Immunomodulatory properties of medicinal mushrooms: differential effects of water and ethanol extracts on NK cell-mediated cytotoxicity

Innate Immun. 2016 Oct;22(7):522-33. doi: 10.1177/1753425916661402. Epub 2016 Jul 28.

Abstract

Medicinal mushrooms have been used for centuries in Asian countries owing to their beneficial effects on health and longevity. Previous studies have reported that a single medicinal mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on conditions, but the factors responsible for this apparent dichotomy remain obscure. We show here that water and ethanol extracts of cultured mycelium from various species (Agaricus blazei Murrill, Antrodia cinnamomea, Ganoderma lucidum and Hirsutella sinensis) produce opposite effects on NK cells. Water extracts enhance NK cell cytotoxic activity against cancer cells, whereas ethanol extracts inhibit cytotoxicity. Water extracts stimulate the expression and production of cytolytic proteins (perforin and granulysin) and NKG2D/NCR cell surface receptors, and activate intracellular signaling kinases (ERK, JNK and p38). In contrast, ethanol extracts inhibit expression of cytolytic and cell surface receptors. Our results suggest that the mode of extraction of medicinal mushrooms may determine the nature of the immunomodulatory effects produced on immune cells, presumably owing to the differential solubility of stimulatory and inhibitory mediators. These findings have important implications for the preparation of medicinal mushrooms to prevent and treat human diseases.

Keywords: Agaricus blazei Murrill; Antrodia cinnamomea; Ganoderma lucidum; Hirsutella sinensis; Ophiocordyceps sinensis; caterpillar fungus; extraction; immunomodulatory effects; innate immunity; medicinal mushrooms.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / immunology*
  • Animals
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / drug effects*
  • Ethanol / chemistry
  • Humans
  • Immunomodulation
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Medicine, East Asian Traditional*
  • Mycelium
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Perforin / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Signal Transduction
  • Water / chemistry
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Plant Extracts
  • Water
  • Perforin
  • Ethanol
  • p38 Mitogen-Activated Protein Kinases