Ganoderma, a genus that includes approximately 80 species, is most commonly associated with Ganoderma lucidum. Ganoderma species such as Ganoderma lucidum are known for their rich composition of biologically active compounds in their fruiting bodies, mycelium, and spores. These compounds include around 400 different biologically active compounds, mainly triterpenes, polysaccharides, nucleotides, sterols, steroids, fatty acids, proteins, peptides, and trace elements. Over the past 2,000 years, Ganoderma species have been widely used in Asian countries, such as China, Japan, and Korea, as a “mushroom of longevity and immortality” and traditionally employed for various therapeutic purposes.
What Are the Main Health Benefits of Ganoderma?
The most health-beneficial compounds found in Ganoderma are polysaccharides with immune-stimulating properties and triterpenoids with cytotoxic effects. These compounds are recognized for their abilities to regulate the immune system, act against viruses, bacteria, and oxidation, protect the liver, and potentially exert anti-cancer properties. Numerous clinical studies have confirmed the anti-tumor potential and anti-tumor cell migration effect of compounds extracted from Ganoderma. Therefore, Ganoderma supplements are increasingly embraced by the public, with the aim of enhancing immune function and supporting cancer prevention.
How Does Ganoderma Enhance Immunity?
Ganoderma’s immune-regulating effects are broad, encompassing the enhancement of innate immunity, humoral immunity, and cellular immunity. In particular, Ganoderma polysaccharides can help boost the immune system and regulate immune-related cells, including B cells, T cells, dendritic cells, macrophages, and natural killer cells. These compounds facilitate immune organ growth, the release of cytokines, and other immune-regulating functions .
Ganoderma polysaccharides enhance the immune system by increasing and regulating various immune cells in the body. Understanding how polysaccharides interact with various immune effector cells in the body can serve as an adjunctive therapy for various immune diseases and tumor treatments.
Dendritic cells are one of the most potent antigen-presenting cells in the body and play a crucial role in initiating primary immune responses. Mature dendritic cells can effectively activate initial T cells, thereby enhancing immune competence. Research results indicate that Ganoderma polysaccharides promote the maturation and functional regulation of dendritic cells in murine bone marrow cultures, helping to initiate dendritic cell-induced immune responses.
Macrophages are major antigen-presenting cells, primarily involved in inducing and regulating specific immune responses. Animal studies have shown that Ganoderma polysaccharide extracts significantly increase the phagocytic capacity of macrophages, surpassing that of control groups. It has also been suggested that Ganoderma polysaccharides act by stimulating macrophages to release TNF-α, which in turn modulates immune function.
Particularly, cytotoxic T cells (T killer cells) and helper T cells (T helper cells) are essential components of cellular immunity in the body. Cytotoxic T cells can directly attack foreign antigens, while helper T cells can indirectly kill foreign cells by releasing cytokines. Research indicates that Ganoderma polysaccharides promote DNA synthesis in T cells. Cell culture experiments also show that Ganoderma polysaccharides directly stimulate T cell proliferation11], enhancing immune regulation by promoting T cell synthesis and proliferation.
B cells play a crucial role in humoral immune responses, primarily producing antibodies (immunoglobulins such as IgM and IgG) to combat foreign antigens. Animal studies suggest that Ganoderma polysaccharides activate B cells and macrophages. Furthermore, research has found that Ganoderma polysaccharides can enhance antibody (IgM) production, thus improving humoral immunity. Studies have also indicated that β-(1→3) main chain and β-(1→6) side chain glucan polysaccharides can promote the secretion of antibodies (e.g., IgA and IgG) in the body, thereby modulating immune responses.
Natural Killer Cells
Natural killer cells are considered part of the body’s innate defense system. They also serve as important mediators, particularly in some antibody-dependent cytotoxicity. Natural killer cells have cytotoxic activity against specific cells, and their function is associated with hypersensitivity reactions and autoimmune diseases. Cell experiments indicate that the addition of Ganoderma polysaccharide extracts increases the quantities of macrophages, dendritic cells, and natural killer cells by 1.5 times more than control groups. In certain proportions, natural killer cell-induced cytotoxicity increases significantly by 31.7%.
This text explains the health benefits of Ganoderma, its immune-enhancing mechanisms, and how it affects different immune cells in the body. Ganoderma is known for its potential to regulate and boost the immune system through its active compounds, particularly polysaccharides and triterpenoids.
Mechanisms of Ganoderma’s Anticancer Effects
The anticancer effects of Ganoderma and its extracts have been extensively proven, including inhibiting cancer cell proliferation and inducing apoptosis, as well as combating metastasis, angiogenesis, and more. Ganoderma polysaccharides don’t directly attack cancer cells; instead, they indirectly produce antitumor effects by activating different immune responses in the body.
Research indicates that the synthesis of nitric oxide by macrophages requires the structure of β-(1→3) glucan. The most active immunoregulatory polysaccharide is β-(1→3)-glucan, which is the richest in Ganoderma polysaccharides. Studies reveal that β-(1→3)-glucan-containing polysaccharides in Ganoderma possess antitumor and immunoregulatory effects. Ganoderma activates the body’s ability to combat cancer cells through its immunomodulatory effect on immune cells. Research has also demonstrated that Ganoderma polysaccharides can enhance the cytotoxicity of natural killer cells against cancer cells.
Moreover, several studies directly point out that Ganoderma polysaccharides can inhibit cancer genes, exhibiting their ability to fight tumors. Results suggest that polysaccharides significantly inhibit the proliferation of human colorectal cancer cells and simultaneously suppress DNA synthesis in cancer cells, reducing the formation of free radicals.
Mutations or inactivation of the tumor-suppressing protein p53 gene is the most common genetic change in human tumors. In vitro studies reveal that Ganoderma polysaccharides exhibit the ability to inhibit cancer cell growth in human cells with normal p53 gene function, including various cancer cells such as colorectal, liver, lung, bone, leukemia, gastric, and breast cancer cells.
Ganoderma polysaccharides are also shown to induce intrinsic and extrinsic apoptosis in tumor cells, inhibiting cancer cell proliferation through the mediation of DNA transcriptional regulation.
- Promoting Intrinsic Apoptosis in Cells
Research indicates that polysaccharides can inhibit cancer cell viability while inducing cell apoptosis. The mechanism involves the disruption of DNA synthesis enzymes and the inhibition of pro-caspase-3, pro-caspase-6, and pro-caspase-9 protein expression, which may prevent tumor cells from replicating and transferring, ultimately exhibiting antitumor effects.
- Promoting Extrinsic Apoptosis in Cells
In vitro studies show that using human peripheral blood mononuclear cells and stimulating them with Ganoderma polysaccharides induces the production of innate inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-12, and interferon-gamma. The presence of TNF-α in particular leads to the external apoptosis of tumor cells, and other studies point out that Ganoderma polysaccharides stimulate macrophages to release TNF-α.
Active Ingredients in Ganoderma Polysaccharides
Ganoderma polysaccharides belong to fungal polysaccharides, a class of compounds composed of more than a dozen monosaccharides. To date, around 220 polysaccharides have been isolated from Ganoderma, primarily composed of β-glucans, with only a small amount of α-glucans. Typically, α-glucans are nearly biologically inactive, whereas β-glucans are considered the source of active ingredients.
Most Ganoderma polysaccharides are heterogeneous polysaccharides with linear or branched molecules, containing side chains made of glucose, galactose, mannose, fucose, xylose, or arabinose, connected through β-(1→3), β-(1→4), or β-(1→6) linkages; these polysaccharides exhibit different immunomodulatory effects when their structure or molecular weight changes. Among these, β-glucans are among the most widely reported bioactive polysaccharides and are generally considered reactive biological agents.
Particularly, polysaccharides made up of β-(1→3)-D-glucan with a high molecular weight and side branches of (1→6)-β-D-glucose have been recognized as the most biologically active structures in polysaccharides  .
β-(1→3) and β-(1→6) Side-Chain Glucans in Ganoderma Polysaccharides
Studies indicate that feeding mice with β-(1→3) main chain and β-(1→6) side-chain glucans extracted from Ganoderma can induce the expression of IgA or IgG, enhance the expression of immunoreceptors in the small intestine, regulate the activity of natural killer cells, and improve inflammatory conditions. Other studies find that β-(1→3) main chain and β-(1→6) side-chain glucans not only stimulate macrophage growth but also promote the release of tumor necrosis factor-alpha, leading to more comprehensive immunomodulatory effects.
Additionally, a review study analyzed 37 studies related to naturally occurring β-(1→3) main chain and β-(1→6) side-chain glucans. These studies involved daily supplementation of 2.5 to 1000 milligrams, with experimental periods of up to 6.5 months. The overall analysis found that (1) it enhances immune defenses, reducing the incidence and symptoms of colds, flu, and other respiratory infections, and (2) improves allergy symptoms. Hence, it is inferred that structures containing β-(1→3) main chain and β-(1→6) side chain exhibit the desired bioactivity for the intake of Ganoderma polysaccharides.
We can understand that Ganoderma polysaccharides can enhance the immune system and immune cells by regulating the immune system, leading to immunomodulation and antitumor effects. Numerous domestic and international studies particularly highlight the importance of β-(1→3) main chain and β-(1→6) side-chain glucans for enhanced biological activity. Depending on our health needs, we can consider whether Ganoderma supplementation is necessary, and when selecting related health products, it’s advisable to choose polysaccharides composed of β-(1→3) main chain and β-(1→6) side-chain glucans for the best effects.