Agaricus blazei (Himematsutake)

Agaricus blazei Murrill, commonly called Himematsutake or “Brazilian mushroom,” is an edible basidiomycete native to Brazil but cultivated worldwide for its medicinal properties. The fruiting body and mycelial extracts are marketed as dietary supplements intended to modulate immune function and support overall health.

• Immune modulation: Clinical trials have shown that polysaccharide‑rich extracts increase NK‑cell activity and raise serum levels of IL‑2, IFN‑γ, and IL‑12, suggesting enhanced innate immunity (Kawaguchi et al., 2018).
• Antioxidant activity: β‑glucans and phenolic compounds from A. blazei reduce oxidative biomarkers (MDA, 8‑OHdG) in both animal models and small human studies, supporting cellular protection.
• Metabolic support: In randomized trials, daily 1–3 g of dried mushroom lowered fasting glucose and HbA1c by ~0.5 % in type‑2 diabetic patients, likely via improved insulin sensitivity.
• Anti‑inflammatory: In vitro and mouse studies demonstrate inhibition of NF‑κB and COX‑2, translating into reduced C‑reactive protein in pilot human trials.
• Potential anticancer activity: In vitro cytotoxicity against breast, colon, and leukemia cell lines is documented, and adjunctive use in cancer patients has shown modest improvements in quality‑of‑life scores, though robust clinical endpoints are pending.
• Potential neuro‑protective effects: Animal studies report preservation of hippocampal neurons and improved performance on maze tests, suggesting possible cognitive support.

The primary bioactive constituents are β‑glucans (β‑1,3/1,6‑glucans), polysaccharide‑protein complexes, and phenolic antioxidants. β‑Glucans bind dectin‑1 and complement receptor 3 (CR3) on macrophages, dendritic cells, and NK cells, triggering the Syk‑CARD9‑NF‑κB pathway, which up‑regulates cytokine production (IL‑2, IFN‑γ) and enhances phagocytosis. Simultaneously, β‑glucans stimulate the mTOR‑dependent “trained immunity” program, epigenetically reprogramming monocytes for heightened responsiveness. Phenolic compounds (e.g., gallic acid) scavenge reactive oxygen species and inhibit the NF‑κB cascade, lowering pro‑inflammatory cytokines (TNF‑α, IL‑6). In metabolic tissue, β‑glucans activate AMPK and improve GLUT4 translocation, increasing glucose uptake. Together, these pathways produce the observed immuno‑stimulatory, antioxidant, and metabolic effects.

The principal bioactive is a β‑1,3/1,6‑glucan polymer (C₆₆H₁₁₀O₅₆, MW ≈ 10–15 kDa). Its repeating unit is (β‑D‑glucose)ₙ linked by β‑1,3 backbone with β‑1,6 side‑chains. Phenolic constituents include gallic acid (C₇H₆O₅) and catechin (C₁₅H₁₄O₆) with typical flavonoid structures (C‑6′‑hydroxyl, C‑3′‑O‑glucoside). The mushroom also contains ergosterol (C₂₈H₄₄O) and small amounts of vitamin D₂. The polysaccharide is water‑soluble, forms viscous gels at 1–3 % w/v, and is resistant to gastric acid but hydrolyzed by intestinal β‑glucanases, allowing systemic immune activation via gut‑associated lymphoid tissue (GALT).

Commercial A. blazei is cultivated in Brazil, Japan, and China using controlled substrate (sawdust‑based) and sterile fermentation for mycelial extracts. The most consistent products are mycelial‑culture powders produced by submerged fermentation, which yields higher β‑glucan content (30–40 % w/w) than fruiting‑body powders. Quality indicators include: (i) ≥30 % β‑glucan (measured by enzymatic assay), (ii) absence of heavy metals (<5 ppm Pb, As, Cd), (iii) microbial limits (<10⁴ CFU/g total aerobic count). Standardization to a specific β‑glucan content is essential; third‑party certifications (e.g., GMP, ISO 22000) provide assurance. Wild‑harvested fruiting bodies are rare and may contain variable polysaccharide levels and higher contaminant risk, thus are less recommended for supplements.