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Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend

Purpose: To compare three fractions of a medicinal mushroom blend (MMB),
MyCommunity, on immune-activation, inflammation-regulation, and induction of biomarkers
involved in regenerative functions.
Methods: A seventeen-species MMB was sequentially extracted: first, saline solution at
ambient temperature, followed by re-extraction of the solids in ethanol, and finally resuspension
of the homogenized ethanol-insoluble solids in cell-culture media. Fractions were tested
on peripheral blood mononuclear cells from three healthy donors. Immunostaining, flowcytometry,
and Luminex protein-arrays measured immune-cell activation and cytokine
response. Dose-responses for induction of the CD69 early activation marker and individual
cytokine and growth-factor responses for each donor were evaluated. The CD69 and the
combined cytokine and growth-factor results were subjected to Non-metric Multidimensional
Scaling (NMDS) and multivariate ordination to aid interpretation of the aggregate immune
response and pairwise permutational MANOVA on a distance-matrix to evaluate statistical
differences between treatments on pooled data from all donors.
Results: Differential effects were induced by water-soluble, ethanol-soluble, and insoluble
immunomodulatory compounds of the MMB. The aqueous and ethanol fractions upregulated
expression of CD69 on all tested cell types. Monocyte-activation was correlated with the
ethanol fraction, while NKT and non-NK non-T cell-activation was more closely correlated
with the aqueous fraction. The solid fraction was the most potent inducer of Tumor Necrosis
Factor-α, as well as the anti-viral cytokines interferon-γ, MCP-1 (CCL-2), MIP-1α (CCL-3),
and MIP-1β (CCL-4), and induced G-CSF and b-FGF—growth-factors involved in regenerative
functions—and the anti-inflammatory cytokine IL-1ra.
Conclusion: The aqueous, ethanol, and insoluble compounds within MMB induced differential
immune-activating, anti-inflammatory, and regenerative effects. This in vitro data suggests that,
upon consumption,MMB may induce a concerted series of immunomodulatory events based on
the differential solubility and bioavailability of the active constituents. These differential
responses support both immune-activation and resolution of the host defense-induced inflammatory
reactions, thus assisting a post-response return to homeostasis.
Keywords: CD69, cytokines, growth factors, anti-viral peptides, medicinal mushrooms,
mycelium, immune support, redundancy analysis, rda, multivariate ordination.

Davis, R., Taylor, A., Nally, R., Benson, K. F., Stamets, P., & Jensen, G. S. (2020). Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend. Journal of Inflammation Research, Volume 13, 117-131. doi:10.2147/jir.S229446