Polygonum cuspidatum and Its Active Components Inhibit Replication of the Influenza Virus through Toll-Like Receptor 9-Induced Interferon Beta Expression

Abstract

Influenza virus infection is a global public health issue. The effectiveness of antiviral therapies for influenza has been limited by the emergence of drug-resistant viral strains. Therefore, there is an urgent need to identify novel antiviral therapies. Here we tested the effects of 300 traditional Chinese medicines on the replication of various influenza virus strains in a lung cell line, A549, using an influenza-specific luciferase reporter assay. Of the traditional medicines tested, Polygonum cuspidatum (PC) and its active components, resveratrol and emodin, were found to attenuate influenza viral replication in A549 cells. Furthermore, they preferentially inhibited the replication of influenza A virus, including clinical strains isolated in 2009 and 2011 in Taiwan and the laboratory strain A/WSN/33 (H1N1). In addition to inhibiting the expression of hemagglutinin and neuraminidase, PC, emodin, and resveratrol also increased the expression of interferon beta (IFN-β) through Toll-like receptor 9 (TLR9). Moreover, the anti-viral activity of IFN-β or resveratrol was reduced when the A549 cells were treated with neutralizing anti-IFN-β antibodies or a TLR9 inhibitor, suggesting that IFN-β likely acts synergistically with resveratrol to inhibit H1N1 replication. This potential antiviral mechanism, involving direct inhibition of virus replication and simultaneous activation of the host immune response, has not been previously described for a single antiviral molecule. In conclusion, our data support the use of PC, resveratrol or emodin for inhibiting influenza virus replication directly and via TLR-9–induced IFN-β production.

Screening for Anti‐Influenza Actives of Prefractionated Traditional Chinese Medicines

“…Interestingly, it was elucidated previously that the antiviral effect of Polygonum cuspidatum is associated with active compounds such as resveratrol and emodin, which inhibit the replication of influenza H1N1 virus directly by inducing IFN- β [ 28 ]. However, Magnolia officinalis contains polyphenolic compounds that play a protective role in influenza virus-infected mice [ 29 ].…”

Protective effects of Yinhuapinggan granule on mice with influenza viral pneumonia

“…Glycyrrhizin, which is an active component of Glycyrrhizae Radix, may protect mice infected with lethal doses of influenza virus through the induction of IFN-γ production by T cells [59], and has been reported to inhibit influenza A virus uptake into the cell [30]. Further, the main component of Polygoni Cuspidati Rhizoma, emodin, inhibits the replication of influenza virus H1N1 in A549 cells [32]. So, we hypothesize that chlorogenic acid, glycyrrhizin and emodin may be the active components of YHPG against influenza virus.…”

BIOLOGICALLY ACTIVE COMPOUNDS OF KNOTWEED (Reynoutria spp.)

“…Emodin also inhibits mutagenicity of 1-nitropyrene, a known mutagen, in a dose-dependent fashion by acting as a blocking and/or suppressing agent to reduce the direct-acting mutagenicity of 1-nitropyrene [82]. Emodin exhibits also antibacterial and antiviral effect, including anti-MRSA activity [83][84][85].…”