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, 1 Tomohiko Urushisaki, 1 Mayuko Fukuoka, 2, 3 Junji Hosokawa-Muto, 4, 5 Taketoshi Hata, 1 Yumiko Okuda, 4 Sachie Hori, 4 Shigemi Tazawa, 1 Yoko Araki, 1 and Kazuo Kuwata 2, 3, 4 *

1Nagaragawa Research Center, API Co., Ltd., 692-3 Nagara, Gifu 502-0071, Japan

2United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

3CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan

4Center for Emerging Infectious Diseases, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan

5First Department of Forensic Science, National Research Institute of Police Science, 6-3-1 Kashiwanoha, Kashiwa, Chiba 277-0882, Japan

*Kazuo Kuwata: Email: kuwata@gifu-u.ac.jp

Academic Editor: Vincenzo De Feo

Received May 12, 2011; Revised July 4, 2011; Accepted July 4, 2011.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 200mg/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 50mg/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.

 

 

* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.