
To obtain insights into the mechanism of the antiviral effects of propolis water extract (PWE) and PEE, we examined tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and influenza A virus (IAV) hemagglutinin (HA) gene expression in the lungs, because it has been reported that the ethanol extract of Polish propolis has antitumor activity via TRAIL enhancement [32]

Summary

Introduction

Influenza is a common infectious disease, and various antiinfluenza drugs are already on the market. Oseltamivir is one of the most popular antiinfluenza drugs, many resistant strains have already been discovered [4, 5]. The resistant strains that have been found to date are not yet pandemic. We need to carefully monitor the emergence and prevalence of new strains with pandemic characteristics, such as the H1N1 pandemic with drug resistance, which may occur because of the high incidence of mutations [6] and genomic rearrangements [7]. The discovery of novel anti-influenza agents that do not carry the risk of creating resistant strains would be urgently required

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Conclusion