Immunomodulatory Activities of a Fungal Protein Extracted from Hericium erinaceus through Regulating the Gut Microbiota

Abstract

A single-band protein (HEP3) was isolated from Hericium erinaceus using a chemical separation combined with pharmacodynamic evaluation methods. This protein exhibited immunomodulatory activity in lipopolysaccharide-activated RAW 264.7 macrophages by decreasing the overproduction of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and downregulating the expression of inducible nitric oxide synthase and nuclear factor-κB p65. Further researches revealed that HEP3 could improve the immune system via regulating the composition and metabolism of gut microbiota to activate the proliferation and differentiation of T cells, stimulate the intestinal antigen-presenting cells in high-dose cyclophosphamide-induced immunotoxicity in mice, and play a prebiotic role in the case of excessive antibiotics in inflammatory bowel disease model mice. Aided experiments also showed that HEP3 could be used as an antitumor immune inhibitor in tumor-burdened mice. The results of the present study suggested that fungal protein from H. erinaceus could be used as a drug or functional food ingredient for immunotherapy because of its immunomodulatory activities.

Natural Compounds in the Modulation of the Intestinal Microbiota: Implications in Human Physiology and Pathology

“…A single protein, called HEP3, isolated from H. erinaceus and administered to rats treated with trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis similar to IBD, was capable of restoring the microbiota diversity in treated rats. In particular, treatment with H. erinaceus single protein increased the amounts of Actinobacteria and Tenericutes, reduced those of Bacteroidetes and Firmicutes, and was able to restore a healthy-like ecological structure [128,129]. The effectiveness of HEP3 was also confirmed in other animal models of colitis [130].…”

Macrofungi: A review of cultivation strategies, bioactivity, and application of mushrooms

“…They induce T cell proliferation and differentiation by regulating gut microbiota composition and metabolism. Macrofungal proteins are nitrogen sources and growth factors that significantly promote the engraftment of bifidobacteria and other probiotics (Diling et al, 2017). Therefore, Macrofungal proteins may serve a prebiotic function in inflammatory bowel diseases (IBD) associated with excessive antibiotic administration.…”

Current Understanding of the Structure and Function of Fungal Immunomodulatory Proteins

“…These observations indicate that PCP might be a regulator of Th1/Th2 balance that favors the Th1 response. Anti-inflammatory and Anti-tumor Effects YZP and HEP3 could reduce activation of LPS-activated macrophages, suppress inflammatory cytokine expression, and show other anti-inflammatory and anti-tumor effects as well (27,31). YZP could modulate humoral immunity through regulating B-cell activation and suppressing macrophages via B cell in a mixed leukocyte reaction.…”

“…For instance, YZP was tested as a colonic inflammatory therapy on an acute colitis murine model, and the effects observed were primarily by B cell regulation (27). Comparably, HEP3 showed stronger potential as a colonic inflammatory treatment, and even in tumor therapy (31). It could suppress LPS-activated macrophages by reducing inflammatory cytokines and downregulating the expression of inducible NO synthase and NK-κB p65 in vitro.…”