Reishi Mushroom (Ganoderma lucidum): Scientific Overview of Composition, Mechanisms of Action and Therapeutic Applications

November 25, 2025 Polyextract Team

Ganoderma lucidum, commonly known as Reishi in Japan or Lingzhi in China, represents a mushroom of major scientific interest that has been the subject of extensive investigations for several decades. This basidiomycete from the Ganodermataceae family has served as a cornerstone of Asian traditional medicine for over 2,400 years and currently attracts growing interest in modern biomedical research. This review examines (though not exhaustively) the bioactive compounds found in Reishi, their molecular mechanisms of action, and the therapeutic applications studied by modern scientific research.

Reishi Historical Context & Botanical Classification

Reishi grows naturally in subtropical and temperate regions of Asia, Europe, and America, primarily on dead or living wood of deciduous tree species in conditions of high humidity and limited light.

Historically, this mushroom was recognized by herbalist Shen Nong of the Shu dynasty and classified as a "superior herb", a designation reserved for substances that could be consumed continuously without side effects. Traditional Chinese medicine identifies six varieties of Reishi based on their coloration (red, black, blue, white, yellow, and violet), with red Reishi (Ganoderma lucidum) and black Reishi (Ganoderma sinensis) demonstrating the most significant therapeutic properties. [1]

Reishi Chemical Composition & Bioactive Molecules

General Structure and Nutritional Profile

Reishi displays a remarkably complex molecular profile. Fresh fruiting bodies contain up to 90% water. On a dry-weight basis, the mushroom is composed of: proteins (10-40%), lipids (2-8%), carbohydrates (3-28%), fiber (3-32%), and ash (8-10%).

More than 600 chemical compounds have been identified and isolated from Ganoderma lucidum, including alkaloids, meroterpenoids, nucleobases, nucleosides, polysaccharides, proteins, steroids and triterpenes. [3][2][4][1]

Triterpenes and Ganoderic Acids in Reishi Mushroom

Triterpenes constitute one of the two main classes of bioactive compounds in Reishi. More than 150 triterpenes have been identified in the fruiting bodies, spores and mycelium. [1]

Among them, ganoderic acids are highly oxygenated triterpenes with complex molecular structures. The most studied include ganoderic acids A, B, C1, C2, D, DM, E, F, G, H, K, Me, Mk, R, S, T, X and Y, as well as lucidic acids A, B, C and N.

For example:

Ganoderic acid A carries hydroxyl groups at positions 7 and 15.
Ganoderic acid H is hydroxylated at position C-3.

These subtle structural differences directly influence the molecules’ biological activity. [1][3][2][4][5]

Polysaccharides and Beta-Glucans in Reishi

Polysaccharides are the second major class of bioactive compounds in Reishi. More than 200 distinct polysaccharides have been isolated from fruiting bodies, spores, mycelium and liquid cultures. [1][2]

Structurally, these are mostly high-molecular-weight heteropolymers in which glucose is the main component, with variable proportions of xylose, mannose, galactose and fructose.

The main bioactive polysaccharides are (β = beta) β-1,3 and β-1,6-D-glucans. The cell walls of Reishi spores are particularly rich in these polysaccharides.

Chemically, beta-glucans are characterized by:

A main chain of glucose residues linked by β-1,3 glycosidic bonds
Branches attached via β-1,6 bonds

This three-dimensional configuration is key to their ability to interact with specific immune receptors. [6][7][8][9][10][11][1][2]

Several glycoproteins and polysaccharide–peptide complexes have also been described, including: [1][2][12]

GLIS (Ganoderma lucidum Immunomodulation Substance)
GLPG (Ganoderma lucidum proteoglycan)
GL-PP (Ganoderma lucidum polysaccharide–peptide)
Various glycoprotein fractions

Other Bioactive Compounds in Reishi

Reishi Mushroom also contains:

Phenolic compounds
Sterols (including ergosterol, a precursor of vitamin D₂)
Essential fatty acids (notably C19 polyunsaturated fatty acids)
Proteins rich in essential amino acids (especially leucine and lysine)
Nucleotides and nucleosides
Essential minerals

Mineral analyses have reported meaningful levels of:

Potassium: 3590 mg/100 g
Phosphorus: 4150 mg/100 g
Calcium: 832 mg/100 g
Magnesium: 1030 mg/100 g
Iron: 82.6 mg/100 g

as well as zinc, copper and selenium. [1][2][13]

Molecular Mechanisms of Action

Available data suggest several major axes of action, primarily described in in vitro models and animal studies.

Immunomodulatory Mechanisms of Reishi Polysaccharides

Reishi polysaccharides, particularly beta-glucans, have been studied for their capacity to modulate the immune system. Across multiple studies, they are associated with stimulation and modulation of host defenses. [7][9][10][11][12][6][1][2]

Beta-Glucans bind to specialized receptors on the surface of immune cells, including CR3, Dectin-1 and TLR-2. This interaction activates intracellular signaling pathways. Put simply, these signals “wake up” the immune system: certain cells proliferate, become more active, and increase the production of controlled pro-inflammatory messengers (cytokines). [7][12][6][14][9]

In this context, studies report:

Increased production of cytokines such as TNF-α, IFN-γ, IL-2 and IL-6
Enhanced natural killer (NK) cell activity, particularly in the spleen

In humans, a meta-analysis of controlled clinical trials found that intake of Reishi Extract was associated with increases in certain immune markers:

CD3+ T lymphocytes: +3.91% (95% CI: 1.92–5.90; p < 0.01)
CD4+ T cells: +3.05% (95% CI: 1.00–5.11; p < 0.01)
CD8+ T cells: +2.02% (95% CI: 0.21–3.84; p = 0.03)

Slight increases in NK-cell activity and total white blood cell count were also observed.[15][16]

These findings suggest measurable modulation of the immune system in exploratory clinical studies.

Cytotoxic and Antitumor Mechanisms of Reishi Triterpenes

In laboratory settings, several Reishi triterpenes, particularly ganoderic acids, have been studied for their direct effects on cancer cells. [1][2][5]

For example, ganoderic acid T can trigger apoptosis (a form of programmed cell death) in lung cancer cells through mitochondrial pathways. In an in vitro model, a concentration of 50 μg/mL resulted in approximately 70% reduction in cancer cell viability after 24 hours, without comparable effects on normal cells. This compound also reduces tumor colony formation and inhibits cell invasion and spread in certain models by notably decreasing the expression of enzymes involved in tissue degradation and cell migration (MMP-2 and MMP-9). [1][2][5]

Ganoderic acid X has been described as inhibiting enzymes linked to DNA structure (topoisomerases) and as triggering apoptosis via ERK and JNK pathways. Ganoderic acid Me has been associated with decreased proliferation and invasion of cancer cells through reduction of MMP-2/9, NF-κB, uPA, and iNOS. [1][2]

Other studies indicate that ganoderic acids A and H can slow the growth and invasive behavior of breast cancer cells by modulating AP-1 and NF-κB. Ganoderic acid Me has also been studied for its capacity to induce apoptosis of MDA-MB-231 breast cancer cells by decreasing the expression of several key actors: NF-κB, TNF-α, VEGF, IL-6/8, MMP-9, Bcl-2, c-Myc, and CCND1. [1][2][5]

These findings remain preclinical (cell and animal models) and do not directly translate into proven efficacy in humans, but they help clarify how certain Reishi compounds may act at the cellular level.

Antioxidant Properties of Reishi

Reishi extract is extensively studied for its antioxidant properties (its ability to help neutralize free radicals, unstable molecules that can damage cells). [1][2][13][18][19]

In several models, Reishi extracts increase the activity of two major antioxidant enzymes:

Superoxide dismutase (SOD)
Catalase

Both are involved in eliminating reactive oxygen species (ROS).

Triterpene-rich extracts often show the strongest in vitro antioxidant effects. Molecules such as various ganoderic acids, lucidic acid B and ganodermanontriol are frequently cited as major contributors to this activity.

Low-molecular-weight polysaccharides also demonstrate notable antioxidant effects. Their high density of hydroxyl groups enables them to donate electrons to free radicals and neutralize them.

Polysaccharide–protein complexes from Reishi (containing amino acids such as tyrosine, methionine, histidine, lysine and tryptophan) appear particularly effective at scavenging superoxide and hydroxyl radicals, thanks to these amino acids’ ability to donate protons.

In some tests, the antioxidant activity of a Reishi polysaccharide (GLP) was judged comparable to that of BHT. Other studies report mitochondrial protection, increased serum insulin and reduced lipid peroxidation under experimental conditions.

Reishi Anti-inflammatory Mechanisms

Bioactive compounds extracted from Reishi mushroom have also been studied for anti-inflammatory effects. In different models, triterpenes and polysaccharides are associated with reduced production of pro-inflammatory cytokines such as IL-1β, TNF-α and IL-6. [20][21][22][23][24]

Ganoderma lucidum spore oil (GLSO), for example, has been studied in stress-associated tumor models. It appears to reduce tumor progression by improving macrophage phagocytic capacity via Fcγ receptors (FcγR), linked to FcγR/SYK type signaling pathways.

The GLPP polysaccharide-peptide demonstrated, in cyclophosphamide-immunocompromised mice, improvements in:

Immune organ indices
Certain phagocytosis parameters
TNF-α, IFN-γ, IL-2 secretion
IgA levels

Metabolomic analyses indicate that GLPP might act on several central metabolic pathways: citric acid cycle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid pathway, and cAMP pathway.[12]

These data remain primarily experimental, but they support the potential of certain Reishi bioactives to modulate inflammation.

Therapeutic Applications and Studied Benefits of Reishi

Anti-Aging Properties of Reishi Mushroom

Reishi mushroom (Ganoderma lucidum) demonstrates anti-aging properties through multiple mechanisms.

Aging is a multifactorial process driven by oxidative stress, chronic inflammation, mitochondrial dysfunction and immune decline. [18][19][13]

Key bioactives from Reishi, including polysaccharides (especially β-D-glucans), triterpenoids (ganoderic acids), peptides, sterols and phenolic compounds, exert anti-aging effects via several pathways:

Polysaccharides enhance antioxidant defenses, reduce the accumulation of free radicals and modulate immune responses, potentially delaying immunosenescence.
Triterpenoids protect mitochondria, dampen pro-inflammatory signaling and prevent excessive apoptosis, contributing to neuroprotective and cardioprotective effects.
Peptides and sterols help limit oxidative DNA damage, support tissue repair and maintain membrane stability.
Phenolic compounds help regulate cellular redox pathways and may delay cellular senescence. [19]

Experimental studies in cell and animal models have shown that Reishi mushroom extracts can improve lifespan, cognitive function and stress resistance, supporting its classification as a natural geroprotective candidate.

Multiple isolated bioactive components from Reishi mycelial culture, including Ganodermasides A, B, C and D; Reishi 3 polysaccharide fraction; G. lucidum polysaccharides I–IV; G. lucidum peptides; polysaccharide–peptide complexes; total triterpenes; and ganoderic acid C1, have been associated with lifespan extension or related activities in model organisms. [13][19]

These observations place Reishi among the more promising candidates in natural aging research, although evidence in humans remains limited and requires confirmation.

Reishi and Cancer: Evidence for Use as an Adjuvant Supplement ?

The most extensively documented application of Reishi (Ganoderma lucidum) concerns adjuvant cancer treatment. A 2016 Cochrane systematic review analyzed five randomized controlled trials including 373 cancer patients (primarily Chinese population) and revealed that Reishi Extract administration combined with chemotherapy or radiotherapy increases the probability of positive tumor response compared to conventional therapy alone (RR 1.50; 95% CI: 0.90 to 2.51, P = 0.02). [20][21][22][24][25][26][16][15][5][1]

However:

Ganoderma lucidum alone did not show regression rates comparable to those observed with combined therapy.
Patients receiving Reishi supplementation had 1.27 times higher odds of responding to chemo- or radiotherapy than controls.

The review also noted improvements in quality of life (Karnofsky performance scale) in patients receiving Reishi supplements compared with controls (RR 2.51; 95% CI: 1.86–3.40; P < 0.01).[15][16]

A cross-sectional survey of cancer patients using Reishi found that most reported symptomatic improvements, although some also reported minor adverse effects (for example, mild nausea or insomnia). No significant hematologic or hepatic toxicity was reported in the clinical studies reviewed. [15][16][27]

Preclinical studies further indicate that ganoderic acids can inhibit proliferation in 26 different human cancer cell lines, with particularly strong antiproliferative activity in leukemias, lymphomas and myelomas. In acute promyelocytic leukemia cells, ganoderic acid induces mitochondrial damage leading to apoptosis, while sparing normal mononuclear cells. Active lipids extracted from Reishi spores can trigger apoptosis mediated by down-regulation of phosphorylated Akt (P-Akt) and up-regulation of caspases-3, -8 and -9.[5]

Taken together, these data suggest a potential role for Reishi as a natural complementary option in oncology, strictly under medical supervision, and do not justify replacing evidence-based cancer treatments.

Reishi: Neuroprotection and Neurodegenerative Diseases ?

Reishi triterpenes and polysaccharides are also being investigated for their neuroprotective potential. [19][24][18][13][1][2]

Key findings from experimental models include:

Aqueous and supercritical CO₂ extracts have shown partial inhibition of acetylcholinesterase (AChE), an enzyme targeted in the management of Alzheimer’s disease, with inhibition of up to ~22.5% in some tests.
In models of cerebral oxidative stress and neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s disease, ALS), Reishi’s antioxidant properties appear to reduce certain markers of neuronal damage. [24][1][2]
Isolated polysaccharides have demonstrated antidepressant-like effects and reduced anxiety-like behaviors in rats.

Traditionally, Reishi is also described as having relaxing and analgesic properties. [1] However, human studies in this area remain preliminary and do not yet support definitive clinical recommendations.

Reishi and Gut Microbiota Modulation

Recent work suggests that Reishi can influence gut microbiota, particularly through its polysaccharides, triterpenoids, oligosaccharides and trace elements.[44]

In models of hyperglycemia, hyperlipidemia and obesity associated with dysbiosis, certain Reishi extracts appear to improve both metabolic parameters and gut microbiota composition.

An LC/MS study in diabetic rats showed that Ganoderma lucidum can modify blood glucose and intestinal flora composition. Reishi mushroom polysaccharides are described as having prebiotic-like effects, supporting the growth of certain beneficial bacterial species. [45][42][44]

Again, these findings are primarily preclinical and point toward possible links between Reishi, gut microbiota and metabolism that require further clinical confirmation.

Antimicrobial and Antiviral Activities in Reishi Mushroom Extracts

Reishi extracts have been tested against various pathogenic bacteria. Aqueous and organic extracts (hexane, dichloromethane, ethyl acetate, methanol) have shown activity against:

Bacillus cereus
Enterobacter aerogenes
Staphylococcus aureus
Escherichia coli
Pseudomonas aeruginosa

In some assays, methanolic extracts were more active than ampicillin or streptomycin against S. aureus and B. cereus at defined concentrations. [1][2]

On the antiviral side:

Several isolated triterpenoids (ganoderic acid β, lucidumol B, ganodermanondiol, ganodermanontriol, ganolucidic acid A) have shown in vitro inhibition of HIV-1 protease, with IC₅₀ values between 20 and 90 μM.
Certain G. lucidum laccases can inhibit HIV-1 reverse transcriptase.
Water-soluble polysaccharides have demonstrated significant inhibition of plaque formation by herpes viruses HSV-1 and HSV-2. [1][2]

Molecular modeling studies further suggest that some ganoderic acids could interfere with HIV-1 attachment to the CD4 receptor. [46][1]

These results are exploratory and preclinical; they do not establish Reishi as an approved treatment for infectious diseases but highlight interesting biochemical interactions warranting further research.

Safety Profile and Tolerability of Reishi Mushroom

Overall, Reishi (Ganoderma lucidum) is a fungus that shows a favorable safety profile in clinical studies.

The Cochrane review mentioned above reports mainly minor adverse events, including mild nausea and insomnia in a subset of patients. No significant hematologic or hepatic toxicity was observed across the analyzed trials. [32][45][15][16][27]

In an oral repeated-dose toxicity study in Wistar rats, Mexican Reishi extracts showed no significant adverse, toxic or harmful effects in males or females compared with control groups. No kidney or liver lesions or dysfunctions were noted, and there were no abnormal changes in:

Organ weights
Tissue histopathology
Serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT, AST, total cholesterol, LDL-c, triglycerides, HDL-c)
Urinary parameters (creatinine, blood urea nitrogen, albumin, albumin/creatinine ratio, glucose)
Biomarkers of tissue injury and inflammation (protein expression of KIM-1/TIM-1, TLR4 and NF-κB; gene expression of IL-1β, TNF-α and IL-6)
Gene expression related to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr) [45]

In the previously mentioned cross-sectional survey of cancer patients who used Reishi as a supplement, most reported symptomatic improvement, although some experienced adverse events. [27] This underscores the importance of medical supervision, especially in fragile populations.

Limitations of Current Evidence and Future Research Directions

Despite a large body of preclinical work that is often described as promising, several limitations currently constrain the clinical use of Ganoderma lucidum:

Use of highly heterogeneous formulations (different mushroom parts, extraction methods and solvents, variable profiles of active compounds)
Study populations with diverse characteristics (disease type and stage, concurrent treatments, age, comorbidities)
Lack of standardized dosages and treatment durations
Follow-up periods that are often too short

Moreover, all trials included in the Cochrane review were conducted in Chinese populations, limiting the extrapolation of results to other regions and healthcare settings. [29][37][32][15][16]

Future research needs include:

More rigorous randomized controlled trials
Larger sample sizes and more diverse populations
Standardized preparations (with precise quantification of triterpenes, polysaccharides, etc.)
Longer follow-up with robust clinical endpoints, including survival

The identification and characterization of isolated (pure) Reishi compounds is also a key step. It would allow for a better understanding of specific mechanisms of action and, in the longer term, the design of better-characterized therapeutic formulations, while remaining grounded in evidence-based medicine.

Conclusion

Ganoderma lucidum (Reishi/Lingzhi) is a medicinal mushroom that ranks among the most studied and intriguing, alongside Lion’s Mane and Chaga. Its remarkable biological propertiesare closely tied to its complex chemical composition, dominated by triterpenes (notably ganoderic acids) and polysaccharides (particularly β-glucans).

Scientific research is actively exploring the immunomodulatory, antitumor, antioxidant, anti-inflammatory and neuroprotective mechanisms of its bioactive components. While preclinical data and early clinical studies are encouraging, especially regarding immune modulation and use as an adjuvant in oncology, current evidence does not support Reishi as a stand-alone treatment for cancer or other diseases.

At this stage, Reishi should be considered:

As a subject of ongoing biomedical research
As a potential food supplement option in certain contexts, always under medical supervision or in healthy populations
As a promising natural source of molecules for future, more targeted therapeutic developments

Scientific References on Reishi (Ganoderma lucidum)

Polyextract does not make any health claims or affirmations regarding the effects of Reishi or any other ingredient. This article is provided solely for educational and informational purposes. The scientific findings referenced here belong entirely to the authors of the cited publications and do not constitute medical advice or endorsement by Polyextract.com

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