THE INHIBITORY ACTIONS OF HOUTTUYNIA CORDATA AQUEOUS EXTRACT ON DENGUE VIRUS AND DENGUE-INFECTED CELLS VIJITTRA LEARDKAMOLKARN 1,6 , WIPAWAN SIRIGULPANIT 1 , CHAYAKOM PHURIMSAK 2 , SUPEECHA KUMKATE 3 , LUKANA HIMAKOUN 4 and BUNGORN SRIPANIDKULCHAI 5 1 Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand 2 Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok 10400, Thailand 3 Department of Biology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand 4 Department Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand 5 Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand 6 Corresponding author. TEL: +66-2201-5405; FAX: +66-2354-7168; EMAIL: scvlk@mahidol.ac.th Accepted for Publication June 2, 2010 doi:10.1111/j.1745-4514.2010.00514.x ABSTRACT The antiviral activities of Houttuynia cordata (H. cordata) aqueous extract against dengue virus serotype 2 (DEN-2), strain 16681, were evaluated in this study. The results showed that pre- and post-incubation of H. cordata extract (10–100 mg/mL) with HepG2 cells significantly reduced intracellular DEN-2 RNA production corre- lating with the decrease in dengue protein expression. In the direct blocking mode, the extract bound with DEN-2 and strongly inhibited the intracellular viral RNA replication with an effective dose (EC50) of 0.8 mg/mL. Concentrations as low as 10–40 mg/mL of H. cordata extract also exhibited protective effect on virion release from infected LLC-MK2 cells. High-performance liquid chromatography analysis of H. cordata extract indicated that hyperoside was the predominant bioactive com- pound, and was likely to play a role in this inhibition. The extract was also shown to have no genotoxic effect on human blood cells. PRACTICAL APPLICATIONS Houttuynia cordata is recognized as medicinal vegetable consumed by people in East and Southeast Asia. It has multilateral activities in health promotion and regulation of inflammatory reactions induced by several pathogens. Dengue viral infection is a global health problem since licensed vaccines or specific antiviral drug treatments are not yet available. The current study provides scientific data to support the phy- tomedicinal properties of H. cordata aqueous extract on anti-dengue virus in three modes of action (prevention, treatment and virucidal). A major constituent in the extract, hyperoside, seems to be the bioactive compound effectively acting against dengue infection. H. cordata aqueous extract was shown to be nontoxic and hypero- side may be considered a lead compound possessing drug potential for further development. INTRODUCTION Houttuynia cordata Thunb (Saururaceae; H. cordata) com- monly known as “Pak Kan Thong” in Thai, is a popular side- dish vegetable, which is consumed in the Northern and Eastern regions of Thailand. Its medicinal properties in the treatment of chronic sinusitis and allergy are accepted in several Asian countries including Korea, Taiwan and China (Lu et al. 2006a; Ng et al. 2007; Han et al. 2009). Recent inves- tigations have documented H. cordata for treatment of a number of physiological and immunological disorders, such as anti-allergy (Li et al. 2005; Han et al. 2009), antioxidant (Chen et al. 2003; Park et al. 2005; Kusirisin et al. 2009) and anti-leukemia (Chang et al. 2001). The anti-inflammatory Journal of Food Biochemistry ISSN 1745-4514 86 Journal of Food Biochemistry 36 (2012) 86–92 © 2011 Wiley Periodicals, Inc.