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

• Published in: PloS one Vol. 14; no. 11; p. e0224740
• Main Authors: Mallard, Brody, Leach, David N, Wohlmuth, Hans, Tiralongo, Joe
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.11.2019; Public Library of Science (PLoS)
• Subjects: Alternative medicine; Beta glucan; beta-Glucans - metabolism; Biology and Life Sciences; Cancer; Cytokines; Cytokines - metabolism; Drug Synergism; Ganoderma lucidum; Gene expression; Glucan; Glucans; Glucose; Grifola - chemistry; Human behavior; Humans; Immune system; Immunologic Factors - pharmacology; Immunomodulation; Inhibitory Concentration 50; Interleukin 10; Interleukin 6; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Medicine and Health Sciences; Mushrooms; Natural products; Polysaccharides; Reishi - chemistry; Saccharides; Shiitake Mushrooms - chemistry; Signal transduction; Stimulators; Synergistic effect; Tumor necrosis factor; Tumor necrosis factor-α; β-Glucan; Queensland Australia; Australia; New South Wales Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224740

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.