The Inhibitory Actions of Houttuynia Cordata Aqueous Extract on Dengue Virus and Dengue-Infected Cells

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 µg/mL) with HepG2 cells significantly reduced intracellular DEN‐2 RNA production correlating 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 µg/mL. Concentrations as low as 10–40 µg/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 compound, 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 phytomedicinal 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 hyperoside may be considered a lead compound possessing drug potential for further development.

Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses

“…Highperformance liquid chromatography of the aqueous extract revealed that hyperoside (compound 39) (Figure 6) is the major component of the extract, suggesting that this flavonoid plays an important role in DENV-2 inhibition. The aqueous extract had no toxic effects on human blood cells [53]. Figure 7 suggest that ajugasterone C (compound 42) is equipotent to 2´-Cmethylcytidine (positive control), with a better SI.…”

Anti-Viral Effects of Medicinal Plants in the Management of Dengue: A Systematic Review

“…Infection with one DENV serotype produces only specific antibody against that serotype. When antibody from the first infection is neutralized, secondary infections by other serotypes can cause more serious infection (Leardkamolkarn et al, 2012). Although DENV-2 is known to be more lethal than other serotypes (Goel et al, 2004), some studies have revealed that primary infection with DENV-1 or DENV-3 always results in more dangerous disease than infection with the other serotypes (Guzman and Isturiz, 2010;Tang et al, 2012).…”

Antiviral Activity of Thiazolide Derivatives Against Dengue Virus in Huh-7 Cell Line

“…Dengue was seen a 30-fold upsurge worldwide between 1960 and 2010 due to increased population growth rate, global warming, unplanned urbanization, inefficient mosquito control, frequent air travel, and lack of health care facilities (2)(3)(4)(5). Two and a half billion people reside in dengue-endemic regions and 400 million infections roughly occur per year, with a mortality rate surpassing 5% -20% in some areas (6,7). Dengue infection affects more than 100 countries, including European countries and the United States (USA) (7).…”

“…Nonstructural proteins are responsible for the replication of viral genome and evasion from host immunity. Many antiviral compounds have been reported to inhibit DENV replication in vitro and in vivo (6,11,12). However, no approved antiviral drug is yet available for the treatment of DENV infectious disease.…”