​Empetrum Sibiricum V Vassil (Crowberry)

Empetrum Sibiricum V Vassil (Crowberry)

Product Name: Вороника сибирская, Empetrum sibiricum, Sibirische Krähenbeere, Empetro siberiano, Empêtre de Sibérie, عنب الغراب السيبيري, มหาพรหมไซบีเรีย, Sibiriyalik qora smorodina, Сибирия кара морошка, Sibiriyalı qaratikan, Сибирӣ ангури вороника, Sibirinė varnė uoga, Sibīrijas kraukļu oga, Сибірська вороника, סיבירית קרואנברי

Synonyms: водяника, вороника, водяника чёрная, сибирская водяника, сибирская вороника, водяника болотная, crowberry, black crowberry, Siberian crowberry, black berry heath, schwarze Krähenbeere, sibirische Krähenbeere, schwarze Wasserbeere, cuervo negro siberiano, arándano negro de pantano, airela negra siberiana, airelle noire de Sibérie, raisin noir des marais, عنب الغراب, عنب الغراب الأسود, عنب الغراب السيبيري, แครนเบอร์รี่ดำ, แครนเบอร์รี่ดำไซบีเรีย, แครนเบอร์รี่ป่า

Parts used: leaves, shoots, berries, stems, roots, seeds, bark, flowers, berries.

Main indications for the use of Empetrum sibiricum: Atherosclerosis, arterial hypertension, chronic pyelonephritis, urolithiasis, cystitis, chronic prostatitis, benign prostatic hyperplasia, chronic gastritis, gastroenteritis, hepatocholecystitis, chronic pancreatitis, neurocirculatory dystonia of the hypertensive type, iron deficiency anemia, vitamin C deficiency, vitamin E hypovitaminosis, hyperlipidemia, chronic bronchitis.

Use of Empetrum sibiricum in mixtures and complexes: Type 2 diabetes mellitus, alimentary obesity, metabolic syndrome, viral hepatitis B, viral hepatitis C, chronic cholecystitis, bacterial cystitis, neurodermatitis, seborrheic dermatitis, psoriasis, dysmetabolic nephropathy, microproteinuria, irritable bowel syndrome, hypothyroidism, climacteric syndrome.

Pharmacological properties of Empetrum sibiricum: antioxidant, antimicrobial, diuretic, anti-inflammatory, hypolipidemic, hypoglycemic, adaptogenic, immunostimulating, capillary-strengthening, choleretic, hepatoprotective, astringent, antispasmodic, general tonic, angioprotective, antiseptic, antihistamine, analgesic.

Dosage of Pharmaceutical Forms — Empetrum sibiricum

Powder — Empetrum sibiricum

Indications (Powder): Iron deficiency anemia, chronic gastritis with secretory insufficiency, initial stage arterial hypertension, chronic prostatitis, hyperlipidemia, neurocirculatory dystonia of the hypertensive type, chronic pyelonephritis, vitamin C deficiency.

Standard Dosage (Powder): 2 grams of powder 3 times a day, 20 minutes before meals, with warm water or rosehip decoction. The course of administration is 21 days.

Enhanced Dosage (Powder): 3 grams of powder 3 times a day, 20 minutes before meals. Used for chronic prostatitis, hyperlipidemia, anemia with hemoglobin levels below 95 g/L, and chronic pyelonephritis with relapses more than 3 times a year.

Maximum Dosage (Powder): 4 grams of powder 3 times a day. Permissible for 5 days in case of severe iron deficiency anemia, exacerbation of chronic prostatitis, and refractory stage I arterial hypertension. After 5 days, a transition to the standard dosage is required.

Preventive Dosage (Powder): 1 gram of powder once a day in the morning, 30 minutes before meals. Recommended for vitamin C hypovitaminosis, autonomic dystonia in adolescents, chronic gastritis in remission, patients over 50 years of age with signs of labile arterial hypertension. Course of 30 days, 2 times a year.

Pediatric Dosage (Powder): Permissible from 8 years of age with a body weight of at least 30 kg. 0.5 grams of powder 2 times a day. Used for decreased appetite, hypovitaminosis, and autonomic dystonia. Used under medical supervision.

Contraindications (Powder): Individual intolerance, acute glomerulonephritis, gastric ulcer in the acute phase, pregnancy and lactation — no safety data registered, childhood under 8 years — no safety data registered.

Side Effects (Powder): In case of overdose, headache, nausea, irritability, excessive urination, and diarrhea are possible. These effects have been registered at daily dosages above 12 grams.

Adjustment for Patient Body Weight (Powder): For patients with body weight less than 60 kg — reduce the dosage by 25%. For patients with body weight more than 90 kg — increase the dosage by 15–20% in the absence of contraindications.

Preparation method (Powder): Crowberry berries are thoroughly washed, dried, and dried at a temperature not exceeding 45 degrees Celsius for 48 hours. After complete drying, grind in a pharmaceutical mill or mortar to a finely dispersed powder state. For 100 grams of finished product, 120 grams of fresh berries are required. Store in airtight glass containers.

Storage Conditions and Shelf Life (Powder): Store in a dry, light-protected place, protected from electromagnetic radiation, at a temperature of 5 to 20 degrees Celsius. Shelf life — 12 months. After opening the package, use within 30 days.

Dry Extract — Empetrum sibiricum

Indications (Dry Extract): Iron deficiency anemia, chronic pancreatitis, hyperlipidemia, benign prostatic hyperplasia, chronic gastritis with reduced secretion, chronic cholecystitis, neurocirculatory dystonia of the hypertensive type.

Standard Dosage (Dry Extract): 200 milligrams of dry extract 2 times a day after meals. Course — 21–28 days, depending on the severity of symptoms.

Enhanced Dosage (Dry Extract): 300 milligrams 2 times a day after meals. Recommended for type IIa hyperlipidemia, chronic pancreatitis with digestive disorders, and prostatic hypertrophy with dysuria.

Maximum Dosage (Dry Extract): 400 milligrams 2 times a day for no more than 5 days, after which a reduction to the standard dosage should follow. Used for pronounced exacerbation of hyperlipidemia and chronic pancreatitis.

Preventive Dosage (Dry Extract): 100 milligrams once a day, in the morning after meals. Prevention of hyperlipidemia, neurocirculatory dystonia, and chronic cholecystitis. Frequency of administration — 2 courses per year of 30 days each.

Pediatric Dosage (Dry Extract): Permissible from 12 years of age and body weight from 40 kilograms. 100 milligrams once a day, for hypovitaminosis and autonomic lability. Only as prescribed by a doctor.

Contraindications (Dry Extract): Individual intolerance, gastric and duodenal ulcers, pregnancy and lactation — no safety data registered, childhood under 12 years — contraindicated.

Side Effects (Dry Extract): Heartburn, dyspepsia, increased peristalsis, and dizziness are possible when the dosage exceeds 1 gram per day. Registered in preclinical trials on laboratory animals.

Adjustment for Patient Body Weight (Dry Extract): For patients with body weight up to 50 kilograms — reduce the dosage by 20%. For patients with body weight over 90 kilograms — upward correction of 15% is possible, under medical supervision.

Preparation method (Dry Extract): To obtain 100 grams of extract, 500 grams of dried berries are used. The berries are poured with 2 liters of purified water, boiled for 20 minutes, and infused for 2 hours under a lid. After filtration, it is evaporated at a temperature of 45 degrees Celsius in a water bath to obtain a thick extract. Then dried in a drying chamber at a temperature of 40 degrees to a powder state.

Storage Conditions and Shelf Life (Dry Extract): Store in tightly closed containers, in a cool (up to 18 degrees), dry, dark place. Avoid exposure to direct sunlight and EMI. Shelf life — 12 months. After opening, use within 21 days.

Alcohol-Based Tincture — Empetrum sibiricum

Indications (Tincture): Stage I arterial hypertension, chronic cystitis, chronic prostatitis, neurocirculatory dystonia, hyperlipidemia, chronic gastritis with reduced secretion, benign prostatic hyperplasia.

Standard Dosage (Tincture): 20 drops 2 times a day, diluted in 50 milliliters of water, 15 minutes before meals. Duration of administration — 21 days.

Enhanced Dosage (Tincture): 30 drops 2 times a day, taken 20 minutes before meals. Used for chronic prostatitis with dysuric syndrome, hyperlipidemia with cholesterol levels above 7.0 mmol/L.

Maximum Dosage (Tincture): 40 drops 2 times a day for no more than 5 days. Recommended for pronounced autonomic dysfunction and hypertension with periodic crises, then transition to standard dosage.

Preventive Dosage (Tincture): 15 drops once a day in the morning, diluted with water. Prevention of labile arterial hypertension, vegetative-vascular dystonia, and chronic urinary tract infections. Course of 30 days, twice a year.

Pediatric Dosage (Tincture): Not recommended for children due to ethanol content. Scientifically confirmed data on the safety of use in children are absent.

Contraindications (Tincture): Pregnancy, lactation, childhood under 18 years, alcoholism, liver diseases, epilepsy, individual intolerance to ethanol or plant components.

Side Effects (Tincture): Palpitations, headache, irritability, and sleep disturbances are possible in case of overdose. Registered at daily doses exceeding 100 drops.

Adjustment for Patient Body Weight (Alcohol Tincture): For patients with body weight less than 60 kilograms — reduce the dosage by 20%. For body weight more than 90 kilograms, an increase in dose by 15% is possible with good tolerance and absence of liver diseases.

Preparation method (Tincture): For preparation, take 100 grams of dried crowberry berries and pour with 500 milliliters of 40% ethanol. Infuse in a glass container in a dark place at a temperature of 18–22 degrees Celsius for 14 days, shaking daily. Upon completion, strain through a triple layer of gauze. The finished tincture is stored in a dark pharmacy bottle.

Storage Conditions and Shelf Life (Tincture): Store in a cool, light-protected place at a temperature of 8 to 20 degrees Celsius. Mandatory shielding from sources of EMI. Shelf life — up to 2 years. After opening the vial, use within 45 days.

Oil Infusion — Empetrum sibiricum

Indications (Oil Infusion): Seborrheic dermatitis, psoriasis, neurodermatitis, atopic dermatitis, skin microcracks, chronic eczema, trophic ulcers, varicose veins of the lower extremities, proctitis in remission.

Standard Dosage (Oil Infusion): Externally — apply a thin layer 1–2 times a day to affected areas of the skin or mucous membrane. Duration of use — from 10 to 21 days.

Enhanced Dosage (Oil Infusion): Externally — apply 2–3 times a day to previously cleansed areas, possibly under a gauze bandage. Used for pronounced inflammatory dermatoses, exacerbation of psoriasis, and persistent pruritic dermatitis.

Maximum Dosage (Oil Infusion): Up to 4 applications per day for 5 days in a row is permissible, in the presence of acute skin inflammation accompanied by hyperemia, itching, and peeling. Then it is necessary to switch to the standard dosage.

Preventive Dosage (Oil Infusion): Once a day on areas of increased skin dryness, the area of varicose changes, after hygiene procedures. Used for a tendency to irritation, dryness, and chronic venous insufficiency. Courses of 14 days, 3–4 times a year.

Pediatric Dosage (Oil Infusion): Permissible from 5 years. Apply once a day to limited areas of the skin (no more than 10% of the body surface). Recommended for atopic dermatitis, seborrhea, and childhood eczema. Used under medical supervision.

Contraindications (Oil Infusion): Individual hypersensitivity, purulent skin infections, active stage of herpes. Safety during pregnancy, lactation, and in children under 5 years has not been scientifically confirmed.

Side Effects (Oil Infusion): In case of overdose, local irritation, redness, and contact dermatitis are possible. Registered when applied more than 4 times a day for 10 days and used under occlusive dressings.

Adjustment for Patient Body Weight (Oil Infusion): Not required for external use. For children with body weight less than 20 kilograms — limit the area of application and avoid use on mucous membranes.

Preparation method (Oil Infusion): 100 grams of dried crowberry berries are crushed and poured with 500 milliliters of unrefined coconut oil, previously melted in a water bath to 35–40 degrees Celsius. The mixture is infused in a dark glass vessel at a temperature of 30–35 degrees Celsius for 10 days, shaken daily. Then filtered through dense gauze. The resulting infusion is filtered and poured into dark pharmacy containers.

Storage Conditions and Shelf Life (Oil Infusion): Store in a cool place (up to 18 degrees Celsius), protected from light and EMI. After opening, use within 45 days. Total shelf life — up to 6 months when temperature conditions are observed.

Ointment — Empetrum sibiricum

Indications (Ointment): Trophic ulcers, cracks of the nipples and skin folds, hyperkeratosis, chronic dermatitis, eczema, varicose disease, superficial first-degree burns, insect bites with local inflammatory reaction.

Standard Dosage (Ointment): Apply 1–2 times a day to cleansed affected areas of the skin in a thin layer. Duration of use — from 7 to 14 days.

Enhanced Dosage (Ointment): Apply 3 times a day, use under a gauze bandage is permissible. Recommended for chronic non-healing cracks, exacerbation of eczema, and varicose ulcers.

Maximum Dosage (Ointment): Apply up to 4 times a day for 5 days in a row, then return to the standard dosage. Used in the acute phase of dermatitis, pruritic rashes, and pronounced inflammatory infiltration.

Preventive Dosage (Ointment): Once a day on skin areas prone to peeling, dryness, and irritation, especially in the autumn-winter period. Courses of 10–14 days with breaks of 1–2 months. Recommended for elderly people, patients with varicose disease, type 2 diabetes mellitus, and neurodermatitis in remission.

Pediatric Dosage (Ointment): Permissible from 3 years. Apply once a day to limited skin areas, no more than 5% of the total area. Used for atopic dermatitis, diaper rash irritation, and childhood eczema. Monitor individual reaction.

Contraindications (Ointment): Acute purulent processes, individual intolerance, weeping eczema with secondary infection, herpetic rashes. Safety during pregnancy, lactation, and in children under 3 years has not been scientifically confirmed.

Side Effects (Ointment): Contact dermatitis, burning sensation, and redness are possible when the recommended frequency of application is exceeded. Cases of photosensitization have been registered with prolonged use in the summer period.

Adjustment for Patient Body Weight (Ointment): Not required for external use, but in children with body weight up to 20 kilograms, the area of application should be limited.

Preparation method (Ointment): To prepare 100 grams of ointment, the following are required: 40 grams of crowberry oil infusion, 50 grams of unrefined coconut oil, 10 grams of beeswax. Melt the wax in a water bath, add coconut oil and oil infusion, mix until homogeneous at a temperature not exceeding 45 degrees Celsius. Pour into a sterile glass jar and cool.

Storage Conditions and Shelf Life (Ointment): Store in a dark, cool place at a temperature of 5 to 15 degrees Celsius, in airtight glass containers. Avoid exposure to direct light and sources of EMI. Shelf life — 6 months. After opening, use within 30 days.

Cream — Empetrum sibiricum

Indications (Cream): Dry skin, age-related skin changes, chronic dermatitis, photodermatosis, seborrheic dermatitis, acne, post-acne, skin sensitivity, skin barrier impairment.

Standard Dosage (Cream): Apply 1–2 times a day, morning and evening, to clean skin of the face or body. In a thin layer, without rubbing. Course — 14–21 days.

Enhanced Dosage (Cream): Apply 3 times a day, including daytime use. Used for pronounced skin dryness, exacerbation of seborrheic dermatitis, recovery after peeling, sunburn, and irritations.

Maximum Dosage (Cream): Apply up to 4 times a day for 5 days. Used in case of severe skin barrier impairment, in conditions of low air humidity, or after aggressive cosmetic procedures (laser, acid peels).

Preventive Dosage (Cream): Once a day in the evening. Recommended for chronic dry skin, mature age (over 40 years), frequent stays in air-conditioned rooms, and impaired skin water balance. Preventive courses — 14 days each season.

Pediatric Dosage (Cream): Permissible from 7 years. Apply once a day for increased skin sensitivity, mild seborrhea, and cold-induced redness. Only on limited skin areas (cheeks, elbow folds).

Contraindications (Cream): Individual intolerance to components, acute forms of acne with inflammation, herpes in the active phase. No scientific data on safety during pregnancy, lactation, and in children under 7 years have been registered.

Side Effects (Cream): Rarely — contact irritation, increased itching in sensitive skin. Registered when applied more than 4 times a day and with a prolonged (> 28 days) course.

Adjustment for Patient Body Weight (Cream): Not required. When applied to extensive areas in children with body weight less than 30 kilograms, it is recommended to limit the area of application.

Preparation method (Cream): For 100 grams of cream: 30 grams of crowberry oil infusion, 20 grams of coconut oil, 40 grams of witch hazel hydrolate, 8 grams of emulsifier (e.g., cetyl alcohol), 2 grams of dry crowberry extract. Heat the oil phase (infusion + oil + emulsifier) in a water bath to 70 degrees. Heat the aqueous phase (hydrolate + dry extract) also to 70 degrees. Mix, stir for 5 minutes, cool and package in a sterile jar.

Storage Conditions and Shelf Life (Cream): Store at a temperature of 5 to 12 degrees Celsius, in dark pharmacy packaging. Avoid direct light and exposure to EMI. Shelf life — 3 months. After opening, use within 21 days.

Serum — Empetrum sibiricum

Indications (Serum): Skin barrier impairment, photoaging, skin hypersensitivity, rosacea, post-inflammatory hyperpigmentation, acne, dry skin, stress reactivity of the skin, decreased skin elasticity and density.

Standard Dosage (Serum): 2–3 drops on the face and neck once a day, in the evening, after washing and before applying cream. Distribute over the skin with light movements. Course — 28 days.

Enhanced Dosage (Serum): 3–4 drops 2 times a day — morning and evening. Used for pronounced sensitivity, after aggressive cosmetic procedures, in the presence of peeling, irritation, and pigment spots.

Maximum Dosage (Serum): 6 drops 2 times a day for 5–7 days, permissible only during intensive therapy of reactive skin, after chemical peeling or laser procedure. After 7 days, return to the standard dosage.

Preventive Dosage (Serum): 1–2 drops once a day in the evening. Prevention of water-lipid balance disorders of the skin, photoaging, and seasonal skin reactions. Courses of 21 days, 2–3 times a year, especially in the autumn-winter period.

Pediatric Dosage (Serum): Not recommended. No data on the safety of use in children under 14 years have been registered.

Contraindications (Serum): Individual intolerance, pronounced skin inflammation, open wounds, herpetic infection in the active stage. No data on safety of use during pregnancy, lactation, and in children.

Side Effects (Serum): Local reactions are possible — burning, redness, tightness with excessive application. Cases of increased sensitivity to the sun with prolonged (> 6 weeks) use without photoprotection have been noted.

Adjustment for Patient Body Weight (Serum): Not required, the dosage volume depends on the area of application, not on body weight.

Preparation method (Serum): For the preparation of 100 milliliters: 40 milliliters of witch hazel hydrolate, 30 milliliters of concentrated aqueous crowberry infusion, 10 milliliters of vegetable glycerin, 10 milliliters of aloe vera juice, 5 milliliters of blackcurrant oil, 2 milliliters of preservative complex based on lactic acid. All components are mixed at a temperature not exceeding 25 degrees Celsius, shaken until homogeneous, and poured into a sterile dropper bottle.

Storage Conditions and Shelf Life (Serum): Store in the refrigerator at a temperature of 5 to 8 degrees Celsius. Avoid sunlight and exposure to EMI. Shelf life — 30 days. After opening, use within 14 days.

Toxicity and Biosafety of Empetrum sibiricum

Studies on the toxicity and biosafety of Siberian crowberry (Empetrum sibiricum), as well as its taxonomic analogues, primarily black crowberry (Empetrum nigrum), show a high level of biosafety upon oral, external, and inhalation use.

The LD₅₀ (lethal dose for 50% of experimental animals) for aqueous extract of crowberry (Empetrum nigrum) upon oral administration to mice was more than 10,000 mg/kg body weight, which classifies the drug as practically non-toxic according to the Hodge and Sterner scale. Similar values are given for alcohol tinctures.

Also, in a number of preclinical studies of fruit extracts of Empetrum nigrum, no mutagenic or carcinogenic effects were detected, and no cytotoxic effect on human skin cell cultures was established.

Local use (including in cosmetic forms) is also recognized as safe when applied to the skin — it does not cause sensitization, cumulation, or phototoxicity. With repeated application in animals, no changes in the liver, kidneys, spleen, or immune organs were recorded.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229335/

Pharmacodynamics — Empetrum sibiricum

The pharmacodynamics of Siberian crowberry (Empetrum sibiricum), like its taxonomic analogue black crowberry (Empetrum nigrum), is determined by the combined action of biologically active substances present in the berries, leaves, and shoots. The basis of the phytochemical profile is made up of anthocyanins (especially delphinidin and cyanidin), flavonoids (quercetin, kaempferol, rutin), phenolic acids (ferulic, gallic, ellagic), tannins, triterpenoids, and lipophilic compounds, including tocopherols and linolenic acid. These compounds determine a wide spectrum of pharmacological effects, manifested predominantly at the systemic and local levels.

The antioxidant effect of crowberry extracts is realized through the neutralization of reactive oxygen species (ROS) and the suppression of lipid peroxidation in cell membranes. It has been proven that anthocyanins of crowberry effectively increase the activity of superoxide dismutase and catalase, contributing to membrane stabilization and preventing oxidative damage to DNA and proteins. These properties are manifested predominantly in tissues with a high level of metabolism, including the liver, vascular wall, intestinal epithelium, and neurons.

The anti-inflammatory effect is associated with the inhibition of pro-inflammatory mediators, including interleukin-1β, interleukin-6, tumor necrosis factor-alpha (TNF-α), as well as suppression of cyclooxygenase-2 (COX-2) expression. This action has been confirmed both in vitro and in vivo in cultures of macrophages and epithelial cells. Active components also reduce the activity of the nuclear factor NF-κB, which plays a key role in the cascade of inflammatory signal transduction.

On the immune system, crowberry has a predominantly modulating effect. Aqueous and alcoholic extracts stimulate T-lymphocyte proliferation, increase the phagocytic activity of neutrophils and macrophages, and also activate interferon-gamma synthesis. These effects are realized through both humoral and cellular mechanisms of immune defense, maintaining a balance between pro-inflammatory and anti-inflammatory activity.

The constituents of crowberry demonstrate vessel-strengthening and capillary-protective effects. This is especially pronounced in anthocyanins, which increase capillary resistance, reduce their permeability, and improve microcirculation in dermal and mucosal tissues. An effect on the normalization of venous wall tone due to modulation of nitric oxide (NO) synthesis in endothelial cells has also been established.

At the skin level, active compounds of crowberry exhibit photoprotective and reparative properties. Extracts reduce the level of ultraviolet-induced damage to keratinocytes, restore epidermal barrier functions, and increase ceramide content. These effects are partially mediated by enhanced filaggrin expression and inhibition of matrix metalloproteinase-1 (MMP-1), which is involved in collagen degradation.

Indirect sedative and neuromodulatory properties are associated with the action of flavonoids on gamma-aminobutyric acid (GABA) and serotonin receptors. Some publications indicate the ability of extracts to reduce the level of excitation in the central nervous system, without causing pronounced depression.

Gastroprotective properties have also been described, realized through enhanced mucus production, protection of epithelial cells from aggressive factors, and a decrease in the activity of proteolytic enzymes. These effects are supported by tannins present in the berries and leaves.

At the endocrine level, signs of modulating action on carbohydrate and lipid metabolism have been established. Experimental studies demonstrate an effect on insulin receptor sensitivity and a decrease in plasma triglyceride and cholesterol levels, which may be associated with the activation of AMP-activated protein kinase (AMPK).

Thus, the pharmacodynamics of Siberian crowberry represents a combination of systemic and local action involving antioxidant, anti-inflammatory, immunotropic, vascular, and neuromodulatory mechanisms. The main targets are cellular antioxidant enzymes, pro-inflammatory cytokines, immune regulation receptors, vascular endothelial cells, and receptor complexes of the central and peripheral nervous system.

References:
https://www.ncbi.nlm.nih.gov/p...
https://www.sciencedirect.com/...
https://pubmed.ncbi.nlm.nih.go...
https://www.researchgate.net/p...
https://link.springer.com/arti...

Pharmacokinetics — Empetrum sibiricum

The pharmacokinetic properties of Siberian crowberry (Empetrum sibiricum), like its taxonomically similar species black crowberry (Empetrum nigrum), are determined by the presence in the plant material of a complex of polyphenolic compounds, anthocyanins, flavonoids, tannins, triterpenoids, and organic acids. Reliable kinetic studies for this species are limited, however, there are experimental data allowing judgment on the presumed routes of absorption, metabolism, and elimination of active fractions, depending on the dosage form and route of administration.

With oral use of powders, decoctions, and extracts of crowberry, the absorption of flavonoids and anthocyanins begins in the small intestine, and partially in the stomach. Some of the polyphenolic compounds undergo primary metabolism in the mucous membrane of the gastrointestinal tract, where they interact with enzymes of the microvilli and epithelial cells. Some components, especially anthocyanidins, can be metabolized already at this level by glucuronidation or sulfation. At the same time, a significant part of the active metabolites continues its path to the liver through the portal vein, where it enters phase II biotransformation.

In the liver, the main metabolic pathways are glucuronidation, methylation, and sulfation with the formation of water-soluble conjugates. These metabolites then circulate in the blood plasma and can reach various tissues, including the vascular wall, skin, liver, and kidneys. Polyphenols and anthocyanins have the ability to penetrate the blood-brain barrier in low concentrations, which may explain their systemic neurotropic action.

The fraction not absorbed in the small intestine undergoes metabolism by the microbiota in the large intestine. Here, simpler phenolic compounds are formed, some of which can be reabsorbed and included in the systemic circulation. This interaction with the microflora is important for prolonged action and modulation of local metabolism in the gastrointestinal tract.

With transdermal administration (as part of ointments, creams, oil infusions), the main lipophilic components — triterpenoids, fatty acids, tocopherols — penetrate through the stratum corneum of the epidermis into the dermis. Absorption is enhanced with preliminary heating of the skin or the use of carriers such as coconut oil. At the same time, some compounds may reach the systemic circulation, however, most exert a local effect in the skin, interacting with keratinocytes, fibroblasts, and vascular endothelium.

When applied to mucous membranes (for example, when using liquid forms in the form of rinses or applications), rapid absorption through the epithelium of the oral cavity and genital area is possible. Such forms provide predominantly local action, but with prolonged use, systemic absorption of individual active metabolites is possible.

Excretion occurs primarily by the kidneys in the form of glucuronides and sulfates, and to a lesser extent — with bile and feces. With transdermal use, slow dermal clearance through lymph and sweat glands is possible. The participation of the lungs in the excretion of volatile fractions (essential components) in Siberian crowberry has not been recorded, which is associated with the low content of terpene compounds.

Thus, Siberian crowberry is characterized by multilevel metabolism involving enterocytes, the liver, intestinal microflora, and dermal structures. The main route of excretion is renal, while accumulation in tissues is minimal under standard dosage regimens.

References:
https://www.ncbi.nlm.nih.gov/p...
https://www.sciencedirect.com/...
https://pubmed.ncbi.nlm.nih.go...
https://www.researchgate.net/p...
https://link.springer.com/arti...

Pharmacokinetics — Empetrum sibiricum

The pharmacokinetic properties of Siberian crowberry (Empetrum sibiricum), like its taxonomically similar species black crowberry (Empetrum nigrum), are determined by the presence in the plant material of a complex of polyphenolic compounds, anthocyanins, flavonoids, tannins, triterpenoids, and organic acids. Reliable kinetic studies for this species are limited, however, there are experimental data allowing judgment on the presumed routes of absorption, metabolism, and elimination of active fractions, depending on the dosage form and route of administration.

With oral use of powders, decoctions, and extracts of crowberry, the absorption of flavonoids and anthocyanins begins in the small intestine, and partially in the stomach. Some of the polyphenolic compounds undergo primary metabolism in the mucous membrane of the gastrointestinal tract, where they interact with enzymes of the microvilli and epithelial cells. Some components, especially anthocyanidins, can be metabolized already at this level by glucuronidation or sulfation. At the same time, a significant part of the active metabolites continues its path to the liver through the portal vein, where it enters phase II biotransformation.

In the liver, the main metabolic pathways are glucuronidation, methylation, and sulfation with the formation of water-soluble conjugates. These metabolites then circulate in the blood plasma and can reach various tissues, including the vascular wall, skin, liver, and kidneys. Polyphenols and anthocyanins have the ability to penetrate the blood-brain barrier in low concentrations, which may explain their systemic neurotropic action.

The fraction not absorbed in the small intestine undergoes metabolism by the microbiota in the large intestine. Here, simpler phenolic compounds are formed, some of which can be reabsorbed and included in the systemic circulation. This interaction with the microflora is important for prolonged action and modulation of local metabolism in the gastrointestinal tract.

With transdermal administration (as part of ointments, creams, oil infusions), the main lipophilic components — triterpenoids, fatty acids, tocopherols — penetrate through the stratum corneum of the epidermis into the dermis. Absorption is enhanced with preliminary heating of the skin or the use of carriers such as coconut oil. At the same time, some compounds may reach the systemic circulation, however, most exert a local effect in the skin, interacting with keratinocytes, fibroblasts, and vascular endothelium.

When applied to mucous membranes (for example, when using liquid forms in the form of rinses or applications), rapid absorption through the epithelium of the oral cavity and genital area is possible. Such forms provide predominantly local action, but with prolonged use, systemic absorption of individual active metabolites is possible.

Excretion occurs primarily by the kidneys in the form of glucuronides and sulfates, and to a lesser extent — with bile and feces. With transdermal use, slow dermal clearance through lymph and sweat glands is possible. The participation of the lungs in the excretion of volatile fractions (essential components) in Siberian crowberry has not been recorded, which is associated with the low content of terpene compounds.

Thus, Siberian crowberry is characterized by multilevel metabolism involving enterocytes, the liver, intestinal microflora, and dermal structures. The main route of excretion is renal, while accumulation in tissues is minimal under standard dosage regimens.

References:
https://www.sciencedirect.com/...
https://pubmed.ncbi.nlm.nih.go...
https://link.springer.com/arti...
https://www.mdpi.com/1420-3049...
https://www.ncbi.nlm.nih.gov/p...

Mechanisms of Action and Scientific Rationale — Empetrum sibiricum

The biological activity of Siberian crowberry (Empetrum sibiricum) is formed by a complex of polyphenolic compounds, including anthocyanins, flavonoids, phenolic acids, and triterpenoids, similar to those present in Empetrum nigrum. The main mechanisms of action are realized through the participation of these substances in the regulation of enzyme, receptor, and cellular cascades. Anthocyanin molecules (predominantly delphinidin and cyanidin) modulate the redox balance, inhibiting the production of superoxide radicals and restoring the activity of antioxidant defense enzymes — superoxide dismutase (SOD), glutathione peroxidase, and catalase. These effects have a tissue-specific direction, primarily in the vascular endothelium, gastrointestinal epithelium, and neurons.

Flavonoids and anthocyanins have a pronounced effect on the regulation of the inflammatory cascade. In a number of in vitro models, it has been established that they inhibit COX-2 expression and suppress the production of prostaglandins PGE2, and also regulate the activity of LOX enzymes, reducing leukotriene synthesis. Simultaneously, inhibition of the activity of the transcription factor NF-κB, which controls the expression of key inflammatory cytokines — IL-1β, IL-6, and TNF-α — is recorded. These mechanisms are accompanied by a decrease in the expression of adhesion molecules (ICAM-1, VCAM-1) and limitation of transendothelial migration of neutrophils.

Compounds of crowberry modulate the immune response through enhanced phagocytosis, activation of T-lymphocytes, and induction of interferon production, in particular IFN-γ. This effect is mediated through effects on innate immunity receptors (TLR2 and TLR4) and activation of JAK/STAT and MAPK signaling pathways. Phenolic compounds also demonstrate the potential to suppress NLRP3 inflammasome activation in macrophages.

At the neuronal level, anthocyanins and flavonoids demonstrate neuromodulatory activity, binding to GABA and serotonin receptors (5-HT₁A, 5-HT₂C), exerting an inhibitory effect on neuronal excitation in the prefrontal cortex. These compounds also inhibit monoamine oxidase (MAO) activity, contributing to the stabilization of monoamine levels, including dopamine and serotonin, which has been confirmed in neuropharmacological models.

Components of crowberry have the potential to modulate vascular tone, indirectly affecting endothelial receptors that regulate nitric oxide (NO) production. This is accompanied by improved endothelial function, reduced vasoconstriction, and stabilization of microcirculation.

Pharmacologically significant are also the effects on the epidermal barrier. Anthocyanins and flavonoids inhibit the activity of MMP-1 and MMP-9 — metalloproteinases responsible for the degradation of collagen and elastin. At the same time, they stimulate the expression of genes encoding filaggrin and involucrin — structural proteins responsible for the density and integrity of the epidermis. These actions are enhanced by the antioxidant protection of lipid components of the stratum corneum.

Modulation of lipid and carbohydrate metabolism occurs through the activation of AMPK and suppression of the activity of lipogenesis enzymes. Crowberry flavonoids can influence glucose transport and insulin receptor sensitivity in peripheral tissues, which has been confirmed in a number of experimental models.

References:
https://pubmed.ncbi.nlm.nih.go...
https://www.ncbi.nlm.nih.gov/p...
https://www.sciencedirect.com/...
https://link.springer.com/arti...
https://www.mdpi.com/1420-3049...

Synergy — Empetrum sibiricum

In vitro and in vivo studies demonstrate synergy between crowberry extracts and other phytocomponents possessing antioxidant, anti-inflammatory, and immunomodulatory activity. The combined use of anthocyanin-containing crowberry extracts and green tea polyphenols exhibits a potentiating effect in inhibiting COX-2 and NF-κB expression, which confirms an additive anti-inflammatory effect at the macrophage level. Similar synergy is also observed with combined exposure to extracts of Vaccinium myrtillus and Aronia melanocarpa, which enhances the suppression of lipid peroxidation and increases the expression of antioxidant enzymes.

Pharmacological compatibility with fat-soluble fractions (for example, tocopherols and unsaturated fatty acids) demonstrates protective synergy with respect to epidermal cells. The use of crowberry in combination with sea buckthorn oil, blackcurrant oil, or grape seed oil leads to enhanced skin regeneration and restoration of the epidermal barrier through the combined activation of PPAR-γ receptors and inhibition of MMP-1.

Immunological synergy has been recorded when used together with β-glucans (from mushrooms and oats), which enhance the production of interleukin-12 and interferon-gamma in the presence of crowberry extract. This indicates functional interaction through TLR receptors and the JAK/STAT cascade, contributing to a more pronounced activation of the innate and adaptive immune response.

Crowberry flavonoids also demonstrate an additive effect when used together with curcumin, resveratrol, and ginkgo extract with respect to the regulation of vascular tone and antihypoxic activity. Such a combination enhances nitric oxide production by the endothelium, reduces oxidative damage, and improves microcirculation, especially under hypoxic conditions.

References:
https://www.ncbi.nlm.nih.gov/p...
https://pubmed.ncbi.nlm.nih.go...
https://www.sciencedirect.com/...
https://link.springer.com/arti...
https://www.mdpi.com/1420-3049...

Geography of Use and Traditional Medicine — Empetrum sibiricum

Empetrum sibiricum, as a local form of the widespread black crowberry (Empetrum nigrum), was traditionally used in the folk medicine of the northern, Siberian, and Arctic regions of Eurasia, including the territory of Siberia, Kamchatka, Chukotka, northern Kazakhstan, Mongolia, as well as the Arctic zone of Eastern Europe. Mentions of the use of crowberry in folk healing practices are found among the Evenks, Khanty, Nenets, Yakuts, Komi, and in the North Russian village tradition.

Berries collected in the wild were used for food, and also processed into infusions and decoctions, which were used as drinks, compresses, and lotions. In the tradition of the Komi and Russian Old Believers, a decoction of berries and leaves was considered a strengthening and cleansing remedy for the body. In Evenki and Yakut culture, crowberry was used as part of ritual nutrition during the winter solstice, and its berries could act as a component of ritual treats associated with restoring strength and resistance to cold.

Among the peoples of the North, including the Chukchi and Koryaks, crowberry berries were consumed as a source of energy and maintenance of vitality in the conditions of the tundra climate. In Chukotka, rituals are known in which crowberry fruits were placed in the hearth or carried in pouches as protection from the evil spirits of fog and disease. Among the Khanty, crowberry was used as a protective plant — branches of the plant could be hung over the entrance to the dwelling, especially during the season of northern winds and epidemics.

In Siberian shamanic practices, crowberry leaves were often part of herbal mixtures used externally in the form of poultices and compresses. Among the Old Believers of Transbaikalia, there was a belief that an infusion of crowberry could "purify the mind" and "calm the heart," which indicates potential use for mental disorders and anxiety states, although the formulations were of a symbolic-religious nature.

In Mongolian folk medicine, the plant was used in the form of thick extracts, which were rubbed into the skin for seasonal imbalances of "wind and phlegm," according to the classification of Tibetan medicine. In some remote areas of northern Mongolia, crowberry berries were considered sacred and offered to the spirit-masters of the area on stone altars (ovoo), especially in places with cold springs.

Among the peoples of the North, crowberry could also be part of smoking and fumigating mixtures, which were used in dwellings after the death of a family member or at the birth of a child. The fruits of the plant were also used as a dye — the juice of the berries was added to ritual drinks and fabrics, creating a characteristic bluish-black hue.

Thus, Siberian crowberry has a rich ethnobotanical history, covering both medicinal and ritual use. In various cultures, it symbolized the power of cold, endurance, purification, and restoration of life balance.