Chronic low-grade inflammation is implicated in a range of conditions, from metabolic disorders to neurodegenerative diseases. Interest in botanical and fungal compounds that may help modulate inflammatory pathways has grown alongside this research. Several well-studied functional mushrooms have been investigated for their effects on inflammatory markers, and while preclinical evidence is more extensive than clinical data, the mechanistic picture emerging is instructive.
This article reviews what current research indicates about five functional mushrooms and their relationship to inflammation: Reishi (Ganoderma lucidum), Chaga (Inonotus obliquus), Turkey Tail (Trametes versicolor), Cordyceps, and Lion’s Mane (Hericium erinaceus).
How Functional Mushrooms May Interact With Inflammatory Pathways
Inflammatory responses are regulated by a network of cytokines, signaling cascades, and immune cells. Key mediators include tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and nuclear factor kappa B (NF-kB), a transcription factor that plays a central role in activating pro-inflammatory gene expression. Many functional mushrooms contain bioactive compounds, including beta-glucans, triterpenoids, and polysaccharides, that research suggests may interact with these pathways.
It is worth noting at the outset that most studies in this area are preclinical, conducted in cell cultures or animal models. Clinical trials in humans remain limited, and results have been mixed. The evidence is promising but does not yet support definitive conclusions about therapeutic efficacy in people.
Reishi (Ganoderma lucidum): Triterpenoids and Immunomodulation
Reishi is among the most extensively studied medicinal mushrooms. Its bioactive profile includes polysaccharides and a diverse array of lanostane-type triterpenoids. A 2026 comprehensive review of G. lucidum summarized evidence that these compounds exhibit immunomodulatory and anti-inflammatory properties through multiple mechanisms, including modulation of cytokine production and regulation of oxidative stress pathways.[1]
Preclinical studies have examined ganoderic acids, a class of triterpenoids in Reishi, in models of chronic inflammation. Research suggests these compounds may inhibit NF-kB activation and reduce production of pro-inflammatory cytokines such as IL-6 and TNF-a. However, clinical evidence for anti-inflammatory effects in humans remains limited, and a randomized controlled trial examining Reishi polysaccharide peptide in patients with cardiometabolic syndrome found no statistically significant changes in inflammatory biomarkers compared with placebo, highlighting the need for further well-designed human studies.
Chaga (Inonotus obliquus): Melanin, Polyphenols, and Gut Inflammation
Chaga is a parasitic fungus that grows primarily on birch trees and has a long history of use in northern European and Russian folk medicine. It is rich in melanin pigments, betulinic acid, and polyphenolic compounds with notable antioxidant properties.
A 2026 study published in Nutrients examined Chaga crude melanin (IOM) in a mouse model of dextran sulfate sodium-induced colitis. The researchers found that IOM administration significantly reduced colonic inflammation and oxidative stress markers, strengthened the intestinal barrier, and modulated gut microbiota composition. The study also identified suppression of neutrophil pro-NETotic signaling as a potential mechanism.[2]
These findings suggest that Chaga compounds may support mucosal inflammation resolution, particularly in the gut. As with other mushrooms in this overview, human clinical data are lacking and animal findings should not be directly extrapolated to human outcomes.
Turkey Tail (Trametes versicolor): PSK, PSP, and Cytokine Regulation
Turkey Tail is best known for polysaccharide-K (PSK) and polysaccharide-peptide (PSP), compounds that have been researched primarily in the context of immune support and adjunct cancer therapy in Japan and China. Research also suggests anti-inflammatory activity through distinct mechanisms.
A study published in the International Journal of Molecular Sciences investigated an extract of Coriolus versicolor (Turkey Tail) in a pro-inflammatory microenvironment model. The extract inhibited production of IL-6, IL-8, and metalloproteinase-9 (MMP-9) in lipopolysaccharide-stimulated cells, and was associated with reduced expression of Toll-like receptor 4 and phosphorylated IkB, a marker of NF-kB pathway activity.[3] These mechanisms are relevant to chronic inflammatory conditions, though the study was conducted in cell lines rather than human subjects.
Cordyceps: Cordycepin and NF-kB Pathway Modulation
Cordyceps fungi produce cordycepin (3-deoxyadenosine), a bioactive nucleoside that has been extensively studied for its anti-inflammatory properties. A 2026 review in the American Journal of Chinese Medicine summarized the molecular mechanisms by which cordycepin modulates inflammation, finding that it acts on multiple converging pathways: NF-kB, mitogen-activated protein kinase (MAPK), PI3K/Akt/mTOR, and the NLRP3 inflammasome.[4]
The review noted that cordycepin inhibits production of pro-inflammatory mediators including TNF-a, IL-1 beta, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), while promoting anti-inflammatory cytokines such as IL-10 and TGF-beta. It also appears to influence macrophage polarization toward an M2 (anti-inflammatory) phenotype. These findings are based largely on cell and animal models; human trials examining cordycepin specifically for inflammation are limited.
Lion’s Mane (Hericium erinaceus): Beta-Glucans and Mucosal Immunity
Lion’s Mane is most commonly discussed in the context of neurological health due to its hericenone and erinacine content, which may stimulate nerve growth factor (NGF). However, its beta-glucan fraction has also attracted research attention for anti-inflammatory and gut-protective effects.
A 2026 study published in the International Journal of Biological Macromolecules evaluated a beta-glucan-rich hot-water extract of Lion’s Mane in both cell models and a mouse colitis model. In macrophage cell cultures, the extract suppressed LPS-induced nitric oxide and pro-inflammatory cytokines (IL-6, MCP-1). In mice with DSS-induced colitis, oral administration improved disease activity and reduced serum cytokine levels, with histology confirming reduced mucosal damage. The extract also modulated gut microbiota composition in a manner associated with reduced inflammation.[5]
Shared Mechanisms and Research Gaps
Across these five species, several common themes emerge. Beta-glucans, polysaccharides, and species-specific secondary metabolites (triterpenoids in Reishi, cordycepin in Cordyceps, melanin in Chaga) appear to interact with overlapping but distinct aspects of inflammatory signaling. NF-kB inhibition and cytokine modulation appear frequently across the research literature.
However, important caveats apply. The majority of this research is preclinical. Bioavailability varies substantially between extract forms and delivery methods, and effective concentrations in animal models may not translate to achievable levels in humans. Additionally, the diversity of extraction methods, dosing protocols, and species variations between studies makes direct comparisons difficult. For an overview of how specific mushroom compounds are measured and standardized, see our guide to Reishi for immune support and what the clinical evidence shows.
Practical Considerations
Individuals considering functional mushroom supplementation for inflammatory concerns should be aware that no mushroom supplement is approved to treat or prevent any inflammatory condition. The research reviewed here indicates biological plausibility, not clinical proof.
Those with autoimmune conditions, individuals taking immunosuppressant medications, or those on anticoagulants should consult a healthcare provider before adding any mushroom supplement, as interactions are possible. Quality and standardization of commercially available products vary widely, and certificate of analysis verification is recommended before purchasing any supplement.
Summary
Functional mushrooms, including Reishi, Chaga, Turkey Tail, Cordyceps, and Lion’s Mane, contain bioactive compounds that research suggests may interact with inflammatory signaling pathways. Studies indicate effects on cytokine production, NF-kB activity, and immune cell behavior in preclinical models. Human clinical evidence remains limited, and the field would benefit from well-designed, adequately powered randomized controlled trials. The mechanistic data available support continued investigation of these fungi as potential adjunctive approaches to inflammation management, but should not be interpreted as evidence of therapeutic efficacy in the absence of robust human trial data.
References
- 1. Mohamed G, et al. Unlocking the Therapeutic Potential of Ganoderma lucidum: From Bioactive Compounds to Clinical Translation. Phytother Res. 2026. PMID: 42116536
- 2. Yuan H, et al. Inonotus obliquus Crude Melanin Ameliorates DSS-Induced Colitis with Modulation of Gut Microbiota and Neutrophil pro-NETotic Activation. Nutrients. 2026;18(11):1733. PMID: 42280375
- 3. Jedrzejewski T, et al. Extract from the Coriolus versicolor Fungus as an Anti-Inflammatory Agent with Cytotoxic Properties against Endothelial Cells and Breast Cancer Cells. Int J Mol Sci. 2020;21(23):9063. PMID: 33260615
- 4. Zhao Y, et al. Research Progress on the Molecular Mechanisms of Cordycepin in Modulating Inflammation. Am J Chin Med. 2026;54(3):859-880. PMID: 42057256
- 5. Yu H, et al. Beta-Glucan-rich Hericium erinaceus hot-water extract ameliorates acute colitis by suppressing inflammation, preserving the epithelial barrier, and modulating gut microbiota ecosystem. Int J Biol Macromol. 2026;354:151368. PMID: 41819322
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Functional mushroom supplements are not intended to diagnose, treat, cure, or prevent any disease. Consult a qualified healthcare provider before starting any new supplement.
