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

Renee Davis,1 Alex Taylor,1 Regan Nally,1 Kathleen F Benson,2 Paul Stamets,1 Gitte S Jensen2 1Fungi Perfecti, Olympia, WA 98507, USA; 2NIS Labs, Klamath Falls, OR 97601, USACorrespondence: Gitte S JensenNIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, USATel +1 541 884-0112Fax +1403 441-5236Email...

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Autores principales:	Davis R, Taylor A, Nally R, Benson KF, Stamets P, Jensen GS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	cd69 cytokines growth factors anti-viral peptides medicinal mushrooms mycelium immune support redundancy analysis (rda) multivariate ordination Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/3e981e79452440eaa828421a7c0635c8
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spelling	oai:doaj.org-article:3e981e79452440eaa828421a7c0635c82021-12-02T09:55:58ZDifferential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend1178-7031https://doaj.org/article/3e981e79452440eaa828421a7c0635c82020-02-01T00:00:00Zhttps://www.dovepress.com/differential-immune-activating-anti-inflammatory-and-regenerative-prop-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Renee Davis,1 Alex Taylor,1 Regan Nally,1 Kathleen F Benson,2 Paul Stamets,1 Gitte S Jensen2 1Fungi Perfecti, Olympia, WA 98507, USA; 2NIS Labs, Klamath Falls, OR 97601, USACorrespondence: Gitte S JensenNIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, USATel +1 541 884-0112Fax +1403 441-5236Email gitte@nislabs.comPurpose: 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, flow-cytometry, 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 ordinationDavis RTaylor ANally RBenson KFStamets PJensen GSDove Medical Pressarticlecd69cytokinesgrowth factorsanti-viral peptidesmedicinal mushroomsmyceliumimmune supportredundancy analysis (rda)multivariate ordinationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 13, Pp 117-131 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	cd69 cytokines growth factors anti-viral peptides medicinal mushrooms mycelium immune support redundancy analysis (rda) multivariate ordination Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	cd69 cytokines growth factors anti-viral peptides medicinal mushrooms mycelium immune support redundancy analysis (rda) multivariate ordination Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Davis R Taylor A Nally R Benson KF Stamets P Jensen GS Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend
description	Renee Davis,1 Alex Taylor,1 Regan Nally,1 Kathleen F Benson,2 Paul Stamets,1 Gitte S Jensen2 1Fungi Perfecti, Olympia, WA 98507, USA; 2NIS Labs, Klamath Falls, OR 97601, USACorrespondence: Gitte S JensenNIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, USATel +1 541 884-0112Fax +1403 441-5236Email gitte@nislabs.comPurpose: 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, flow-cytometry, 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
format	article
author	Davis R Taylor A Nally R Benson KF Stamets P Jensen GS
author_facet	Davis R Taylor A Nally R Benson KF Stamets P Jensen GS
author_sort	Davis R
title	Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend
title_short	Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend
title_full	Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend
title_fullStr	Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend
title_full_unstemmed	Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend
title_sort	differential immune activating, anti-inflammatory, and regenerative properties of the aqueous, ethanol, and solid fractions of a medicinal mushroom blend
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/3e981e79452440eaa828421a7c0635c8
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Differential Immune Activating, Anti-Inflammatory, and Regenerative Properties of the Aqueous, Ethanol, and Solid Fractions of a Medicinal Mushroom Blend

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