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PLoS One. 2019 Nov 7;14(11):e0224740. doi: 10.1371/journal.pone.0224740. eCollection 2019.

Synergistic immuno-modulatory activity in human macrophages of a medicinal mushroom formulation consisting of Reishi, Shiitake and Maitake.

Author information

Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
Integria Healthcare, Eight Mile Plains, Queensland, Australia.
National Institute of Complementary Medicine, Western Sydney University, Penrith, New South Wales, Australia.
School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia.


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.

Conflict of interest statement

This research was sponsored by Integria Healthcare (Australia) Pty Ltd., and was conducted collaboratively with DNL and HW who are employees of Integria Healthcare (Australia) Pty Ltd. DNL and HW quantified the glucan levels in the mushroom extracts, were involved in the preliminary cytokine expression study design, preliminary data analysis, editing and revising of the manuscript, and decision to publish. 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. A patent application (International PCT Application No. PCT/AU2019/050295) based in part on these results has been filed by Integria Healthcare (Australia) Pty Ltd naming BM, DNL, HW and JT as inventors. 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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