Abstract

Influenza is a major cause of respiratory tract infection. Although most cases do not require further hospitalization, influenza periodically causes epidemics in humans that can potentially infect and kill millions of people. To countermeasure this threat, new vaccines need to be developed annually to match emerging influenza viral strains with increased resistance to existing vaccines. Thus, there is a need for finding and developing new anti-influenza viral agents as alternatives to current treatments. Here, we tested the antiviral effects of an extract from the stems and roots of Salacia reticulata (SSRE), a plant rich in phytochemicals, such as salacinol, kotalanol, and catechins, on H1N1 influenza virus-infected mice. Following oral administration of 0.6 mg/day of SSRE, the incidence of coughing decreased in 80% of mice, and only one case of severe pulmonary inflammation was detected. Moreover, when compared with mice given Lactobacillus casei JCM1134, a strain previously shown to help increase in vitro natural killer (NK) cell activity, SSRE-administered mice showed greater and equal NK cell activity in splenocytes and pulmonary cells, respectively, at high effector cell:target cell ratios. Next, to test whether or not SSRE would exert protective effects against influenza in the absence of gut microbiota, mice were given antibiotics before being inoculated influenza virus and subsequently administered SSRE. SSRE administration induced an increase in NK cell activity in splenocytes and pulmonary cells at levels similar to those detected in mice not treated with antibiotics. Based on our results, it can be concluded that phytochemicals in the SSRE exerted protective effects against influenza infection putatively via modulation of the immune response, including enhancement of NK cell activity, although some protective effects were not necessarily through modulation of gut microbiota. Further investigation is necessary to elucidate the molecular mechanisms underlying the protective effects of SSRE against influenza infection.

Highlights

  • Influenza is a leading cause of respiratory tract infection [1]

  • We investigated the effect of stems and roots of Salacia reticulata (SSRE) on natural killer (NK) cell activity in spleen and lung cells of mice given a powerful antibiotic cocktail and inoculated with H1N1 influenza virus

  • We observed that administration of a bark and root extract from S. reticulata triggered an ­antiviral immune response in rat ileum involving Cd26 and IgG2a [30]

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Summary

Introduction

Influenza is a leading cause of respiratory tract infection [1]. Influenza viruses are categorized as A, B, and C [2], and influenza A virus can be further subtyped as H3N2, H2N2, and H1N1. Since toxicity receptors NKp46 and NKp44 on human NK cells readily identify hemagglutinin and neuraminidase on the surface of influenza virus, NK cells alone have the potential of destroying infected cells [9]. Impaired cytotoxicity and depletion of NK cells that lead to higher morbidity and mortality rates are often observed in influenza virus-infected subjects for reasons not yet fully understood [10]. Every year, new vaccines need to be developed to match emerging influenza viral strains with increased resistance to existing vaccines [11, 12]. This challenge highlights the need for finding and developing new antiviral agents as alternatives to those currently available

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