Medicinal Mushrooms and Immunomodulation

Medicinal Mushrooms & Immunomodulation

The Professional Division, Mycolivia medicinal Mushrooms Ltd.

Autoimmune diseases are characterized by the cells of the immune system (antibodies and T lymphocytes) losing their immune tolerance and attacking cells and tissues of the body itself instead of attacking external invaders. Cancer occurs when the number of cells in the body divide uncontrollably and stop functioning according to their original purpose. Accumulation of such cells creates a malignant tumour (neoplasia), and in some cases, some of these cells migrate to other places in the body and form metastases.

The existence of homeostasis in the human body depends on the proper functioning of all body systems, which is made possible by coordination, regulation, and control between the various systems in the body, which operate in a mechanism of self-regulation (autoregulation), ie through the absorption of chemicals (hormones, antibodies, leukocytes, cytokines,) Or neural messages from other systems, and the use of a feedback mechanism (negative or positive) to correct themselves. Disorders or the inability of almost every aspect of this orchestrated response can produce serious consequences for body systems. The feedback mechanisms actually prevent sharp deviations from the normal values of the internal environmental indices of the body systems, thus preventing diseases.

Immunomodulation (Immunomodulation) is defined as inhibiting the progression of an immune response or an inflammatory condition, without causing significant immunosuppression. Immunomodulation is actually a change in the immune response or function of the immune system by activating substances that contribute to calming the activity of the immune system.

Immunomodulators are internal or external substances that regulate or alter the extent, type, duration, or ability of the immune response. Immunomodulation therapy basically interferes with the self-regulatory mechanism of the body’s defined systems, through drugs that affect the self-regulatory processes of the immune system.

What are the main mechanisms involved in immunomodulation?

In recent years attempts have been made to treat many diseases involving immune mediators by providing biological or chemical substances that activate or suppress major pathways in the immune system. The organism’s response to disorders in the regulatory pathways of the immune system can be called Biological Response Modification.

Biological Response Modifiers (BRMs – Biological Response Modifiers ) are substances that the human body naturally produces, or those produced in the laboratory, and stimulate the immune system’s response to infection or inflammation.

They are used to treat cancer and many autoimmune diseases, such as rheumatoid arthritis (RA), lupus, psoriasis, multiple sclerosis (MS), and more. BRMs include:

Anti-inflammatory drugs, such as NSAIDs and corticosteroids (which act by suppressing the secretion of cytokines and having an effect against lymphocyte-type immune cells)

Immunosuppressants, lower the activity of the body’s immune system. For example, Cyclosporine, which is used to prevent the rejection of transplanted organs, or Methotrexate, which treats rheumatoid arthritis (RA), psoriasis, and various types of cancer (Methotrexate inhibits the activity of the enzyme responsible for the breakdown of folic acid, The cell and its DNA structure. In the treatment of psoriasis, methotrexate limits the rapid cell division, which causes the accumulation of skin cells and the formation of thickened skin). Or Imuran and Purinethol, which interfere with the formation of building blocks for cell formation and inhibit the activation of T lymphocytes, and also reduce the production of antibodies and the number of immune cells

Monoclonal antibodies – aim to kill inflammatory molecules, such as cancer cells. Examples of monoclonal antibodies are the biological drugs Avastin or Erbitux, which are used to treat cancer. These drugs are “guided missiles” consisting of monoclonal antibodies unique to the cancerous tumor, which are chemically linked to toxins that cause cell apoptosis. Binding of the antibody to a specific cancer antigen uniquely brings the toxin closer to the target cell, the associated antibodies tend to move across the cell membrane, and at the end of the process the cell “swallows” the toxin-associated antibodies

Anti-interleukins – a group of cytokines that affect the immune system in a variety of mechanisms, such as encouraging the production of NK cells, encouraging the production of lymphocytes, encouraging the production of IgE antibodies, and more, thus improving the body’s response to pathogen penetration. In autoimmune diseases, these cytokines work harder, thus encouraging the immune system to attack the body’s own tissues.

The biologics inhibit the production of interleukins involved in encouraging the development of autoimmune diseases, such as:

Anti-IL-2 and anti-IL-6, are cytokines involved in many inflammatory diseases and cancer;
Anti-IL-12 and IL-23, are involved in the process of developing psoriasis;
Anti-IL-17 is involved in the process of developing autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS), and in the formation of cancer cells.

Interferons – Cytokine secreted proteins are suitable in response to the penetration of invasive factors such as viruses, bacteria, parasites, or in response to the cell becoming cancerous:

Interferon-α and interferon-β are produced by most cell types in the body as a result of stressful situations in which the cells are located, and are the important factors in the local immune response to viral infection by activating macrophages and NK cells. Interferon-α is also active against cancerous tumors

Interferon-γ is secreted only from helper T-cells and NK cells into the bloodstream, where it recruits and activates various cells in the immune system, especially Th1 cells, T-killers, antigen-presenting cells, and macrophages

This role makes it an important component in many inflammatory processes, including the body’s response to viruses, bacteria, parasites, and malignant cells. Cytokine overactivity can lead to autoimmune diseases.

Interferons are used to biologically treat a variety of autoimmune diseases, many cancers, and type C viral hepatitis.

TNF-α inhibitors – the cytokine Tumor Necrosis Factor-alpha is involved in the development of a variety of autoimmune diseases, such as rheumatoid arthritis (RA), psoriatic arthritis, Crohn’s disease, ankylosing spondylitis, asthma, and various cancers, such as leukemia.

How do medicinal mushrooms fit into the immunomodulation mechanism?

Medicinal mushrooms are attributed to biological roles belonging to the classification of BRM. The use of medicinal mushrooms can strengthen the immune response of the human body, thus increasing its resistance to disease, and in some cases even leading to a regression in the disease state.

In aerobic fermentation, the fungus produces substances called polysaccharides (polysaccharides). As long as the carbon source in the substrate does not constitute a limiting factor for the development of the fungus, it utilizes the excess monosaccharides to produce the polysaccharides. The higher the glucose concentration in the substrate ß the fungus will produce more polysaccharides.

Polysaccharides provide vital information to all branches of the immune system and allow the identification of pathogenic and cancerous tissues by the immune system as foreign cells to the body. As a result, accurate immune response is created against the pathogenic and cancerous cells, and the spread of the disease or the formation of metastases is prevented.

Immunologists have found that the receptors on the surface of innate immune cells called dectin-1 and a complementary protein receptor 3 (CR3 or CD11b / CD18) are responsible for the binding of β-glucans polysaccharides to them, allowing the immune system cells to recognize them.

β-glucans are absorbed into the bloodstream in two ways:

Passive intestinal absorption (penetration through spaces in the epithelial tissue).

A foreign pathogen penetrates the body or a cancer cell is formed
ß-glucans polysaccharides attach to M-cells on the spaces in the epithelial layer of the cell and penetrate with them into the cell
These ß-glycans provide information to the macrophages of the immune system in the cell to identify pathogens or cancerous cells
Then transfer them to the lymph system where they are neutralized.

Absorption through a protein receptor in the small intestine called TLR (Toll-Like Receptor), which is a protein receptor expressed in sentinel cells such as macrophages and dendritic cells, whose function is to detect pathogens that have invaded the intestinal mucosa or skin mucosa, and activate the immune response against the pathogen.

A foreign pathogen enters the body or a cancerous cell is formed ß Glucans polysaccharides bind to the TLR receptor on the cell, thus penetrating the target cell resulting in an immune response is created that causes the release of cytokines that produce CD4 + cells and Th0ß cells that activate these Th1 cells through interferons Of cytokines and NKß T cells and the latter attack the bacterium/virus/cancer cell.

The predominant medicinal mushrooms with an immune control mechanism to treat autoimmune diseases are:

GANODERMA LUCIDIUM (Reishi)

Main polysaccharides bind to the CR3 receptor on macrophages and reduce the release of cytokines and IL-6, IL-1β, TNF-α, and INF-γ

Gnodermic acid (found in the spores of the fungus) inhibits the release of histamine by mast cells (by inhibiting the entry of calcium ions into the mast cell)

Decreases RF (Rheumatoid Factor) levels that cause rheumatoid arthritis (RA).

Reduces the levels of the antibody Anti Phospholipid AB, which causes clotting problems in the arteries and veins, which occur due to the presence of autoantibodies against phospholipids (components in the cell membrane)

decreases tyrosinase levels, which are responsible for several actions in the melanin synthesis pathway.

Eliminate toxins and toxic metals from the body

Encourages the production of white blood cells in the immune system

Has antiviral and antibacterial activity against Helicobacter pylori

Has anti-intestinal parasite activity

Has the ability to boost apoptosis of lung cancer cells mediated by the mitochondria of these cells

Prevents the spread of cancer cells and encourages their apoptosis

Suppresses angiogenesis by inhibiting the secretion of substances that promote angiogenesis in cancer cells

CORDYCEPS SINENSIS – CORDYCEPS SINENSIS

Increases Th1 levels and reduces Th2 levels, which cause an allergic reaction in the lungs and kidneys

Has the anti-autoimmune activity on the kidneys in NEPHRITIS conditions

Inhibits TNFB1 production, which causes fibrosis of the liver (cirrhosis of the liver)

Encourages collagen production (responsible for tissue healing and healing) while inhibiting Metalloproteinase (TIMP) which impairs the intercellular matrix

Decreased levels of anti-ds-DNA antibodies in Lupus Nephritis conditions

Has the ability to prevent the spread of cancer cell growth

Cordyceps mycelium contains unique sterols with anti-carcinogenic activity

Encourages the production of NK cells (Natural Killers)

AGARICUS BLAZEI

Increases Th1 levels and reduces Th2 levels, which cause an allergic reaction in the lungs, intestines, and skin

Reduces pro-inflammatory cytokines in inflammatory bowel disease (IBD) – Crohn’s and ulcerative colitis

Reduces IgE antibody levels, which cause an allergic reaction.

Increases T lymphocyte cell levels in the thymus gland (these cells are formed in the bone marrow and reach the thymus gland to differentiate. These cells help the body fight infections)

Increases the activity of macrophages

Its polysaccharides have the ability to inhibit the continued growth of cancerous tumors

The most widely studied medicinal mushrooms with the function of immune control in cancer are:

TRAMES VERSICOLOR – CORIOLUS VERSICOLOR

Krestinin, the first prescribed medicine for the treatment of cancer was produced from the mushroom. Krestinin is based on the polysaccharides PSP and PSK. The drug was registered in Japan as earlier as 1977 for the treatment of breast cancer, lung cancer, and gastrointestinal cancer

The anticarcinogenic activity of β-glucan PSP on endothelial tumor markers (Factor VIII) causes a decrease in vascular density and the weight of the cancerous tumor, and a delay in the growth of endothelial cells.

PSP and PSK encourage the production of white T cells in the immune system

Increases the weight of the thymus gland

Increases the biological effects of radiation

Has toxic effects directly on cancerous cells and inhibits tumor growth

Increases the production of IL-2, IgG, C3, and interferon

Increases the activity of NK cells and macrophages

Maintains white blood cell counts and even raises them

Reduces the side effects of chemotherapy and radiation

Reduces pain in terminally ill patients

Prevents liver damage caused by CCl4 (carbon tetra-based drugs)

LENTINUS EDODES – SHIITAKE

The cancer drug Lentinan is produced from the polysaccharides of Shiitake mushroom for gastric and stomach cancer in Japan as earlier as 1985
Β-glucan in the shiitake mushroom is attributed to an activity that stimulates the immune system and activates specific cells and proteins that attack cancer cells, including macrophages, T cells, and NK cells
In laboratory studies, β-glucan demonstrated a slowdown in the growth of cancer cells in cell cultures
Lantinan encourages the production of white blood cells in the immune system
Lantinan has anti-cancer effects in colon cancer cells resulting from the ability to produce cytochrome P450 1A enzymes, which are known to have pro-carcinogenic substances in their active form
Lantinan has antifungal properties, inhibits the proliferation of leukemia cells, and suppresses the activity of reverse HIV-1
Shiitake has antiproliferative activity, immunostimulatory activity, hepatoprotective activity, anti-mutagenic activity in DNA (antimutagenic) genes, and anti-cancerous activity.

GRIFOLA FRONDOSA – MAITAKE

D-Fraction extracted from Maitake mushroom significantly suppresses the growth of cancerous tumors, in parallel with an increase in TNF-α and INF-γ levels produced in the spleen, and a significant increase in NK cells produced by TNF-α stimulation.

D-Fraction from Maitaka causes increased macrophage formation resulting from an increase in IL-12 levels, which is used to activate NK cells

D-Fraction promotes the production of IL-1, which promotes the activation of T cells

D-Fraction encourages the production of Super Oxide Anion, which directly harms cancer cells.

The main mechanisms of action of the polysaccharides in medicinal mushrooms used as BRMs are :

Invokes an anti-inflammatory response

Prebiotic influence

Decreases an anti-parasitic reaction

Decreases of 2Th levels that trigger an allergic reaction

Reduces Super Oxide Anion levels, which directly affect cancer cells

Elevation of phagocyte activity

Invokes modulation of macrophages

Reduction of eosinophil irritation

Increases antioxidant levels of:

– GPO (Glutathione Peroxidase)
– SOD (Sodium Oxide Dismutase)
– CATALASE

Inhibition of the release of histamines from mast cells, induce an allergic reaction.

Benefits of using BRMs extracted from medicinal mushrooms, which distinguish them from the biological drugs used against cancers and autoimmune diseases:

– Do not cause additional damage or stress to the body
– Have an adaptogenic activity that allows the body to cope with environmental stress and biological stress
– Have activities that support more than one system (vaccine, nerves, hormonal, etc.)
– Does not cause side effects that often occur with treatment of drug-induced BRMs, such as flu-like symptoms (chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhea), rash, bleeding, swelling.