Abstract

BackgroundInfluenza infection is a major public health threat. The role of influenza A virus-induced inflammatory response in severe cases of this disease is widely recognized. Drug resistance and side effects of chemical treatments have been observed, resulting in increased interest in alternative use of herbal medications for prophylaxis against this infection.The South African medicinal plant, Rapanea melanophloeos (RM) (L.) Mez of the family Myrsinaceae was selected owing to its traditional use for the treatment of several diseases such as respiratory ailments and also previous preliminary studies of anti-influenza activity of its methanolic extract. The aim of this study was to investigate the immunomodulatory properties of a glycoside flavone isolated from RM against influenza A virus.MethodsThe non-cytotoxic concentration of the quercetin-3-O-α-L-rhamnopyranoside (Q3R) was determined by MTT assay and tested for activity against influenza A virus (IAV) in simultaneous, pre-penetration and post-penetration combination treatments over 1 h incubation on MDCK cells. The virus titer and viral load targeting NP and M2 viral genes were determined using HA and qPCR, respectively. TNF-α and IL-27 as pro- and anti-inflammatory cytokines were measured at RNA and protein levels by qPCR and ELISA, respectively.ResultsQuercetin-3-O-α-L-rhamnopyranoside at 150 μg/ml decreased the viral titer by 6 logs (p < 0.01) in the simultaneous procedure. The NP and M2 genes copy numbers as viral target genes, calculated based on the Ct values and standard formula, significantly decreased in simultaneous treatment (p < 0.01). The expression of cytokines was also considerably affected by the compound treatment.ConclusionsThis is the first report of quercetin-3-O-α-L-rhamnopyranoside from RM and its immunomodulatory properties against influenza A virus. Further research will focus on detecting the specific mechanism of virus-host interactions.

Highlights

  • Influenza infection is a major public health threat

  • A search in the Dictionary of Natural Products [25] and comparing the spectroscopic and MS data with the literature confirmed the structure as quercetin-3-O-α-L-rhamnopyranoside (Fig. 1b)

  • Anecdotal evidence supports the traditional use of Rapanea melanophloeos for the treatment of several respiratory ailments, and in our previous research we studied the methanolic extract this plant and showed its efficacy against influenza A virus [18]

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Summary

Introduction

Influenza infection is a major public health threat. The role of influenza A virus-induced inflammatory response in severe cases of this disease is widely recognized. Drug resistance and side effects of chemical treatments have been observed, resulting in increased interest in alternative use of herbal medications for prophylaxis against this infection. The acquisition of resistance to chemical drugs such as M2 and NA inhibitors, [3] mainly due to antigenic shifts and drifts, is a potential problem [2, 3]. This issue has led to the caution from the Centers for Disease Control and Prevention (CDC) over the continued use of these drugs [4]. Studies to determine the chemical profile and composition of medicinal plants have revealed the complexity and variety of compounds all contributing to the various uses of plants in treating numerous diseases including life-threatening bacterial and viral diseases, and cancers [11]

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