Abstract

A key characteristic of mushroom polysaccharides that elicit an immunomodulatory response is that they are rich in β-glucans and low in α-glucans. In this study we analysed nine commercially available preparations from three mushroom species, Reishi (Ganoderma lucidum), Shiitake (Lentinula edodes) and Maitake (Grifola frondosa), for β- and α-glucan content. Based on β- and α-glucan content we selected three extracts to combine into a formula and evaluated the ability of the individual extracts and formula to impact on the expression of cytokines IL-1α, IL-6, IL-10 and TNF-α in human macrophages with and without LPS stimulation. The majority of mushroom extracts and the formula were found to be highly potent immuno-stimulators possessing EC50 values lower than 100 μg/mL. Interestingly the mushroom formula had lower EC50 values in TNF-α expression from LPS stimulated macrophages compared to the individual extracts, suggesting a potential synergistic effect of the mushroom formula. A response additivity graph and curve-shift analysis illustrated that indeed the mushroom formula exhibited an immuno-stimulatory synergistic effect on the expression of the majority of cytokines evaluated in both LPS stimulated and non-stimulated human macrophages, with IL-10 having an antagonistic response. This study represents the first report of a synergistic immuno-modulatory response in human macrophages elicited from a mushroom formula rationally derived from β- and α-glucan content.

Highlights

  • Medicinal mushrooms possess a variety of bioactive compounds with immunomodulatory activities, such as polysaccharides, polysaccharopeptides, phenolic compounds, proteins, lipid components and terpenoids [1]

  • Synergistic immuno-modulatory activity of a medicinal mushroom formulation involved in the preliminary cytokine expression study design, preliminary data analysis, editing and revising of the manuscript, and decision to publish

  • The concept of synergy is well established in the natural products field, with for example synergy reported between plant natural products for the prevention and/or treatment of cancer [26, 27] and malaria [28], and between natural products and antibiotics for the treatment of infectious disease [29]

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Summary

Introduction

Medicinal mushrooms possess a variety of bioactive compounds with immunomodulatory activities, such as polysaccharides, polysaccharopeptides, phenolic compounds, proteins, lipid components and terpenoids [1]. BM and JT are employees of Griffith University and designed and conducted the cytokine expression analysis as well as the synergy analysis They acquired the cytokine expression data, analysed and interrupted the data, wrote, edited and revised the manuscript, and initiated the decision to publish. DNL and HW are employees of Integria Healthcare (Australia) Pty Ltd, which is the sponsor of MediHerb® Mushroom Forte. We confirm that this does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials

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