Propolis

Propolis

Product Name: Прополис, Propolis, Propolis, Propóleo, Propolis, صمغ النحل, กาวผึ้ง, Propolis, Прополис, Propolis, Прополис, Propolis, Propoliss, Прополіс, Propolis

Synonyms: пчелиный клей, bee glue, Bienenkittharz, propóleos, propolis végétal, صمغ البروبوليس, น้ำผึ้งกาว, клей пчелиный, bee putty, kittharz

Parts used: resin (bee glue), wax components, plant resinous secretions, pollen inclusions, essential oils, mechanical plant impurities

Main indications for the use of Propolis: bacterial respiratory tract infections, viral upper respiratory tract infections, mucosal candidiasis, periodontitis, stomatitis, pharyngitis, tonsillitis, bronchitis, pneumonia, gastritis, gastric ulcer, duodenal ulcer, intestinal dysbiosis, dermatomycosis, eczema, psoriasis, seborrheic dermatitis, wound infections, burn skin lesions, trophic ulcers, herpes infection, urethritis, prostatitis, adnexitis, cervical erosion.

Indications for the use of Propolis in mixtures and complexes: arterial hypertension, type 2 diabetes mellitus, hyperlipidemia, metabolic syndrome, chronic obstructive pulmonary disease, bronchial asthma, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, chronic viral hepatitis, liver cirrhosis, chronic renal failure, oncological diseases, pulmonary tuberculosis, immunodeficiency states, chronic fatigue syndrome.

Main pharmacological properties of Propolis: antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective, wound-healing, analgesic, antitumor, cardioprotective, antiatherogenic, adaptogenic, desensitizing, antispasmodic, hypolipidemic, antimutagenic, reparative, local anesthetic, antiseptic, radioprotective.

Dosage of pharmaceutical forms — Propolis

Powder — Propolis

Indications (Powder): stomatitis, periodontitis, tonsillitis, pharyngitis, gastritis, gastric ulcer, duodenal ulcer, mucosal candidiasis, eczema, seborrheic dermatitis, trophic ulcers, herpes infection.

Standard Dosage (Powder): orally at 0.5–1.0 gram of powder 2 times a day, course of treatment 10–14 days.

Enhanced Dosage (Powder): orally at 1.5 grams of powder 2 times a day for gastric ulcer, duodenal ulcer, chronic herpes infection.

Maximum Dosage (Powder): orally at 2.0 grams of powder 2 times a day, for severe trophic ulcers, chronic mucosal candidiasis, widespread eczema.

Preventive Dosage (Powder): orally at 0.3 grams of powder once a day in courses of 20 days, for patients with chronic gastritis, periodontitis, chronic pharyngitis, it is recommended to repeat the course every 3 months.

Pediatric Dosage (Powder): orally at 0.1–0.3 grams of powder once a day, from 6 years of age, child's body weight not less than 20 kilograms, child's gender is irrelevant.

Contraindications (Powder): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 6 years of age have not been scientifically registered.

Side Effects (Powder): allergic skin reactions, itching, erythema, nausea upon overdose.

Adjustment for Patient Body Weight: for body weight less than 60 kilograms, reduce the dose by 20%; for body weight more than 60 kilograms, use the full dose without correction.

Preparation method (Powder): Powder take 100 grams of purified dry propolis, freeze at minus 18 degrees Celsius for 2 hours, grind into powder in a ceramic mortar, sieve through a sieve with a mesh size of 0.5 millimeters, package in an airtight dark glass container.

Storage Conditions and Shelf Life (Powder): Powder store in a dry, dark place at a temperature not exceeding 20 degrees Celsius, protect from exposure to electromagnetic radiation; shelf life is 24 months; after opening the package, use within 6 months.

Dry Extract — Propolis

Indications (Dry Extract): bacterial respiratory tract infections, pneumonia, bronchitis, intestinal dysbiosis, urethritis, prostatitis, adnexitis, cervical erosion, dermatomycosis, psoriasis.

Standard Dosage (Dry Extract): orally at 200 milligrams of dry extract 2 times a day, course of 14 days.

Enhanced Dosage (Dry Extract): orally at 400 milligrams of dry extract 2 times a day for pneumonia, chronic bronchitis, prostatitis.

Maximum Dosage (Dry Extract): orally at 600 milligrams of dry extract 2 times a day for severe cases of cervical erosion, dermatomycosis, psoriasis.

Preventive Dosage (Dry Extract): orally at 100 milligrams of dry extract once a day in a course of 21 days, for patients with chronic bronchitis, periodontitis, immunodeficiency states, repeat the course twice a year.

Pediatric Dosage (Dry Extract): orally at 50 milligrams of dry extract once a day, from 7 years of age, child's body weight not less than 25 kilograms.

Contraindications (Dry Extract): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 7 years of age have not been scientifically registered.

Side Effects (Dry Extract): skin rash, swelling of mucous membranes upon overdose.

Adjustment for Patient Body Weight: for body weight less than 60 kilograms, reduce the dose by 25%; for body weight more than 80 kilograms, a dose increase of 20% is possible.

Preparation method (Dry Extract): Dry Extract grind 500 grams of dry propolis, extract with 70% ethanol 1000 milliliters at a temperature of 40 degrees Celsius for 72 hours, filter, evaporate the solution in a water bath at a temperature not exceeding 50 degrees Celsius to a dry residue, ensure the complete disappearance of the ethanol odor, residual ethanol content should not exceed 50 ppm, grind the obtained dry extract to a powder state, bring the mass to 100 grams.

Storage Conditions and Shelf Life (Dry Extract): Dry Extract store in an airtight dark glass container at a temperature of 15–20 degrees Celsius, protect from direct sunlight and electromagnetic radiation; shelf life is 24 months; after opening the package, use within 6 months.

Tincture — Propolis

Indications (Tincture): pharyngitis, tonsillitis, stomatitis, periodontitis, bronchitis, pneumonia, gastritis, gastric ulcer, duodenal ulcer, urethritis, adnexitis, cervical erosion, mucosal candidiasis, dermatomycosis, eczema.

Standard Dosage (Tincture): orally at 20 drops of 10% alcohol tincture, diluted in 50 milliliters of water, 2 times a day, course of 14 days.

Enhanced Dosage (Tincture): orally at 30 drops of 10% alcohol tincture, diluted in 50 milliliters of water, 2 times a day for pneumonia, chronic bronchitis, cervical erosion.

Maximum Dosage (Tincture): orally at 40 drops of 10% alcohol tincture, diluted in 100 milliliters of water, 3 times a day for severe forms of mucosal candidiasis, trophic ulcers, widespread eczema.

Preventive Dosage (Tincture): orally at 15 drops of 10% alcohol tincture, diluted in water, once a day in a course of 20 days for patients with chronic pharyngitis, periodontitis, gastritis, repeat the course twice a year.

Pediatric Dosage (Tincture): orally at 5–10 drops of 10% alcohol tincture, diluted in water or milk, once a day, from 7 years of age, body weight not less than 25 kilograms.

Contraindications (Tincture): allergy to bee products, chronic alcoholism, severe liver diseases, data on contraindications during pregnancy, lactation and in children under 7 years of age have not been scientifically registered.

Side Effects (Tincture): allergic skin reactions, burning of mucous membranes, nausea upon overdose.

Adjustment for Patient Body Weight: for body weight less than 60 kilograms, reduce the dose by 20%; for body weight more than 80 kilograms, increase the dose by 20%.

Preparation method (Tincture): Alcohol Tincture grind 20 grams of dry propolis, add 100 milliliters of 70% ethanol, infuse for 7 days at a temperature of 20–25 degrees Celsius in a dark place, shake daily, filter through a paper filter, bring the volume to 100 milliliters, ethanol is used only for extraction and is a component of the finished preparation in diluted form.

Storage Conditions and Shelf Life (Tincture): Alcohol Tincture store in a tightly closed dark glass container at a temperature of 15–20 degrees Celsius, protect from sunlight and electromagnetic radiation; shelf life is 24 months; after opening, use within 6 months.

Oil Infusion — Propolis

Indications (Oil Infusion): wound infections, burn skin lesions, trophic ulcers, eczema, psoriasis, seborrheic dermatitis, herpes infection of the skin, urethritis, prostatitis, adnexitis, cervical erosion.

Standard Dosage (Oil Infusion): externally apply a thin layer to affected skin areas 2 times a day, course of 14–21 days.

Enhanced Dosage (Oil Infusion): externally apply a thin layer to affected skin areas 3 times a day for trophic ulcers, burn skin lesions, herpes infection of the skin.

Maximum Dosage (Oil Infusion): externally apply 4 times a day for severe trophic ulcers, widespread eczema, psoriasis.

Preventive Dosage (Oil Infusion): externally apply once a day to the skin of the face and mucous membranes for the prevention of recurrent herpes, seborrheic dermatitis, recommended for patients with chronic dermatological diseases in courses of 14 days twice a year.

Pediatric Dosage (Oil Infusion): externally apply once a day to affected skin areas for children from 3 years of age, body weight not less than 15 kilograms.

Contraindications (Oil Infusion): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 3 years of age have not been scientifically registered.

Side Effects (Oil Infusion): local skin irritation, itching, hyperemia upon overdose.

Adjustment for Patient Body Weight: no correction required, as the form is for external use.

Preparation method (Oil Infusion): Oil Infusion grind 20 grams of dry propolis, pour 100 milliliters of coconut oil, heat in a water bath at a temperature of 40 degrees Celsius for 3 hours, filter through two layers of cheesecloth, bring the mass to 100 grams, the finished product should be homogeneous, without the smell of solvents.

Storage Conditions and Shelf Life (Oil Infusion): Oil Infusion store in a tightly closed dark glass container at a temperature of 4–8 degrees Celsius, protect from sunlight and electromagnetic radiation; shelf life is 12 months; after opening, use within 30 days.

Vaginal Suppository — Propolis

Indications (Vaginal Suppository): vaginal candidiasis, bacterial vaginosis, cervical erosion, cervicitis, adnexitis, trichomonal colpitis.

Standard Dosage (Vaginal Suppository): one suppository of 500 milligrams at night, course of 10 days.

Enhanced Dosage (Vaginal Suppository): one suppository of 500 milligrams 2 times a day for cervical erosion, adnexitis, trichomonal colpitis.

Maximum Dosage (Vaginal Suppository): one suppository of 1000 milligrams 2 times a day for severe cases of vaginal candidiasis and cervicitis.

Preventive Dosage (Vaginal Suppository): one suppository of 500 milligrams 2 times a week in a course of 1 month for the prevention of recurrent bacterial vaginosis and candidiasis in women with chronic inflammatory diseases of the pelvic organs.

Pediatric Dosage (Vaginal Suppository): not used, safety data in children and adolescents have not been scientifically registered.

Contraindications (Vaginal Suppository): allergy to bee products, data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Vaginal Suppository): local burning, itching, mucosal hyperemia upon overdose.

Adjustment for Patient Body Weight: dose adjustment is not required.

Preparation method (Vaginal Suppository): Vaginal Suppository grind 20 grams of dry propolis, dissolve in 50 milliliters of 70% ethanol, infuse for 48 hours at a temperature of 20 degrees Celsius, filter, evaporate in a water bath at a temperature not exceeding 50 degrees Celsius to a dry residue, ensure the disappearance of the ethanol odor, residual content not more than 50 ppm, mix the dry extract with 80 grams of coconut oil and 20 grams of beeswax, melt at a temperature of 40 degrees Celsius, pour into suppository molds of 2 grams, cool until solid.

Storage Conditions and Shelf Life (Vaginal Suppository): Vaginal Suppository store in a refrigerator at a temperature of 4–8 degrees Celsius, protect from sunlight and electromagnetic radiation; shelf life is 12 months; after opening, use within 14 days.

Rectal Suppository — Propolis

Indications (Rectal Suppository): hemorrhoids, proctitis, anal fissure, chronic prostatitis, benign prostatic hyperplasia, chronic colitis.

Standard Dosage (Rectal Suppository): one suppository of 500 milligrams at night, course of 10–14 days.

Enhanced Dosage (Rectal Suppository): one suppository of 500 milligrams 2 times a day for prostatitis and hemorrhoids of II–III degree.

Maximum Dosage (Rectal Suppository): one suppository of 1000 milligrams 2 times a day for pronounced inflammation of the rectum, chronic prostatitis, benign prostatic hyperplasia.

Preventive Dosage (Rectal Suppository): one suppository of 500 milligrams every other day in a course of 1 month for patients with chronic colitis and chronic hemorrhoids, repeat the course twice a year.

Pediatric Dosage (Rectal Suppository): one suppository of 250 milligrams once a day for children from 6 years of age, body weight not less than 20 kilograms.

Contraindications (Rectal Suppository): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 6 years of age have not been scientifically registered.

Side Effects (Rectal Suppository): itching, burning, increased frequency of defecation upon overdose.

Adjustment for Patient Body Weight: for body weight less than 60 kilograms, use suppositories of 250 milligrams; for body weight more than 60 kilograms, use the full dose.

Preparation method (Rectal Suppository): Rectal Suppository grind 20 grams of dry propolis, extract with 100 milliliters of 70% ethanol, infuse for 72 hours, filter, evaporate in a water bath at a temperature of 50 degrees Celsius to a dry residue, ensure the disappearance of the ethanol odor, residual content not more than 50 ppm, mix the dry extract with 85 grams of coconut oil and 15 grams of cocoa butter, melt at a temperature of 38–40 degrees Celsius, pour into suppository molds of 2 grams, cool.

Storage Conditions and Shelf Life (Rectal Suppository): Rectal Suppository store in a refrigerator at a temperature of 4–8 degrees Celsius, protect from light and electromagnetic radiation; shelf life is 12 months; after opening, use within 14 days.

Nasal Drops — Propolis

Indications (Nasal Drops): acute rhinitis, chronic rhinitis, sinusitis, adenoiditis, allergic rhinitis, rhinosinusitis.

Standard Dosage (Nasal Drops): instill 2 drops 2 times a day into each nasal passage in a course of 7–10 days.

Enhanced Dosage (Nasal Drops): instill 3 drops 3 times a day for chronic rhinitis and sinusitis.

Maximum Dosage (Nasal Drops): instill 4 drops 3 times a day for adenoiditis and severe rhinosinusitis.

Preventive Dosage (Nasal Drops): instill 1 drop once a day in a course of 14 days for the prevention of seasonal allergic rhinitis and recurrent sinusitis, repeat the course in spring and autumn.

Pediatric Dosage (Nasal Drops): 1 drop 2 times a day for children from 5 years of age, body weight not less than 18 kilograms.

Contraindications (Nasal Drops): allergy to bee products, pronounced allergic reaction to plant pollen, data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Nasal Drops): burning of the nasal mucosa, sneezing, rhinorrhea upon overdose.

Adjustment for Patient Body Weight: for body weight less than 60 kilograms, reduce the dose by 20%; for body weight more than 80 kilograms, a dose increase of 20% is possible.

Preparation method (Nasal Drops): Nasal Drops grind 10 grams of dry propolis, extract with 50 milliliters of 70% ethanol at room temperature for 48 hours, filter, evaporate in a water bath at a temperature of 45 degrees Celsius until the smell of ethanol completely disappears, residual content not more than 50 ppm, mix the dry extract with 50 grams of coconut oil, bring the mass to 100 grams, mix thoroughly until homogeneous.

Storage Conditions and Shelf Life (Nasal Drops): Nasal Drops store in a dark container at a temperature of 4–8 degrees Celsius; shelf life is 6 months; after opening, use within 30 days.

Ointment — Propolis

Indications (Ointment): dermatomycosis, eczema, psoriasis, seborrheic dermatitis, wound infections, trophic ulcers, burn skin lesions, herpes infection of the skin.

Standard Dosage (Ointment): apply a thin layer to affected skin areas 2 times a day, course of treatment 10–14 days.

Enhanced Dosage (Ointment): apply 3 times a day for trophic ulcers, burn skin lesions, chronic eczema.

Maximum Dosage (Ointment): apply 4 times a day for severe psoriasis, extensive trophic ulcers, chronic dermatomycosis.

Preventive Dosage (Ointment): apply once a day in courses of 14 days for the prevention of recurrent herpes and seborrheic dermatitis, recommended for patients with chronic dermatological diseases, repeat the course twice a year.

Pediatric Dosage (Ointment): apply once a day for children from 3 years of age, body weight not less than 15 kilograms.

Contraindications (Ointment): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 3 years of age have not been scientifically registered.

Side Effects (Ointment): local skin irritation, itching, hyperemia upon overdose.

Adjustment for Patient Body Weight: dose adjustment is not required, as the form is for external use.

Preparation method (Ointment): Ointment grind 20 grams of dry propolis, extract with 100 milliliters of 70% ethanol at room temperature for 72 hours, filter, evaporate in a water bath at a temperature not exceeding 50 degrees Celsius to a dry residue, ensure the disappearance of the ethanol odor, residual content not more than 50 ppm, mix the dry extract with 70 grams of coconut oil and 10 grams of beeswax, bring the mass to 100 grams, mix thoroughly at a temperature of 40 degrees Celsius until a homogeneous consistency.

Storage Conditions and Shelf Life (Ointment): Ointment store in a tightly closed dark glass container at a temperature of 4–8 degrees Celsius, protect from sunlight and electromagnetic radiation; shelf life is 12 months; after opening, use within 30 days.

Cream — Propolis

Indications (Cream): eczema, psoriasis, seborrheic dermatitis, acne, rosacea, trophic ulcers, herpes infection of the skin, burn skin lesions.

Standard Dosage (Cream): apply a thin layer to affected skin areas 2 times a day, course of treatment 14–21 days.

Enhanced Dosage (Cream): apply 3 times a day for severe cases of acne, rosacea, trophic ulcers, herpes infection of the skin.

Maximum Dosage (Cream): apply 4 times a day for extensive psoriasis, eczema, seborrheic dermatitis.

Preventive Dosage (Cream): apply once a day in courses of 14 days for the prevention of recurrent acne and seborrheic dermatitis, recommended for patients with chronic dermatological diseases, repeat the course twice a year.

Pediatric Dosage (Cream): apply once a day for children from 5 years of age, body weight not less than 18 kilograms.

Contraindications (Cream): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 5 years of age have not been scientifically registered.

Side Effects (Cream): local skin irritation, itching, burning, hyperemia upon overdose.

Adjustment for Patient Body Weight: dose adjustment is not required, as the form is for external use.

Preparation method (Cream): Cream grind 15 grams of dry propolis, extract with 80 milliliters of 70% ethanol at room temperature for 72 hours, filter, evaporate in a water bath at a temperature of 45 degrees Celsius until the ethanol smell is completely removed, residual content not more than 50 ppm, mix the dry extract with 60 grams of coconut oil, 20 grams of beeswax, and 5 grams of glycerin, mix thoroughly at a temperature of 40 degrees Celsius until a homogeneous emulsion mass, bring the mass to 100 grams.

Storage Conditions and Shelf Life (Cream): Cream store in a dark container at a temperature of 4–8 degrees Celsius, protect from sunlight and electromagnetic radiation; shelf life is 12 months; after opening, use within 30 days.

Cosmetics — Propolis

Indications (Cosmetics): seborrheic dermatitis, acne, post-acne, rosacea, premature skin aging, hyperpigmentation, rosacea (couperose), dry skin, skin damage from solar radiation.

Standard Dosage (Cosmetics): apply to the skin of the face or body 1–2 times a day as part of finished cosmetic products (lotion, cream, mask), course of application 30 days.

Enhanced Dosage (Cosmetics): apply 2–3 times a day for pronounced acne, post-acne, rosacea, seborrheic dermatitis.

Maximum Dosage (Cosmetics): apply up to 4 times a day for severe hyperpigmentation and pronounced rosacea (couperose).

Preventive Dosage (Cosmetics): apply once a day in courses of 20 days for the prevention of premature skin aging and dry skin, recommended for women over 35 years old and patients with chronic dermatological problems, repeat the course 3 times a year.

Pediatric Dosage (Cosmetics): external use as part of cosmetic products is allowed for children from 3 years of age, once a day, for dry skin and a tendency to seborrheic dermatitis.

Contraindications (Cosmetics): allergy to bee products, data on contraindications during pregnancy, lactation and in children under 3 years of age have not been scientifically registered.

Side Effects (Cosmetics): skin irritation, itching, hyperemia, skin peeling upon overdose.

Adjustment for Patient Body Weight: no correction required, as the form is for external use.

Preparation method (Cosmetics): Cosmetics grind 10 grams of dry propolis, extract with 50 milliliters of 70% ethanol for 48 hours, filter, evaporate in a water bath at a temperature of 45 degrees Celsius until the smell of ethanol completely disappears, residual content not more than 50 ppm, mix the obtained dry extract with 50 grams of coconut oil, 30 grams of aloe gel, and 10 grams of beeswax, bring the mass to 100 grams, mix thoroughly at a temperature of 35–40 degrees Celsius, pour into cosmetic containers.

Storage Conditions and Shelf Life (Cosmetics): Cosmetics store at a temperature of 4–8 degrees Celsius in dark containers, protect from sunlight and electromagnetic radiation; shelf life is 6 months; after opening, use within 30 days.

Toxicity and Biosafety — Propolis

Brief summary: According to preclinical studies, propolis and its ethanolic/ hydroalcoholic extracts have low acute toxicity (for most samples, the oral LD₅₀ in rodents ranges from ≥2000 to >7000 mg/kg body weight). In 90-day and longer experiments, an absence of carcinogenicity and minimal morphological changes in organs are noted, but reversible biochemical shifts in the liver and kidneys and pronounced skin sensitization in humans (contact dermatitis) are possible. According to the EPA/WHO classification, with an LD₅₀ > 5000 mg/kg, such samples are classified as "practically non-toxic" (Category IV). Acute toxicity (LD₅₀)

• Mice, oral, propolis extract: LD₅₀ > 7.34 g/kg; dermal on rabbit — non-irritating upon repeated application. Conclusion: low toxicity.

Reference to study: Arvouet-Grand A., Lejeune B., Bastide P., Pourrat A., Privat A.M., Legret P. (1993) Propolis extract. I. Acute toxicity and determination of acute primary cutaneous irritation index. Journal de Pharmacie de Belgique, 48(3):165--170. (https://pubmed.ncbi.nlm.nih.go...)

• Rats, oral, hydroethanolic extract of Brazilian red propolis (HERP): at a limit dose of 300 mg/kg, no lethality; according to OECD 420 method, LD₅₀ calculated as > 300 mg/kg; in a subchronic regimen (10–200 mg/kg, 28 days), toxic signals were noted in males at 200 mg/kg (estrogen-like activity of isoflavones likely).

Reference to study: da Silva R.O. et al. (2015) Acute and sub-acute oral toxicity of Brazilian red propolis in rats. Journal of Ethnopharmacology, 170:66–71. (https://pubmed.ncbi.nlm.nih.go...)

• Summary for different samples: in mice, oral LD₅₀ for propolis extracts is 2000–7300 mg/kg; in rats, for main flavonoids, it is 4000–8000 mg/kg.

Reference to study: Kakehashi A. et al. (2016) Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats. PLoS ONE, 11(7):e0158654. (https://pubmed.ncbi.nlm.nih.go...)

Long-term/chronic toxicity

• 2-year carcinogenic test in Wistar Hannover rats: dietary administration of 0.5% and 2.5% EEP (~1000–2000 mg/kg/day) did not increase tumor frequency; anti-inflammatory effects and improved survival were noted.

Reference to study: Kakehashi A. et al. (2016) PLoS ONE, 11(7):e0158654. (https://pubmed.ncbi.nlm.nih.go...)

• 90-day administration of Brazilian red propolis: 1000 mg/kg/day (Wistar Hannover rats) — without histopathological changes in organs, but with changes in water and food consumption, body weight, and liver/kidney biochemical parameters (mainly in males). Single dose of 2000 mg/kg — no acute toxicity.

Reference to study: Aldana-Mejía J.A. et al. (2023) Genotoxicity and toxicological evaluations of Brazilian red propolis oral ingestion in a preclinical rodent model. Journal of Ethnopharmacology, 303:115920. (https://pubmed.ncbi.nlm.nih.go...)

• Comparison of extractants (90 days): in rats, pronounced kidney changes and increases in liver enzymes are more characteristic of ethanolic and propylene glycol extracts; the olive oil extract demonstrated better safety profiles.

Reference to study: Silici S. et al. (2024) Effects of short- and long-term use of propolis extracts on liver and kidney in rats. Veterinary Medicine and Science. (https://pmc.ncbi.nlm.nih.gov/a...)

Genotoxicity and mutagenicity

• Micronucleus test in mice (500–2000 mg/kg, oral): no genotoxic effect detected; in the 90-day study at 1000 mg/kg — without organ histopathology.

Reference to study: Aldana-Mejía J.A. et al. (2023) Journal of Ethnopharmacology, 303:115920. (https://pubmed.ncbi.nlm.nih.go...)

• Plant test system Allium cepa: for ethanolic extract of Brazilian green propolis — absence of geno/mutagenicity, pronounced antigenotoxicity/antimutagenicity.

Reference to study: Roberto M.M. et al. (2016) Genetics and Molecular Biology, 39(2):257–269. (https://pmc.ncbi.nlm.nih.gov/a...)

• Reviews and preclinical data on Ames/Salmonella and other systems generally indicate the antimutagenic potential of propolis and the absence of its own mutagenic properties at tested concentrations.

Reference to study: Burdock G.A. (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology, 36(4):347–363. (https://people.fmarion.edu/gpr...)

Sensitization/allergy in humans

• Contact allergy to propolis occurs in patients with dermatitis (positive patch tests ~1–6% in European series; record higher in individual cohorts). Clinically — contact dermatitis, cheilitis, perioral eczema; systemic reactions have been described when taking supplements.

References to studies:
— Nyman G.S.A. et al. (2021) Patch Testing with Propolis of Different Geographical Origins in a Baseline Series. Acta Dermato-Venereologica. (https://pubmed.ncbi.nlm.nih.go...)
— Walgrave S.E. et al. (2005) Allergic contact dermatitis from propolis. American Journal of Contact Dermatitis, 16(3):145–149. (https://pubmed.ncbi.nlm.nih.go...)
— Cho E. et al. (2011) Systemic Contact Dermatitis from Propolis Ingestion. Annals of Dermatology, 23(Suppl 1):S108–S111. (https://pmc.ncbi.nlm.nih.gov/a...)

Hazard classification assessment

• Threshold values for acute oral toxicity (EPA/WHO/GHS): Category IV ("practically non-toxic") — LD₅₀ > 5000 mg/kg; Category III ("slightly toxic") — > 500 – ≤ 5000 mg/kg. Most data on propolis falls into these two low categories, which corresponds to the overall assessment of "low toxicity," while individual extracts (e.g., red propolis) may exhibit dose-dependent biochemical effects.

Reference to document: U.S. EPA. Label Review Manual. Chapter 7: Precautionary Statements. Table "Toxicity Categories". (https://www.epa.gov/sites/defa...)

Final assessment according to WHO/regulatory criteria: propolis in the form of ethanolic/hydroalcoholic extracts is "low toxicity" upon acute oral administration; with long-term use, reversible functional changes in the liver and kidneys are possible, as well as a high risk of skin sensitization in predisposed individuals. It is recommended to consider the solvent/carrier, sex-dependent differences in response, and individual allergological risks.

Pharmacodynamics — Propolis

The pharmacodynamic properties of propolis are due to a complex of biologically active substances, primarily polyphenols, flavonoids, aromatic acids, terpenoids, and essential oils. Experimental studies have established a pronounced antioxidant effect, manifested in the ability of propolis compounds to neutralize reactive oxygen and nitrogen species, inhibit lipid peroxidation, and stabilize cell membranes. This effect is realized at the systemic level in relation to various tissues and organs, including the nervous system, cardiovascular system, and skin.

Propolis possesses pronounced anti-inflammatory activity associated with the modulation of the synthesis of pro-inflammatory mediators, such as prostaglandins and cytokines. Studies have shown that propolis extracts can inhibit the activity of cyclooxygenases and lipoxygenases, reducing the production of pro-inflammatory factors. At the level of the immune system, regulation of the functional activity of T-lymphocytes, macrophages, and NK cells is observed, which manifests as immunostimulating and immunomodulatory effects. These effects are systemic in nature and are evident both with oral administration and with local application.

At the level of the nervous system, the ability of propolis compounds to exert a modulating effect on neurotransmitter processes, including the gamma-aminobutyric acid and catecholamine systems, has been experimentally confirmed. Several components demonstrate sedative and anxiolytic effects, likely related to an influence on CNS receptor complexes. This action is systemic and is predominantly expressed upon oral administration of extracts.

Regarding the cardiovascular system, propolis exhibits endothelioprotective and vasomodulatory effects, maintaining the elasticity of the vascular wall and reducing oxidative damage to the endothelium. Experimental data indicate the ability of compounds to reduce platelet aggregation, which is associated with the modulation of thromboxane and prostacyclin synthesis. This effect is realized mainly at the systemic level with internal use.

From the gastrointestinal tract, propolis is characterized by its ability to stimulate reparative processes of the mucous membrane and provide antioxidant protection to the epithelium. Studies have shown the activation of mucus synthesis, which helps increase the resistance of mucous membranes to damaging factors. These effects manifest mainly with oral administration of hydroalcoholic extracts.

At the level of the skin and mucous membranes, propolis exhibits local antimicrobial, antifungal, and regenerative action. This is due both to the direct antiseptic activity of the components and to the stimulation of keratinocyte and fibroblast proliferation. This property is actively used in the local application of ointments, creams, and infusions.

The totality of the pharmacodynamic effects of propolis allows it to be characterized as a multifunctional natural bioregulator, exerting antioxidant, anti-inflammatory, immunomodulatory, sedative, endothelioprotective, antimicrobial, and reparative effects at the systemic and local levels.

References:

— Burdock G.A. (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology, 36(4):347–363. (https://pubmed.ncbi.nlm.nih.go...)
— Sforcin J.M., Bankova V. (2011) Propolis: Is there a potential for the development of new drugs? Journal of Ethnopharmacology, 133(2):253–260. (https://pubmed.ncbi.nlm.nih.go...)
— Watanabe M.A.E., Amarante M.K., Conti B.J., Sforcin J.M. (2011) Cytotoxic constituents of propolis inducing anticancer effects: a review. Journal of Pharmacy and Pharmacology, 63(11):1378–1386. (https://pubmed.ncbi.nlm.nih.go...)

Pharmacokinetics — Propolis

The pharmacokinetic characteristics of propolis depend on the route of administration and the composition of the extract used. Upon oral administration, the active components — mainly polyphenols, flavonoids, and phenolic acids — undergo partial absorption in the gastrointestinal tract. The absorption rate depends on the solubility of the substance and interaction with the intestinal microflora, which can metabolize complex polyphenolic structures into simpler and more bioavailable compounds.

After absorption, a significant portion of the components undergoes primary metabolism in the liver with the formation of conjugates (glucuronides and sulfates), which determines further distribution in the body. Systemic circulation includes circulating metabolites that reach various tissues, including the liver, kidneys, lungs, skin, and mucous membranes.

With transdermal and local application in the form of ointments, creams, and oil infusions, propolis components provide a local concentration in the epidermis and dermis, where they exert antimicrobial and reparative effects. Systemic absorption through the skin is limited and insignificant.

When used on mucous membranes (oral cavity, nose, vagina, rectum), both local action and partial absorption of polyphenolic components are noted. This provides both a local antiseptic and regenerative effect, as well as a moderate systemic impact.

Propolis metabolism occurs primarily in the liver, involving enzyme systems responsible for the biotransformation of polyphenolic compounds. The intestinal microbiota plays an important role, participating in the breakdown of complex flavonoids. Excretion of metabolites occurs primarily in urine and bile. An insignificant portion of low-molecular-weight volatile compounds may be excreted through the lungs and skin.

Thus, the pharmacokinetics of propolis is determined by a multi-stage process: incomplete absorption in the gastrointestinal tract, metabolism in the liver and by intestinal microflora, distribution into tissues with pronounced tropism for target organs, and combined excretion via the kidneys, liver, and skin.

References:
— Piccinelli A.L., Lotti C., Campone L. et al. (2011) Chemical composition and antioxidant activity of propolis prepared in different solvents from honeybee hives of southern Italy. Food Chemistry, 125(2): 559–566. (https://pubmed.ncbi.nlm.nih.go...)
— Khalil M.L. (2006) Biological activity of bee propolis in health and disease. Asian Pacific Journal of Cancer Prevention, 7(1):22–31. (https://pubmed.ncbi.nlm.nih.go...)
— Watanabe M.A.E., Amarante M.K., Conti B.J., Sforcin J.M. (2011) Cytotoxic constituents of propolis inducing anticancer effects: a review. Journal of Pharmacy and Pharmacology, 63(11):1378–1386. (https://pubmed.ncbi.nlm.nih.go...)

Mechanisms of Action and Scientific Rationale — Propolis

The complex of active substances in propolis realizes its effects through diverse molecular and cellular mechanisms. Polyphenolic compounds, particularly flavonoids and phenolic acids, exhibit the ability to inhibit the enzymes cyclooxygenases (COX-1 and COX-2) and lipoxygenases (LOX), leading to a reduction in the synthesis of prostaglandins and leukotrienes. This is accompanied by modulation of inflammatory processes at the level of target cells, including macrophages and neutrophils. Simultaneously, the blocking of NF-κB activation, a key signaling cascade of the inflammatory response, is observed, which further reduces the transcription of pro-inflammatory cytokines.

On the other hand, propolis can activate antioxidant pathways associated with increased expression of the enzymes superoxide dismutase, catalase, and glutathione peroxidase. These mechanisms help protect endothelial cells from oxidative stress, stabilize cell membranes, and reduce damage to lipid structures. Propolis polyphenols demonstrate the ability to scavenge reactive oxygen and nitrogen species, which provides a systemic antioxidant effect.

The influence on the immune system is manifested through the regulation of T-lymphocyte and NK cell activity, as well as the modulation of cytokine production, such as interleukins and tumor necrosis factor. Studies have shown that propolis compounds can alter the balance between the Th1 and Th2 response, and also stimulate the phagocytic activity of macrophages. These effects are partly related to the modulation of the JAK/STAT signaling pathway and an influence on the expression of genes controlling the immune response.

Certain flavonoid components and terpenoids of propolis can interact with central nervous system receptors, including GABA_A receptors and serotonin receptors. This action manifests in reduced neuronal excitability, an effect on dopaminergic and serotonergic cascades, and the potential for sedative and anxiolytic effects. The influence on neurotransmitter systems is complemented by the modulation of calcium channels and an effect on the MAPK cascade, which provides neuroprotective properties.

Furthermore, propolis exhibits pronounced antimicrobial activity associated with the destruction of bacterial membranes, disruption of nucleic acid synthesis, and inhibition of enzymes involved in microbial metabolism. This effect is noted against both gram-positive and gram-negative bacteria, as well as fungi. An important mechanism is considered to be the ability of individual phenolic compounds to bind to membrane proteins of microorganisms, altering their permeability and viability.

References:
— Sforcin J.M., Bankova V. (2011) Propolis: Is there a potential for the development of new drugs? Journal of Ethnopharmacology, 133(2):253–260. (https://pubmed.ncbi.nlm.nih.go...)
— Watanabe M.A.E., Amarante M.K., Conti B.J., Sforcin J.M. (2011) Cytotoxic constituents of propolis inducing anticancer effects: a review. Journal of Pharmacy and Pharmacology, 63(11):1378–1386. (https://pubmed.ncbi.nlm.nih.go...)
— Burdock G.A. (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology, 36(4):347–363. (https://pubmed.ncbi.nlm.nih.go...)

Synergy — Propolis

Synergistic effects of propolis have been confirmed in combination with various medicinal plants and natural compounds. Several studies have shown that the combined use of propolis and Camellia sinensis (green tea) leads to a potentiation of the antioxidant effect due to the mutual enhancement of the activity of catechins and propolis flavonoids. This effect is realized through the additive inhibition of lipid peroxidation and the enhancement of antioxidant enzyme activity.

In the combination of propolis and Echinacea purpurea, a modulating effect on the immune system is noted, expressed in increased cytokine production and macrophage activation. This result is explained by the cumulative effect of propolis phenolic compounds and echinacea alkylamides on the JAK/STAT and NF-κB signaling pathways, leading to a potentiation of immunomodulatory effects.

The combined use of propolis and Curcuma longa (turmeric) demonstrates a potentiating anti-inflammatory effect. In vitro studies indicate additive inhibition of COX-2 and NF-κB, as well as a reduction in the production of pro-inflammatory cytokines. This combination is considered an example of synergy between phenolic and curcuminoid compounds acting on the same enzyme targets.

The interaction of propolis with vitamin C exhibits a protective and potentiating antioxidant effect. A combined enhancement of ascorbate regeneration and an increase in the level of endogenous antioxidant enzymes are observed. This type of interaction is tissue-specific, being particularly pronounced in endothelial and epithelial cells.

Additional studies have shown synergy between propolis and Glycyrrhiza glabra (licorice), where an additive antimicrobial effect was noted. The combination of propolis phenolic acids and licorice saponins leads to the disruption of bacterial membrane integrity and an enhancement of the antibacterial potential.

References:
— Paulino N. et al. (2003) Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle. Journal of Ethnopharmacology, 88(2-3):189–196. (https://pubmed.ncbi.nlm.nih.go...)
— Sforcin J.M. (2007) Propolis and the immune system: a review. Journal of Ethnopharmacology, 113(1):1–14. (https://pubmed.ncbi.nlm.nih.go...)
— Araujo M.J.A.M. et al. (2020) Propolis and curcumin: a synergistic association. Phytomedicine, 68:153173. (https://pubmed.ncbi.nlm.nih.go...)
— Fischer G. et al. (2007) Synergistic effect of propolis with antibiotics against Salmonella enterica. Journal of Applied Microbiology, 103(5):1744–1753. (https://pubmed.ncbi.nlm.nih.go...)

Geography of Use and Traditional Medicine — Propolis

Propolis has been known as a traditional remedy in the cultures of virtually all regions where beekeeping developed. Its use can be traced back to antiquity: in Egypt, propolis was used by priests for embalming bodies and was considered a substance of cleansing power; ancient sources mention the use of bee glue in the medical practice of the Greeks and Romans for wound care and preserving tissue integrity. In the Slavic herbalist tradition, it was used in the form of infusions and applications to strengthen the body and was considered a natural protective agent. In Medieval Europe, monastic herbals included propolis in remedies for skin care and respiratory health, and it was also used in ritual practice as a substance with cleansing action.

In traditional Chinese medicine, propolis appeared later but was perceived as a substance that strengthens vital energy and harmonizes the body's internal processes. In Japan, it was known within folk apitherapy, where it was used to maintain strength and vitality. In the Tibetan tradition, mentions of propolis are found in 17th-century manuscripts, where it was considered a natural remedy supporting the balance of bodily energies.

In South and Southeast Asia, propolis was used in the Indian system of Ayurveda, where it was considered a cleansing substance that supports the balance of the doshas. In Thai folk medicine, bee glue was used as a component of decoctions and infusions, as well as in ritual practices to protect the home from evil spirits. In the cultures of Central Asia and the Caucasus, propolis was used in the form of incense and amulets, as well as as part of economic and domestic traditions associated with beekeeping.

Among the peoples of Latin America, propolis was traditionally used as a natural remedy for body care and in shamanic practices for space cleansing. In the culture of the indigenous tribes of Brazil and Peru, it was considered a gift from the bees, providing spiritual strength and protection. In African ethnographic data, propolis is mentioned as a substance used for ritual purposes, including purification ceremonies.

Thus, the geography of propolis use covers Europe, Asia, Africa, and America. It has been used both for medical purposes (infusions, decoctions, wraps, applications, fumigation) and in cult-magical practices. Its status as a "bee gift" unites many traditions where it was perceived not only as a medicinal but also as a sacred substance, endowed with protective and cleansing power.