Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms’ anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions—tumor, inflammation and allergy—seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.

Medicinal mushrooms have documented effects against different diseases, including infections and inflammatory disorders. The related Basidiomycota Agaricus blazei Murill (AbM), Hericium erinaceus (HE), and Grifola frondosa (GF) have been shown to exert antimicrobial activity against viral agents, Gram‐positive and Gram‐negative bacteria, and parasites in vitro and in vivo. Since the mechanism is immunomodulatory and not antibiotical, the mushrooms should be active against multi‐drug resistant microbes as well. Moreover, since these Basidiomycota also have anti‐inflammatory properties, they may be suited for treatment of the severe lung inflammation that often follows COVID‐19 infection. An AbM‐based mushroom extract (Andosan™), also containing HE and GF, has been shown to significantly reduce bacteraemia and increase survival in mice with pneumococcal sepsis, and to improve symptoms and quality of life in IBD patients via an anti‐inflammatory effect. Hence, such mushroom extracts could have prophylactic or therapeutic effect against the pneumonic superinfection and severe lung inflammation that often complicates COVID‐19 infection. Here, we review antimicrobial and anti‐inflammatory properties of AbM, HE and GF mushrooms, which could be used for the battle against COVID‐19.

Two novel enzyme‐linked immunosorbent assays (ELISAs), designed to detect complexes containing DNA, leucocyte calprotectin and S100A12 proteins, were generated for improved specificity and rapid measurement of neutrophil extracellular traps (NETs). The assays were applied on plasma and serum samples from blood donors for establishment of reference values, and from patients with multiple myeloma (MM) or rheumatoid arthritis (RA) in order to examine putatively increased values in the two different inflammatory conditions. Although NETs were hardly detectable in healthy individuals, NET levels were as expected highly and statistically significantly increased in RA patients. The detection of statistically significantly increased NET levels in MM is a novel finding.

The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional medicine against cancer and other diseases. The mushroom contains immunomodulating β-glucans and is shown to have antitumor effects in murine cancer models. Andosan^™ is a water extract based on AbM (82%), but it also contains the medicinal Basidiomycetes mushrooms Hericeum erinaceus and Grifola frondosa. Tap water with 10% Andosan^™ was provided as the only drinking water for 15 or 22 weeks to A/J Min/+ mice and A/J wild-type mice (one single-nucleotide polymorphism (SNP) difference), which then were exsanguinated and their intestines preserved in formaldehyde and the serum frozen. The intestines were examined blindly by microscopy and also stained for the tumor-associated protease, legumain. Serum cytokines (pro- and anti-inflammatory, Th1-, Th2 -and Th17 type) were measured by Luminex multiplex analysis. Andosan^™ treated A/J Min/+ mice had a significantly lower number of adenocarcinomas in the intestines, as well as a 60% significantly reduced intestinal tumor load (number of tumors x size) compared to control. There was also reduced legumain expression in intestines from Andosan^™ treated animals. Moreover, Andosan^™ had a significant cytotoxic effect correlating with apoptosis on the human cancer colon cell line, Caco-2, in vitro. When examining serum from both A/J Min/+ and wild type mice, there was a significant increase in anti-tumor Th1 type and pro-inflammatory cytokines in the Andosan^™ treated mice. The results from this mouse model for colorectal cancer shows significant protection of orally administered Andosan^™ against development of intestinal cancer. This is supported by the finding of less legumain in intestines of Andosan^™ treated mice and increased systemic Th1 cytokine response. The mechanism is probably both immuno-modulatory and growth inhibition of tumor cells by induction of apoptosis.