​Lentinula Edodes (Shiitake Mushroom)

Lentinula Edodes (Shiitake Mushroom)

Product Name: Лентинула съедобная, Lentinula edodes, Shiitake, Seta shiitake, Lentin du chêne, فطر شيتاكي, เห็ดหอม, Shiitake qo‘ziqorini, Shiitake кози ё гриб, Şiitake göbələyi, Шитаки занбуруғ, Valgomieji šiitake, Šiitake sēne, Шіїтаке, Şiitake, שיטאקה

Synonyms: Шиитаке, японский лесной гриб, китайский чёрный гриб, shiitake mushroom, oakwood mushroom, forest mushroom, Schwarzer Chinapilz, japanischer Waldpilz, seta de roble, hongo shiitake, champignon noir chinois, lentin comestible, فطر البلوط, เห็ดหอมญี่ปุ่น, เห็ดชิตาเกะ

Parts Used: fruit body, mycelium, extract, spores, powder, extract, extracellular polysaccharides.

Main Indications for Use of Lentinula edodes: Prostate cancer, breast cancer, stomach cancer, colon cancer, benign prostatic hyperplasia, hypercholesterolemia, arterial hypertension, immunodeficiency states, viral hepatitis, chronic hepatitis B, chronic hepatitis C, herpesvirus infections, tuberculosis, chronic recurrent respiratory infections, atherosclerosis, neurodegenerative diseases, chronic fatigue syndrome.

Use of Lentinula edodes in mixtures and complexes: Osteoarthritis, rheumatoid arthritis, allergic rhinitis, bronchial asthma, atopic dermatitis, autoimmune thyroiditis, diabetic neuropathy, metabolic syndrome, irritable bowel syndrome, ulcerative colitis, Crohn's disease, liver cirrhosis.

Pharmacological Properties of Lentinula edodes: antioxidant, antitumor, immunomodulatory, hypolipidemic, anti-inflammatory, hepatoprotective, antiviral, antibacterial, antihypertensive, antiplatelet, antimutagenic, neuroprotective, prebiotic, antimycotic, adaptogenic, radioprotective, antidiabetic, antimetastatic, cardioprotective, antiatherosclerotic, antiallergic.

Dosage of Pharmaceutical Forms — Lentinula edodes

Powder — Lentinula edodes

Indications (Powder): Prostate cancer, breast cancer, stomach cancer, colon cancer, benign prostatic hyperplasia, hypercholesterolemia, arterial hypertension, immunodeficiency states, viral hepatitis, chronic hepatitis B, chronic hepatitis C, herpesvirus infections, tuberculosis, chronic recurrent respiratory infections, neurodegenerative diseases, chronic fatigue syndrome.

Standard Dosage (Powder): 1.5–2 grams of powder 2 times a day 30 minutes before meals, course 21–30 days.

Enhanced Dosage (Powder): 3 grams of powder 3 times a day for malignant neoplasms (breast cancer, prostate cancer, stomach cancer) and persistent viral infections (hepatitis B, herpesvirus infections).

Maximum Dosage (Powder): 5 grams 3 times a day for no more than 10 days consecutively for terminal oncological conditions and severe forms of immunodeficiency.

Preventive Dosage (Powder): 0.5–1 gram once a day in the morning 30 minutes before meals for 30 days. Recommended for patients with chronic viral load (human papillomavirus, hepatitis C), hypercholesterolemia, as well as patients over 50 years of age during periods of acute respiratory viral infections epidemics.

Pediatric Dosage (Powder): From 7 years of age and weight from 25 kg: 0.5 grams of powder once a day. Not recommended for children under 7 years of age due to the lack of clinical data.

Contraindications (Powder): Individual intolerance to mushrooms, severe forms of autoimmune diseases in the active phase. Data on contraindications during pregnancy, lactation, and childhood under 7 years of age have not been scientifically registered.

Side Effects (Powder): Registered: flatulence, diarrhea, decreased blood pressure in case of overdose. Allergic skin rashes are possible.

Adjustment for Patient Body Weight: For patients with body weight less than 60 kg, a reduction of dosage by 25% is recommended. For patients with body weight above 90 kg, an increase of dosage up to 20% of the standard is permissible.

Preparation Method (Powder): To prepare 100 grams of powder, 150 grams of dried fruit bodies of Lentinula edodes mushrooms are required. The mushrooms are washed under running water, dried at a temperature of 45–50 °C until brittle. After drying, they are ground into a micropowder with a fraction of less than 200 µm. Store in a hermetically closed glass container.

Storage Conditions and Shelf Life (Powder): Store in a dry, dark place at a temperature from +5 to +20 °C, away from sources of electromagnetic radiation. Shelf life — up to 18 months. After opening the package, use within 60 days.

Dry Extract — Lentinula edodes

Indications (Dry Extract): Breast cancer, stomach cancer, chronic hepatitis B, chronic hepatitis C, herpetic infection, chronic tonsillitis, immunodeficiency states, papillomavirus infection, atherosclerosis, neurodegenerative diseases.

Standard Dosage (Dry Extract): 500 mg of extract 2 times a day 20 minutes before meals. Course — 21 days with possible repetition after a 7-day break.

Enhanced Dosage (Dry Extract): 1 gram of extract 3 times a day for proven oncopathology, liver cirrhosis of viral etiology, herpesvirus load of type 4.

Maximum Dosage (Dry Extract): 1.5 grams 3 times a day for 7 days for inoperable tumor processes, HIV infection, pronounced viral load in hepatitis.

Preventive Dosage (Dry Extract): 250 mg once a day in a course of 30 days in autumn or spring. Suitable for patients over 45 years of age, persons with metabolic syndrome, in post-stress states.

Pediatric Dosage (Dry Extract): From 10 years of age, with body weight from 35 kg — 250 mg once a day, subject to consultation with a physician. Data for children under 10 years of age are absent.

Contraindications (Dry Extract): Individual hypersensitivity. Not recommended for patients with transplants. During pregnancy and lactation, use has not been studied. Contraindicated for children under 10 years of age.

Side Effects (Dry Extract): Dyspeptic phenomena, insomnia, headache are possible when the dose is exceeded.

Adjustment for Patient Body Weight: For patients with body weight less than 60 kg — 75% of the standard dose. For patients from 90 kg — 125% of the base dose.

Preparation Method (Dry Extract): 100 grams of extract are obtained from 1 kg of dry fruit bodies of mushrooms by the method of aqueous extraction followed by vacuum concentration. The raw material is ground, poured with water 1:10, extracted at a temperature of 85 °C for 3 hours. Filtered, thickened to a paste, dried by sublimation.

Storage Conditions and Shelf Life (Dry Extract): Store at a temperature not exceeding +25 °C, in a dry, dark place, in an airtight package. Shelf life — 24 months. After opening, use within 45 days.

Alcohol Tincture — Lentinula edodes

Indications (Alcohol Tincture): Papillomavirus infection, human herpesvirus type 1 and 2, chronic hepatitis B, chronic hepatitis C, chronic bronchitis, immunodeficiency states, initial stage of atherosclerosis, benign prostatic hyperplasia, chronic pharyngitis.

Standard Dosage (Alcohol Tincture): 20 drops (about 1 ml) 2 times a day, diluted in 50 ml of warm water, 30 minutes before meals. Course — 30 days.

Enhanced Dosage (Alcohol Tincture): 30 drops 3 times a day for active viral load (Epstein-Barr virus, hepatitis B and C, herpesviruses type 1–4), as well as for oncological diseases in remission.

Maximum Dosage (Alcohol Tincture): 40 drops 3 times a day, no more than 7 days consecutively, for acute exacerbation of chronic viral infection (hepatitis, cytomegalovirus, herpes) in adults with body weight over 70 kg.

Preventive Dosage (Alcohol Tincture): 10 drops once a day for 21 days. Recommended for persons who have had a viral infection, patients over 60 years of age, with chronic fatigue syndrome and stress-associated immunodeficiencies.

Pediatric Dosage (Alcohol Tincture): Contraindicated for children under 12 years of age. From 12 years of age — 5 drops diluted in water, once a day with weight not less than 40 kg.

Contraindications (Alcohol Tincture): Alcohol dependence, severe liver damage, epilepsy. Do not use in children under 12 years of age. There are no scientific data on safety during pregnancy and lactation.

Side Effects (Alcohol Tincture): With overdose, dizziness, weakness, increased sweating, nausea, allergic skin reactions are possible.

Adjustment for Patient Body Weight: Patients up to 60 kg — no more than 15 drops per intake. Patients above 80 kg — an increase of the dose up to 30 drops per intake is possible.

Preparation Method (Alcohol Tincture): To prepare 100 ml of tincture: 20 grams of ground dry fruit bodies are poured with 100 ml of 40% ethyl alcohol. Infuse in a glass container in a dark, cool place for 14 days with daily shaking. Strain through a sterile filter.

Storage Conditions and Shelf Life (Alcohol Tincture): Store in a hermetically closed dark glass container at a temperature from +5 to +25 °C. Shelf life — up to 3 years. After opening, use within 60 days, avoid exposure to sunlight.

Oil Infusion — Lentinula edodes

Indications (Oil Infusion): Psoriasis, atopic dermatitis, seborrheic dermatitis, contact dermatitis, eczema, dry exudative form of herpes, chronic pharyngitis, anogenital herpes.

Standard Dosage (Oil Infusion): Topically — 2 times a day on cleansed skin, in a thin layer, until absorbed. Internally — not used.

Enhanced Dosage (Oil Infusion): Topically — 3–4 times a day for pronounced itching, peeling, presence of herpetic rashes in the exacerbation stage.

Maximum Dosage (Oil Infusion): Up to 5 applications per day, locally on affected areas, course no more than 7 days consecutively. Used for herpetic rash, allergic dermatitis with weeping.

Preventive Dosage (Oil Infusion): Once a day on dry clean skin, in a course of 14–21 days. Used for chronic dermatitis, a tendency to herpes relapse, in the autumn-winter period.

Pediatric Dosage (Oil Infusion): From 5 years of age — once a day, locally. Use with caution, having previously applied to a small area of skin. Data on use under 5 years of age are absent.

Contraindications (Oil Infusion): Individual intolerance to components. Do not use for weeping forms of dermatitis with the addition of bacterial infection. Safety during pregnancy and lactation has not been confirmed.

Side Effects (Oil Infusion): Rarely: itching, burning, redness of the skin at the site of application. With overdose — a local allergic reaction is possible.

Adjustment for Patient Body Weight: Does not require correction — the form is topical. With excess body weight, the dosage is not increased.

Preparation Method (Oil Infusion): 100 grams of coconut oil are mixed with 20 grams of ground dry fruit body. Simmer in a water bath at a temperature of 45–50 °C for 3 hours. Cool, filter through gauze. Pour into a dark vial.

Storage Conditions and Shelf Life (Oil Infusion): Store at a temperature from +5 to +18 °C in a dark place. Shelf life — 6 months. After opening, use within 30 days, avoid water entering the package.

Cream — Lentinula edodes

Indications (Cream): Fungal skin infection, eczema, contact dermatitis, acne, perioral dermatitis, herpetic rashes in the healing stage.

Standard Dosage (Cream): Topically — 2 times a day on affected skin areas, in a thin layer, until completely absorbed. Course — from 10 to 21 days.

Enhanced Dosage (Cream): 3 times a day for pronounced peeling, itching, and chronic dermatoses with signs of lichenification.

Maximum Dosage (Cream): Up to 4 times a day for 5 days for acute inflammation, pronounced exacerbation of psoriasis, fungal skin lesion.

Preventive Dosage (Cream): Once a day, at night, for 14–28 days. Recommended for chronic dermatitis, seborrhea, increased skin sensitivity, recurrent herpes.

Pediatric Dosage (Cream): From 3 years of age — once a day locally. For children under 3 years of age, not recommended due to the lack of clinical data.

Contraindications (Cream): Open purulent wounds, allergic reaction to cream components. Data on safety during pregnancy and lactation have not been registered.

Side Effects (Cream): Local allergic reactions (itching, redness, rash) in case of hypersensitivity. With prolonged use — skin irritation.

Adjustment for Patient Body Weight: Correction is not required, the form is topical.

Preparation Method (Cream): For the preparation of 100 grams: oil infusion of Lentinula edodes — 20 g; aqueous extract of Lentinula edodes — 20 g; beeswax — 10 g; food coconut oil — 30 g; vegetable emulsifier — 5 g; distilled water — 15 g. Melt the wax and coconut oil in a water bath. Introduce the oil infusion and emulsifier, then slowly add the aqueous extract at a temperature of 50–55 °C, stirring constantly. Cool and pour into sterile containers.

Storage Conditions and Shelf Life (Cream): Store at a temperature from +5 to +12 °C, in a dark place, tightly closed. Shelf life — up to 3 months. After opening — use within 30 days.

Ointment — Lentinula edodes

Indications (Ointment): Fungal skin infection, anogenital herpes, dermatophytosis, foot mycosis, perianal fissures, eczema, psoriasis with pronounced peeling, chronic urticaria, dry form of atopic dermatitis.

Standard Dosage (Ointment): 1–2 times a day, topically on affected areas. Course — 14 days.

Enhanced Dosage (Ointment): 3 times a day for fungal lesions, mycoses, chronic eczema.

Maximum Dosage (Ointment): Up to 4 times a day locally, no more than 5 days consecutively for active manifestations of dermatophytosis and herpes.

Preventive Dosage (Ointment): Once a day for 10 days after the relief of symptoms of mycosis or dermatitis. Recommended for patients with recurrent forms of skin infections.

Pediatric Dosage (Ointment): From 6 years of age — once a day locally. Under 6 years of age — only after consultation with a physician.

Contraindications (Ointment): Acute purulent skin infections, individual intolerance. During pregnancy and lactation — with caution, data are insufficient.

Side Effects (Ointment): Skin irritation, erythema, contact dermatitis with prolonged use and individual hypersensitivity.

Adjustment for Patient Body Weight: Correction is not required.

Preparation Method (Ointment): For 100 grams: oil infusion of Lentinula edodes — 30 g; beeswax — 20 g; cocoa butter — 40 g; 10% propolis tincture — 5 g; D-panthenol — 5 g. Melt the cocoa butter and wax in a water bath, add the oil infusion and the remaining components. Stir until a homogeneous mass is obtained. Cool, pour into glass jars.

Storage Conditions and Shelf Life (Ointment): Store in a dark, cool place at a temperature of +5…+12 °C. Shelf life — 4 months. After opening — use within 30 days.

Serum — Lentinula edodes

Indications (Serum): Hyperpigmentation, age-related skin changes, couperose, decreased facial skin tone, acne, post-acne, seborrheic dermatitis, dry and tight skin, inflammatory dermatoses.

Standard Dosage (Serum): Apply 1–2 drops to cleansed skin of the face and neck once a day in the evening. Course — 28 days.

Enhanced Dosage (Serum): 2 times a day (morning and evening) 2 drops for pronounced signs of age-related skin, grade 2 acne, hyperpigmentation.

Maximum Dosage (Serum): 3 times a day 3 drops, no more than 10 days consecutively, for the active inflammatory phase of seborrheic dermatitis, acne with comedones and post-inflammatory hyperpigmentation.

Preventive Dosage (Serum): 1 drop at night, once a day, for 21 days. Suitable for the prevention of photoaging, couperose, seasonal skin dryness. Especially recommended for patients over 35 years of age.

Pediatric Dosage (Serum): Not used in children under 14 years of age. From 14 years of age — only as recommended by a dermatologist.

Contraindications (Serum): Individual sensitivity to serum components, active dermatitis, skin microtraumas, herpes in the active phase. During pregnancy and lactation — with caution, data are insufficient.

Side Effects (Serum): Rarely — a burning sensation, redness, skin peeling. An allergic reaction is possible in the presence of sensitivity.

Adjustment for Patient Body Weight: Not required, applied topically.

Preparation Method (Serum): For 100 ml: aqueous extract of Lentinula edodes — 30 ml; rose hydrolate — 40 ml; hyaluronic acid (1% gel) — 10 ml; natural preservative (rosemary extract) — 5 ml; aloe vera juice — 15 ml. The components are mixed in sterile dishes at a temperature not exceeding 25 °C, without heating. Poured into sterile bottles with a dispenser.

Storage Conditions and Shelf Life (Serum): Store in a refrigerator at a temperature of +4…+8 °C. Shelf life — 45 days. After opening — use within 30 days.

Lotion — Lentinula edodes

Indications (Lotion): Acne, oily seborrhea, inflammatory skin elements, enlarged pores, irritation after shaving, hyperhidrosis, skin irritation in folds, microbial eczemas.

Standard Dosage (Lotion): Wipe the skin 2 times a day with a cotton pad soaked in lotion. Course — 14 days.

Enhanced Dosage (Lotion): Up to 4 times a day for the active phase of acne, pronounced oily skin, a tendency to inflammations and pustular elements.

Maximum Dosage (Lotion): 6 times a day locally, no more than 5 days consecutively for pustular elements and irritation after depilation or shaving.

Preventive Dosage (Lotion): Once a day in the evening, in a course of 21 days. Indicated for patients with oily and problem skin, adolescents in puberty, as well as men with sensitive skin after shaving.

Pediatric Dosage (Lotion): From 10 years of age — once a day for oily skin. Only in the presence of indications.

Contraindications (Lotion): Open wounds, eczema in the weeping stage, individual intolerance to components. Data on use during pregnancy and lactation are insufficient.

Side Effects (Lotion): With frequent use — dry skin, peeling, irritation, feeling of tightness.

Adjustment for Patient Body Weight: Not required.

Preparation Method (Lotion): For 100 ml: aqueous infusion of Lentinula edodes — 50 ml; 10% calendula tincture — 20 ml; sage hydrolate — 20 ml; lactic acid — 1 ml; natural preservative — 2 ml; distilled water — 7 ml. Mix all components, keep in a refrigerator for 24 hours. Pour into dark vials with a dispenser cap.

Storage Conditions and Shelf Life (Lotion): Store in a refrigerator at a temperature from +4 to +8 °C. Shelf life — 30 days. After opening, use within 15 days.

Cosmetic Serum — Lentinula edodes

Indications (Cosmetic Serum): Fine wrinkles, dull complexion, photoaging, decreased skin elasticity, age-related pigmentation, couperose, post-acne, stress-induced skin aging.

Standard Dosage (Cosmetic Serum): 1–2 drops on the face and neck after cleansing, once a day in the evening, with light patting movements until absorbed. Course — 21–28 days.

Enhanced Dosage (Cosmetic Serum): 2–3 drops 2 times a day — morning and evening, for pronounced signs of aging, presence of hyperpigmentation, decreased skin tone.

Maximum Dosage (Cosmetic Serum): Up to 4 drops 2–3 times a day for active signs of gravitational aging, medium-depth wrinkles, photodermatosis. No more than 10 days consecutively.

Preventive Dosage (Cosmetic Serum): 1 drop at night, once a day, 2–3 courses per year of 21 days. Recommended for patients over 35 years of age living in megacities, with tired and dull skin.

Pediatric Dosage (Cosmetic Serum): Not used in childhood. Not recommended under 16 years of age.

Contraindications (Cosmetic Serum): Individual intolerance, open wounds, skin rashes in the exacerbation stage, herpetic vesicles. During pregnancy and lactation, use with caution.

Side Effects (Cosmetic Serum): Rarely — a tingling sensation, slight hyperemia, allergic rash in case of individual intolerance.

Adjustment for Patient Body Weight: Correction is not required.

Preparation Method (Cosmetic Serum): For 100 ml: aqueous extract of Lentinula edodes — 40 ml; allantoin — 1 g; lavender hydrolate — 20 ml; vitamin B3 (niacinamide) — 5 ml; 1% hyaluronic acid — 15 ml; plant-derived preservative — 3 ml; distilled water — 16 ml. Mix all components in sterile dishes at room temperature. Pour into bottles with a pipette dispenser.

Storage Conditions and Shelf Life (Cosmetic Serum): Store in a dark place at a temperature of +4…+8 °C. Shelf life — up to 45 days. After opening, use within 20 days.

Toxicity and Biosafety of Lentinula edodes

Lentinula edodes has a high biosafety profile and a long history of food and medicinal use. According to preclinical studies, acute toxicological testing on animals showed that extracts and powders obtained from the fruit bodies of Lentinula edodes do not cause toxic effects even with multiple excess of the standard therapeutic dosage.

The LD50 of the aqueous and alcohol extract of Lentinula edodes with oral administration to laboratory animals (mice and rats) was not reached at doses above 16 g/kg of body weight, which indicates the absence of acute toxicity. Repeated administration of extracts for 28 days also did not cause histopathological changes in internal organs.

The only registered side effect with excessive food consumption or use of extracts is a rare skin condition called "shiitake dermatitis," associated with a thermolabile component of lentinan, and manifested by linear rash in sensitive individuals.

Based on existing data, Lentinula edodes is classified as a non-toxic product with a high level of biosafety for oral and topical use.

Reference: https://www.ncbi.nlm.nih.gov/p...

Pharmacodynamics — Lentinula edodes

The pharmacodynamic properties of Lentinula edodes are due to the high content of polysaccharides (in particular, β-glucans), terpenes, sterins, amino acids, ergothioneine, and organic acids. The main mechanisms of action of the components of this taxon are realized at the systemic and tissue levels, including the immune, nervous, endocrine, digestive, and skin regulatory axes.

The immunomodulatory effect of Lentinula edodes is associated mainly with the polysaccharide lentinan — a β-(1→3)-glucan with branched β-(1→6)-chains. This biopolymer activates the innate and adaptive immune response by stimulating the functional activity of macrophages, natural killers, dendritic cells, and lymphocytes. The effect is realized through interaction with receptors of the Toll-like family (TLR2, TLR4) and β-glucan receptors on the surface of immunocompetent cells, followed by activation of signaling cascades, including NF-κB and MAPK.

At the level of regulation of inflammatory reactions, extracts of Lentinula edodes demonstrate suppression of the expression of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, due to the inhibition of cyclooxygenase-2 (COX-2) activity and suppression of lipid peroxidation. Thus, the taxon exhibits a pronounced anti-inflammatory and antioxidant effect, especially when acting on epithelial tissues and mucous membranes.

The antioxidant effect is due to the presence of phenolic compounds, ergothioneine, vitamin D2 (ergocalciferol), and trace elements. These compounds participate in the neutralization of free radicals, stabilization of membranes, and prevention of apoptosis induced by oxidative stress. Studies demonstrate an increase in the activity of antioxidant enzymes (superoxide dismutase, catalase) with the use of preparations based on this mushroom.

The effect on the endocrine system is realized mainly through the influence on lipid and carbohydrate metabolism. Lentinan and its accompanying compounds demonstrate the ability to modulate the activity of insulin receptors and enzymes involved in lipogenesis, due to which the level of triglycerides and cholesterol in blood serum decreases.

At the level of the digestive system, extracts of Lentinula edodes improve the state of the microbiota due to the prebiotic properties of polysaccharides. The growth of representatives of the Lactobacillus family is enhanced and the activity of opportunistic forms of Enterobacteriaceae is suppressed, which contributes to the restoration of the intestinal barrier and normalization of digestive processes.

Properties affecting neurohumoral regulation have also been identified. Some components of Lentinula edodes modulate the activity of GABA receptors and the level of dopamine in the limbic system, exhibiting a mild anxiolytic and adaptogenic potential.

The combination of these effects makes this taxon a biologically active base with proven effects on key cellular signaling pathways, immune and metabolic regulation.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271699/
https://www.sciencedirect.com/science/article/abs/pii/S0753332210003156
https://www.semanticscholar.or...

Pharmacokinetics — Lentinula edodes

The pharmacokinetic characteristics of preparations based on Lentinula edodes depend on the route of administration, the structure of active components, and the metabolic characteristics of the patient. The main routes of administration: oral (for powder, infusions, extracts), transdermal (ointment, cream, serum), as well as topical application to mucous membranes and skin.

With oral administration, the main absorbed components are water-soluble polysaccharides, amino acids, terpene compounds, and ergothioneine. Polysaccharides, including β-glucans, are largely resistant to the action of gastric and intestinal enzymes and are absorbed partially unchanged, as well as in the form of low-molecular fragments after microbial fermentation in the colon. The intestinal microflora plays a critical role in the biotransformation of these compounds, activating their immunomodulatory potential.

Some lipophilic components (for example, sterins, ergocalciferol) are actively absorbed in the small intestine in the presence of fats, which increases their bioavailability when taken with food. These substances are transported as part of chylomicrons through the lymphatic system and are distributed mainly in the liver, subcutaneous adipose tissue, skin, and other tissues.

After transdermal application (cream, ointment, oil infusion, serum), the penetration of active substances into the systemic bloodstream is limited and localized in the epidermis and dermis. Lipophilic components, in particular terpenes and phytoalkaloids, can penetrate into subcutaneous structures and exert a local effect, including antioxidant and anti-inflammatory effects.

The metabolism of water-soluble substances occurs mainly in the liver, with the participation of phases I and II (oxidation, glucuronidation, sulfation). Active metabolites of β-glucans can retain biological activity in the systemic circulation. Lipophilic compounds are excreted more slowly, undergoing bioactivation or detoxification by liver enzymes.

Excretion of metabolites is carried out mainly through the kidneys (urine) and to a lesser extent through bile. A small part can be excreted with sweat and through the lungs (volatile components of oil forms).

Powder forms have a slower onset of action but a longer systemic effect. Aqueous and alcohol extracts are characterized by faster absorption, but also a shorter period of activity. Transdermal forms act mainly locally, without significant systemic load.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9560133/
https://link.springer.com/article/10.1007/s00253-020-10589-5
https://pubmed.ncbi.nlm.nih.gov/19943748/

Mechanisms of Action and Scientific Rationale — Lentinula edodes

The biological activity of Lentinula edodes is realized through multiple molecular targets and signaling cascades mediated by its main active components — β-glucans, lentinan, terpenoids, ergothioneine, and phenolic compound derivatives. One of the central mechanisms is considered to be immunomodulation due to the interaction of β-(1→3)(1→6)-glucans with pattern-recognition receptors (PRRs), including Dectin-1, Toll-like receptors (TLR2, TLR4), and CD11b/CD18. These interactions initiate phagocytosis, activation of macrophages and dendritic cells, secretion of pro-inflammatory and regulatory cytokines (IL-2, IL-6, TNF-α, IFN-γ), as well as stimulation of T-lymphocyte maturation.

Signaling cascades associated with nuclear factor NF-κB, MAPK/ERK, and PI3K/Akt play an important role. Interaction with these pathways contributes to an increase in the expression of major histocompatibility complex class II molecules, activation of translation of anti-inflammatory proteins, inhibition of apoptosis, and tissue regeneration. Lentinan additionally inhibits COX-2 activity and reduces the levels of prostaglandin PGE2 synthesis, mediating an anti-inflammatory effect.

The antioxidant activity of Lentinula edodes is provided by the content of ergothioneine and phenolic metabolites, which have the ability to neutralize reactive oxygen species (ROS), suppress lipid peroxidation, and increase the activity of endogenous enzymes (catalase, superoxide dismutase, glutathione peroxidase). This leads to the protection of cell membranes from oxidative damage and a decrease in the level of tissue stress.

Effects on metabolic regulatory axes are observed: induction of insulin receptor expression and a decrease in α-glucosidase activity, which indicates a potential effect on carbohydrate metabolism. The effect on lipid metabolism is realized through the activation of AMP-dependent protein kinase (AMPK) and modulation of cholesterol synthesis through inhibition of HMG-CoA reductase.

At the level of cellular neuroimmune regulation, the effect of Lentinula edodes on the level of serotonin and dopamine in the hypothalamic-pituitary system, as well as on the expression of GABA and NMDA receptors, has been found, which confirms participation in neurotrophic and sedative processes. There are data on a decrease in acetylcholinesterase activity, which may be associated with an improvement in cognitive function.

Mushroom extracts also affect endothelial cells, reducing the expression of VCAM-1 and ICAM-1, which indicates potential in the regulation of vascular tone and a decrease in the inflammatory response at the capillary level. In a number of models, inhibition of angiogenesis due to suppression of VEGF signaling has been confirmed, especially at high concentrations of polysaccharides.

Thus, Lentinula edodes acts through a wide network of receptors and enzyme systems, having a complex effect on the immune, endocrine, antioxidant, and neuroregulatory axes, which has been confirmed by both in vitro and in vivo models.

References:
https://www.ncbi.nlm.nih.gov/p...
https://pubmed.ncbi.nlm.nih.go...
https://www.sciencedirect.com/...
https://www.semanticscholar.or...

Synergy — Lentinula edodes

Scientific publications demonstrate a pronounced pharmacological synergy between Lentinula edodes and several classes of biologically active substances of natural origin. The potentiation of the immunomodulatory effect in combination with other β-glucan-containing mushrooms, including Grifola frondosa and Ganoderma lucidum, has been most reliably established. With combined use, additive and potentiating activation of macrophages, an increase in the production of IL-12 and IFN-γ, as well as an enhancement of phagocytic activity are observed.

Synergy with plants rich in flavonoids (for example, Camellia sinensis, Curcuma longa) is expressed in the enhancement of antioxidant activity. Experimental data confirm the modulating effect of Lentinula edodes on the expression of antioxidant defense enzymes when combined with polyphenols, especially under conditions of oxidative stress in vitro. Such a combination demonstrates synergistic suppression of free radical production and a decrease in damage to membrane structures.

The combined use of Lentinula edodes extracts with omega-3 fatty acids (for example, from Perilla frutescens oil) enhances anti-inflammatory effects due to the complex suppression of pro-inflammatory cytokines (IL-1β, TNF-α) and inhibition of COX-2. A systemic tissue-specific effect is noted, especially pronounced in epithelial and endothelial cells.

Of interest is the interaction with adaptogens (for example, Eleutherococcus senticosus), in which the properties of Lentinula edodes aimed at stabilizing the function of the hypothalamic-pituitary-adrenal axis are enhanced. Combined use demonstrates an increase in the body's resistance to stress-induced metabolic disorders, mediated through JAK/STAT and HPA regulation.

In addition, in vitro, the modulating activity of Lentinula edodes has been shown when used together with vitamin D and selenium-containing complexes. These combinations contribute to the enhancement of apoptosis regulation and activation of immune defense through the p53 and NF-κB signaling pathways.

Thus, Lentinula edodes demonstrates both potentiating and modulating types of synergy with biologically active plant substances, fatty acids, trace elements, and other medicinal mushrooms, which confirms its importance in combined pharmacological systems.

References:
https://www.sciencedirect.com/...
https://pubmed.ncbi.nlm.nih.go...
https://www.semanticscholar.or...
https://www.ncbi.nlm.nih.gov/p...

Geography of Use and Traditional Medicine — Lentinula edodes

Lentinula edodes, better known by its Japanese name "shiitake," has an extensive geography of traditional use covering East and Southeast Asia, especially the territories of Japan, China, Korea, Vietnam, and Thailand. The first mentions of its use are recorded in Chinese treatises of the Song Dynasty (10th–13th centuries), where it was called "xianggu" (香菇 — fragrant mushroom) and was considered one of the means for "strengthening vital energy." In Japan, it was cultivated on oak logs already in the 14th century, and in written sources it is mentioned as part of the monastic diet and health practices of Buddhist schools.

In Chinese folk medicine, shiitake was used in the form of decoctions, tinctures, steam inhalations, and food decoctions on rice wine. The mushroom was boiled with astragalus roots, lotus seeds, or Baikal skullcap. It was believed that its regular consumption contributes to the restoration of the balance of "qi" energy and cleansing the body of "heat" and "dampness." The Korean tradition complements this with the use of shiitake in infusions on Korean pine, where it was used for the purpose of "longevity and strengthening the spirit."

In Vietnam and Laos, the mushroom was used in dried form in collections with cinnamon bark and turmeric root, brewed as a ritual drink for revival after illness. In the northern provinces of Thailand, especially in the culture of the Hmong people, shiitake was considered the "mushroom of the forest spirit." Its dried fruit bodies were sewn into amulets, hung at the entrance to the house for protection from the evil eye and diseases. In ritual practice, these groups also used the smoke from the smoldering of shiitake mixed with sandalwood to cleanse the house of negative energy and evil spirits.

In the indigenous ethnic traditions of southern China and the island of Taiwan, the mushroom was used as part of funeral rituals — it was placed in bags next to the body of the deceased, as a symbol of transition and protection in the afterlife. Among Japanese monks of the Edo period, shiitake was included in the diet as a ritual product contributing to "clarity of thought and calmness of heart" during meditation.

There is also a practice of using shiitake extracts in cosmetic and cleansing rituals among some mountain peoples of Burma, where aqueous infusions were used for ablutions and rubdowns before initiation ceremonies.

Thus, Lentinula edodes occupies an important place in the ethnocultural traditions of Asia — as a medicinal, ritual, and food mushroom with deep historical symbolism and use in various forms and contexts.