Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea

Abstract

Aim: To study whether epigallocatechin gallate (EGCG), a green tea-derived polyphenol, exerted anti-influenza A virus activity in vitro and in vivo. Methods: Madin-Darby canine kidney (MDCK) cells were tested. The antiviral activity of EGCG in the cells was determined using hemagglutination assay and qPCR. Time of addition assay was performed to determine the kinetics of inhibition of influenza A by EGCG. The level of reactive oxygen species (ROS) were determined with confocal microscopy and flow cytometry. BALB/c mice were treated with EGCG (10, 20 or 40 mg·kg -1 ·d -1 , po) for 5 d. On the 3rd d of the treatment, the mice were infected with influenza A virus. Histopathological changes, lung index and virus titers in the lungs were determined. Results: Treatment of influenza A-infected MDCK cells with EGCG (1.25-100 nmol/L) inhibited influenza A replication in a concentration-dependent manner (the ED 50 value was 8.71±1.11 nmol/L). Treatment with EGCG (20 nmol/L) significantly suppressed the increased ROS level in MDCK cells following influenza A infection. In BALB/c mice infected with influenza virus, oral administration of EGCG (40 mg·kg -1 ·d -1 ) dramatically improved the survival rate, decreased the mean virus yields and mitigated viral pneumonia in the lungs, which was equivalent to oral administration of oseltamivir (40 mg·kg -1 ·d -1 ), a positive control drug. Conclusion:The results provide a molecular basis for development of EGCG as a novel and safe chemopreventive agent for influenza A infection.

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

“…Following infection, the process of influenza replication can induce intracellular ROS in host cells [57,58], which could contribute to oxidative damage to the host genome. Indeed, ectopic expression of influenza matrix (M2) protein alone in human lung epithelial cell lines (A549 and H441) is sufficient to elevate intracellular and mitochondrial reactive oxygen species [51].…”

Pyrrolidine dithiocarbamate inhibits enterovirus 71 replication by down-regulating ubiquitin–proteasome system

“…Inhibited production of intracellular antioxidant glutathione (GSH) through the treatment of buthionine sulfoximine increased HIV yield of the infected cells (Savarino et al, 2009). In addition, the application of antioxidant showed dose-dependent antiviral effects on cultured cells or patients infected with HIV or influenza virus (Fraternale et al, 2008;Kash et al, 2014;Ling et al, 2012;Spada et al, 2002;Vlahos et al, 2012). To demonstrate whether or not targeting ROS alone could suppress the replication of EV71, cells were pretreated with PDTC two hours before EV71 infection and then grown in the media with no PDTC supplement.…”

Antiviral effects of green tea (<i>Camellia sinensis</i>) against pathogenic viruses in human and animals (a mini-review)

“…In Madin Durby Canine Kidney (MDCK) cells, EGCG at 20 nmol/l suppressed the level of reactive oxygen following influenza A infection (Ling et al 2012). The green tea extract inhibited the replication of influenza viruses by preventing acidification of intracellular compartment, such as lysosomes and endosomes (Lee et (Sahaa et al 2010).…”