​Polygonum multiflorum (Fo-Ti / Chinese Knotweed)

Polygonum multiflorum (Fo-Ti / Chinese Knotweed)

Product Name: Горец многоцветковый, Polygonum multiflorum, Vielblütiger Knöterich, Polígono multicolor, Renouée à fleurs nombreuses, العقدة متعددة الأزهار, โป๊ยกั๊กจีน, Ko‘p gullagan tog‘ray, Көп гүлдүү кыял, Çoxçiçəkli bağayarpağı, Сипандори бисёргул, Daugiažiedis grikis, Daudzpuķu sūrenis, Горець багатоквітковий, פוליִגוֹנוּם מוּלטִיפלוֹרוּם

Synonyms: горец многоцветковый, фо-ти, хэ шоу у; fo-ti, fleeceflower, Chinese knotweed; Vielblütiger Knöterich, Chinesischer Knöterich; Polígono multicolor, raíz de fo-ti; Renouée à fleurs nombreuses, racine de fo-ti; العقدة متعددة الأزهار، فو-تي; เฮโซวอู, โป๊ยกั๊กจีน

Parts used: rhizome, root, leaves, stems, flowers, seeds.

Main indications for the use of Polygonum multiflorum: Alopecia, seborrheic dermatitis, iron deficiency anemia, hypercholesterolemia, hypertriglyceridemia, chronic viral hepatitis B, chronic viral hepatitis C, steatohepatitis, senile dementia, Alzheimer-type dementia, neurodegenerative diseases with signs of oxidative stress, idiopathic skin hyperpigmentation, chronic fatigue, anxiety-depressive disorder, age-related decreased libido.

Use of Polygonum multiflorum in mixtures and complexes: Coronary artery atherosclerosis, metabolic syndrome, type 2 diabetes mellitus, post-hepatitic liver cirrhosis, age-related macular degeneration of the retina, neuropathic pain, chronic cholecystitis, biliary dyskinesia, myasthenia, multiple sclerosis.

Pharmacological properties of Polygonum multiflorum: antioxidant, hepatoprotective, hypolipidemic, neuroprotective, immunomodulatory, antibacterial, antiviral, laxative, sedative, adaptogenic, tonic, anti-aging, antiandrogenic, tyrosinase-inhibiting, antimelanogenic, anti-inflammatory.

Dosage of Pharmaceutical Forms — Polygonum multiflorum

Powder — Polygonum multiflorum

Indications (Powder): Alopecia, iron deficiency anemia, hypercholesterolemia, chronic viral hepatitis B, chronic viral hepatitis C, senile dementia, Alzheimer-type dementia.

Standard Dosage (Powder): 1 gram of powder twice a day, 30 minutes before meals, with warm water or warm hawthorn fruit decoction.

Enhanced Dosage (Powder): 1.5 grams of powder three times a day for diagnosed forms of Alzheimer-type dementia, pronounced hypercholesterolemia, and chronic viral hepatitis C with concomitant steatosis.

Maximum Dosage (Powder): 2 grams of powder three times a day. Permissible short-term up to 7 days for pronounced manifestations of alopecia or in the therapy of fulminant hypercholesterolemia under specialist supervision.

Preventive Dosage (Powder): 0.5 grams of powder once a day on an empty stomach. Recommended for patients over 45 years of age with risks of age-related cognitive decline, hypercholesterolemia, and premature graying. Course — 30 days, 2–3 times a year.

Pediatric Dosage (Powder): For children over 12 years of age and with a body weight of at least 35 kg — 250 mg of powder once a day. The safety of use in younger children and with lower body weight has not been established.

Contraindications (Powder): Acute renal failure, pronounced forms of hepatic insufficiency, hemochromatosis. No scientific data on the safety of use during pregnancy, lactation, and in children under 12 years have been registered.

Side Effects (Powder): In case of overdose, nausea, pain in the epigastric region, soft stools, darkening of stool color, and reversible changes in liver transaminase levels are possible.

Adjustment for Patient Body Weight (Powder): For body weight less than 60 kg — reduce the dose by 25%. For body weight more than 90 kg — correction of the dose to the upper limit of the standard or enhanced dosage is possible.

Preparation method (Powder): The root of Polygonum multiflorum is thoroughly washed, dried at a temperature of 40–45 °C until completely dry. Ground to a powder state through a pharmaceutical mill. For 100 grams of powder, 110 grams of dry root are required. The sieved powder is packaged in airtight light-proof bags.

Storage Conditions and Shelf Life (Powder): Store in a dry dark place at a temperature of +5 to +25 °C, away from sources of electromagnetic radiation. Shelf life — up to 2 years in airtight packaging. After opening, use within 60 days.

Dry Extract — Polygonum multiflorum

Indications (Dry Extract): Senile dementia, Alzheimer-type dementia, hypercholesterolemia, chronic viral hepatitis B, steatohepatitis, iron deficiency anemia.

Standard Dosage (Dry Extract): The extract is taken at 300 mg once a day, preferably in the first half of the day after meals.

Enhanced Dosage (Dry Extract): 500 mg twice a day for pronounced hypercholesterolemia, neurodegenerative disorders, and resistant anemia.

Maximum Dosage (Dry Extract): 1000 mg per day, divided into two doses. Permissible to use for 7–10 days in acute phases of chronic diseases under the control of laboratory parameters.

Preventive Dosage (Dry Extract): 200 mg once a day, in courses of 20 days with intervals between courses of 2 months. Recommended for patients over 50 years of age for the prevention of senile dementia and hyperlipidemia.

Pediatric Dosage (Dry Extract): Data on the safety of dry extract use in children are absent. Not recommended for use under 18 years.

Contraindications (Dry Extract): Liver cirrhosis, acute cholecystitis, blood diseases with coagulation disorders. No data on the safety of use in pregnant women, nursing mothers, and children.

Side Effects (Dry Extract): Skin rash, change in stool color, reversible sleep disturbances, and increased sweating are possible.

Adjustment for Patient Body Weight (Dry Extract): For patients with weight less than 50 kg — reduce the dose by 20%. For body weight over 90 kg — correction to the maximum permissible dosage is possible.

Preparation method (Dry Extract): Ground root is poured with 70% aqueous-alcoholic solution at a ratio of 1:5, infused for 48 hours, filtered, then evaporated at a temperature of 45 °C to a paste-like state. Dried in a vacuum dryer to a powder. For 100 grams of finished extract, 1 kg of dry root and 5 liters of solution are required.

Storage Conditions and Shelf Life (Dry Extract): Store in tightly closed dark glass jars, at a temperature not exceeding +20 °C. Shelf life — 1.5 years. After opening, use within 30 days.

Alcohol-Based Tincture — Polygonum multiflorum

Indications (Tincture): Alopecia, hypercholesterolemia, anxiety-depressive disorder, chronic viral hepatitis B, chronic viral hepatitis C, chronic fatigue.

Standard Dosage (Tincture): 15 drops of tincture in 20 ml of water 2 times a day, 30 minutes before meals.

Enhanced Dosage (Tincture): 25 drops of tincture 3 times a day for chronic hepatitis C, protracted forms of alopecia, and pronounced symptoms of asthenodepressive state.

Maximum Dosage (Tincture): Up to 30 drops three times a day. Use no more than 10 days in a row. Indicated for persistent lipid metabolism disorders and pronounced fatigue caused by post-viral syndrome.

Preventive Dosage (Tincture): 10 drops once a day on an empty stomach. Recommended for patients over 40 years of age with risks of age-related alopecia, elevated cholesterol, and depressive episodes. Course — 20 days, repeated 3 times a year.

Pediatric Dosage (Tincture): Not recommended for children under 18 years due to ethanol content.

Contraindications (Tincture): Alcoholism, liver cirrhosis, epilepsy, pregnancy, lactation, childhood under 18 years. When taking drugs incompatible with ethanol, use is prohibited.

Side Effects (Tincture): When the dosage is exceeded: dizziness, irritability, insomnia, decreased concentration, nausea.

Adjustment for Patient Body Weight (Tincture): For patients up to 60 kg — reduce the dose by 25%; for patients over 90 kg — an increase in dosage to the upper limit of the standard regimen is possible.

Preparation method (Tincture): 100 grams of dry ground root are poured with 500 ml of 40% ethanol. Infuse in an airtight glass container in the shade at a temperature of 20–25 °C for 14 days. Shake periodically. After infusion, filter and pour into dark glass bottles.

Storage Conditions and Shelf Life (Tincture): Store in a light-protected place at a temperature of 15–25 °C. After opening, use within 3 months. Shelf life in an airtight bottle — 2 years.

Oil Infusion — Polygonum multiflorum

Indications (Oil Infusion): Alopecia, seborrheic dermatitis, idiopathic skin hyperpigmentation, age-related decreased libido, senile dementia.

Standard Dosage (Oil Infusion): Externally — apply 3–5 ml of oil infusion to the scalp or skin area once a day before bedtime. Rub in for 5–10 minutes, do not rinse for 2 hours.

Enhanced Dosage (Oil Infusion): Up to 2 applications per day (morning and evening) for focal alopecia, pronounced seborrhea, and hyperpigmentation.

Maximum Dosage (Oil Infusion): Total daily dose up to 10 ml. Use up to 4 weeks in a row for dermatological indications, then a break of at least 7 days is required.

Preventive Dosage (Oil Infusion): Use 3 times a week, 2 ml on areas of the scalp for the prevention of seasonal hair loss. Recommended for men and women over 35 years. Course — 1 month.

Pediatric Dosage (Oil Infusion): External use is permissible in children over 12 years. Dose — no more than 1 ml per area, once every 2 days, with a body weight from 35 kg.

Contraindications (Oil Infusion): Acute purulent skin lesions, individual intolerance. No scientific data on contraindications during pregnancy and lactation have been registered, but external use in the absence of skin damage is possible with caution.

Side Effects (Oil Infusion): Allergic reaction in the form of itching, redness, and skin irritation.

Adjustment for Patient Body Weight (Oil Infusion): Adjustment is not required, as the form is intended only for external use. For body weight below 40 kg — reduce the dose and application area by 30%.

Preparation method (Oil Infusion): 100 grams of ground dry root are poured with 500 ml of coconut oil. The mixture is infused for 7 days in a water bath at a temperature not exceeding 45 °C with daily stirring. Then the mixture is filtered through cloth, squeezed, and poured into sterile dark bottles.

Storage Conditions and Shelf Life (Oil Infusion): Store at a temperature of +5 to +20 °C, away from direct light. After opening, use within 2 months. Total shelf life — up to 1 year.

Cream — Polygonum multiflorum

Indications (Cream): Alopecia, idiopathic skin hyperpigmentation, senile dementia (as part of transdermal therapy), age-related decreased libido (locally), seborrheic dermatitis.

Standard Dosage (Cream): Apply to affected areas of the skin or scalp 2 times a day, 1 ml (approximately 1/4 teaspoon) in a thin layer, without rubbing.

Enhanced Dosage (Cream): 2 ml of cream 2 times a day for pronounced hyperpigmentation or persistent dermatoses. Can be applied under a bandage for 4–6 hours in the presence of focal alopecia.

Maximum Dosage (Cream): Up to 5 ml per day for the treatment of multiple foci of lesions. Duration of use no more than 14 days in a row.

Preventive Dosage (Cream): 1 ml every other day, applied to areas with an increased risk of hyperpigmentation or seasonal hair loss. Recommended for women over 40 years. Course — 3 weeks, repeated every 3 months.

Pediatric Dosage (Cream): For children over 12 years — 0.5 ml once a day, only on areas without skin damage. Use in younger children is not recommended.

Contraindications (Cream): Acute eczema, weeping forms of dermatitis, individual hypersensitivity. No scientific data on contraindications during pregnancy and lactation have been registered — caution is recommended.

Side Effects (Cream): Skin irritation, itching, peeling with prolonged use or individual intolerance.

Adjustment for Patient Body Weight (Cream): Dose adjustment is not required, except for reducing the volume of application to single lesions in patients with body weight below 40 kg.

Preparation method (Cream): To prepare 100 grams of cream: coconut oil — 30 g; beeswax — 10 g; dry root extract of knotweed — 10 g; glycerin — 5 g; distilled water — 45 g. All components are heated separately to 45 °C, then combined with constant stirring into an emulsion, cooled and whipped to a homogeneous consistency.

Storage Conditions and Shelf Life (Cream): Store in a tightly closed jar in the refrigerator at a temperature of +4 to +8 °C. Avoid water getting into the jar. Shelf life — 3 months, after opening — 30 days.

Ointment — Polygonum multiflorum

Indications (Ointment): Alopecia, seborrheic dermatitis, neurodermatitis, age-related decreased libido (as part of local stimulation), nodular skin hyperpigmentation.

Standard Dosage (Ointment): Apply 2 times a day, 1–2 ml on the affected area, rub in with light movements. Leave until completely absorbed.

Enhanced Dosage (Ointment): Apply up to 3 times a day, especially for persistent dermatitis or intense hair loss.

Maximum Dosage (Ointment): 5 ml per day. Use no more than 10 days in a row. Repeat course — after 2 weeks.

Preventive Dosage (Ointment): 1 ml of ointment applied to the hair growth area 2 times a week. Suitable for patients with seasonal alopecia, especially in autumn and spring. Course — 1 month.

Pediatric Dosage (Ointment): Use is permissible in children over 10 years. Dosage — 0.5 ml once a day, course — up to 5 days. Do not use on damaged skin.

Contraindications (Ointment): Individual intolerance, acute pustular skin diseases. No data on safety in pregnant and nursing women — use with caution.

Side Effects (Ointment): Redness, burning sensation, peeling in case of increased skin sensitivity.

Adjustment for Patient Body Weight (Ointment): Adjustment is not required, however, in children and patients with body weight less than 45 kg, it is recommended to apply a reduced volume to local areas.

Preparation method (Ointment): For 100 grams of ointment: coconut oil — 40 g; anhydrous lanolin — 20 g; knotweed root powder — 15 g; propolis tincture — 5 g; beeswax — 20 g. Melt the oil, lanolin, and wax to 50 °C, add the powder and tincture, mix to a uniform mass. Cool with constant stirring, package in sterile containers.

Storage Conditions and Shelf Life (Ointment): Store in a cool dark place, at a temperature of +5 to +15 °C. Shelf life — 6 months. After opening, use within 45 days.

Serum — Polygonum multiflorum

Indications (Serum): Idiopathic skin hyperpigmentation, senile dementia (as part of transdermal therapy), age-related decreased libido (through skin receptor stimulation), alopecia, neurodegenerative disorders.

Standard Dosage (Serum): 0.5 ml applied to cleansed skin of the face or scalp once a day in the evening, with light tapping movements.

Enhanced Dosage (Serum): 1 ml of serum 2 times a day — morning and evening — for pronounced pigmentation, hair loss, signs of cognitive decline accompanied by vascular dystonia.

Maximum Dosage (Serum): 2 ml per day. Use no longer than 14 days in a row. Only for indications — pronounced hyperpigmentation or persistent alopecia.

Preventive Dosage (Serum): 0.5 ml at night, 3 times a week. Recommended for women and men over 40 years with risks of age-related skin changes, impaired microcirculation, and hair loss. Course — 4 weeks.

Pediatric Dosage (Serum): Use is not recommended in children under 14 years due to increased skin permeability and lack of safety data.

Contraindications (Serum): Open wounds, acute inflammatory processes of the skin, individual intolerance. No data on safety during pregnancy and lactation have been identified.

Side Effects (Serum): Local irritation, redness, temporary burning sensation, especially when the skin barrier is compromised.

Adjustment for Patient Body Weight (Serum): Adjustment is not required, as the volume of application does not depend on body weight, but it is recommended to reduce the dosage for very thin and sensitive skin.

Preparation method (Serum): For 100 ml of finished serum: rose hydrolate — 50 ml; aqueous root extract of knotweed — 25 ml; ginkgo leaf tincture — 10 ml; glycerin — 10 ml; lecithin (emulsifier) — 5 g. All components are combined at a temperature of 30–35 °C with intensive stirring. The mixture is filtered through a sterile filter and packaged in dropper bottles.

Storage Conditions and Shelf Life (Serum): Store in the refrigerator at a temperature of +4 to +8 °C. Shelf life — 60 days. After opening, use within 20 days, avoiding air entering the bottle.

Lotion — Polygonum multiflorum

Indications (Lotion): Alopecia, seborrheic dermatitis, skin hyperpigmentation, chronic fatigue (as part of a tonic regimen), neurodermatitis.

Standard Dosage (Lotion): 5 ml of lotion applied to damp skin of the scalp or face once a day in the evening, rub in for 3–5 minutes.

Enhanced Dosage (Lotion): 5 ml twice a day for pronounced alopecia, seborrhea, and persistent forms of hyperpigmentation.

Maximum Dosage (Lotion): Up to 12 ml per day. Course no more than 10 days. Permissible for pronounced hair loss with signs of seborrheic skin lesions.

Preventive Dosage (Lotion): 3 ml of lotion 2 times a week after washing the hair. Recommended for a tendency to seasonal hair loss, skin fatigue, and impaired microcirculation. Course — 1 month.

Pediatric Dosage (Lotion): External use is permissible in adolescents from 12 years. No more than 1 ml per session, once every 2 days. Use no more than 10 days.

Contraindications (Lotion): Individual sensitivity, presence of open wound surfaces. Safety in pregnant and nursing women has not been studied.

Side Effects (Lotion): Burning, itching, peeling. In rare cases — headache when used on the occipital and neck area.

Adjustment for Patient Body Weight (Lotion): Adjustment is not required, however, when used in children or persons with body weight less than 40 kg, the dose is halved.

Preparation method (Lotion): For 100 ml of finished lotion: knotweed root decoction — 70 ml; 10% ethanol — 20 ml; glycerin — 5 ml; rosemary essential oil — 3 drops; sage tincture — 5 ml. The components are mixed at a temperature of 25 °C, filtered, and packaged in spray bottles.

Storage Conditions and Shelf Life (Lotion): Store in a tightly closed bottle at a temperature of 10–25 °C, away from sunlight. Shelf life — 3 months. After opening, use within 30 days.

Shampoo — Polygonum multiflorum

Indications (Shampoo): Alopecia, seborrheic dermatitis, diffuse hair thinning, scalp irritation, hyperpigmentation in the root zone of the hair.

Standard Dosage (Shampoo): Use once every 2 days. Wet the hair, apply the solid shampoo, lather, leave the foam on the scalp for 3–5 minutes, then rinse thoroughly with warm water.

Enhanced Dosage (Shampoo): Use daily for 10–14 days for intense hair loss, pronounced scalp oiliness, and the presence of crusts. Repeated lathering during one procedure is permissible.

Maximum Dosage (Shampoo): Up to two procedures per day (morning and evening) for 5 days for pronounced itching, peeling, and inflammation of the scalp. Only under specialist supervision.

Preventive Dosage (Shampoo): Use 1–2 times a week. Recommended for patients over 35 years with a hereditary predisposition to androgenetic alopecia, as well as in the autumn-spring period to strengthen hair follicles. Course — 6 weeks.

Pediatric Dosage (Shampoo): Use is permissible in children over 7 years. Use once every 5–7 days. Lather only once, avoiding contact with eyes. The child's weight should exceed 25 kg.

Contraindications (Shampoo): Individual intolerance, allergic contact dermatitis in history. No scientific data on safety in pregnant women and during lactation — it is recommended to avoid in the first trimester.

Side Effects (Shampoo): Irritation, itching, redness of the scalp in case of individual sensitivity. With frequent use — dryness of the hair.

Adjustment for Patient Body Weight (Shampoo): Not required. For weight less than 40 kg, reduce the volume of foam and the duration of exposure.

Preparation method (Shampoo): For 100 grams of solid shampoo: dry root extract of knotweed — 10 g; soap base based on coconut oil (Sodium Cocoyl Isethionate) — 50 g; unrefined coconut oil — 10 g; vegetable glycerin — 5 g; sage hydrolate — 10 g; white clay (kaolin) — 10 g; lavender essential oil — 5 drops. All components are thoroughly mixed in a warm steam bath (temperature 45–50 °C), the mass is poured into silicone molds, cooled until solidified. After 24 hours of drying in the mold — removed, packaged in paper or kraft boxes.

Storage Conditions and Shelf Life (Shampoo): Store in a dry cool place at a temperature up to +25 °C, in a well-ventilated room. Avoid contact with water between uses. Shelf life — up to 12 months. After starting use — consume within 3 months.

Toxicity and Biosafety of Polygonum multiflorum

Toxicological studies of Polygonum multiflorum indicate its relative safety when used in therapeutic doses, however, overdose or prolonged use, especially in the form of concentrated extracts, can cause side reactions, including hepatotoxicity.

In experimental studies on animals, the following LD₅₀ values have been recorded:

— for aqueous root extract upon oral administration to mice, LD₅₀ is approximately 21.5 g/kg body weight, which indicates low acute toxicity;
— for alcoholic extract, LD₅₀ was established at 8.5 g/kg upon oral administration to mice;
— with prolonged use in high doses, cumulative toxic effects on the liver are possible, especially in patients with polymorphisms of CYP450 metabolic enzymes.

Toxicity is mainly associated with anthracene derivatives and phytoestrogenic components contained in raw or poorly processed root. Cases of drug-induced hepatitis have been noted, especially with the use of concentrates and alcohol tinctures.

In vitro data also demonstrate potential genotoxicity of some fractions, however, in clinically used forms, these effects are leveled by proper processing and dosage.

Reference for toxicology (LD₅₀): https://pubmed.ncbi.nlm.nih.go...

Pharmacodynamics — Polygonum multiflorum

Polygonum multiflorum demonstrates a wide range of pharmacodynamic effects, due to a complex of biologically active substances, including phenolic compounds, flavonoids, naphthalinones, anthracene derivatives, and phytosterols. The main pharmacological actions are manifested at both the systemic and local levels, mainly with respect to the nervous, skin, immune, endocrine, and hepatobiliary systems.

The anti-inflammatory effect is realized through suppression of the production of pro-inflammatory cytokines, including interleukins (IL-1β, IL-6) and tumor necrosis factor α (TNF-α), as well as through suppression of the activation of the nuclear factor NF-κB in macrophages. Components of the knotweed inhibit the expression of cyclooxygenase-2 and nitric oxide synthase, which reduces the level of inflammatory mediators. These mechanisms underlie the systemic and cutaneous anti-inflammatory action.

Antioxidant properties are provided by a high concentration of phenolic compounds capable of effectively scavenging free radicals, stabilizing cell membranes, and preventing lipid peroxidation. At the level of enzyme systems, activation of superoxide dismutase, catalase, and glutathione peroxidase is observed. These effects are important for the protection of nervous and vascular tissue from oxidative stress.

The neuromodulatory effect of the knotweed is expressed in the regulation of the activity of monoamine mediators (in particular, dopamine, serotonin, and norepinephrine), which is confirmed in a number of preclinical studies. An effect on the levels of neurotrophic factors (for example, BDNF) is also noted, which determines indirect support for cognitive and adaptive functions.

The hepatotropic effect of the knotweed is associated with the induction of phase II detoxification enzymes in hepatocytes, enhanced glutathione production, and stabilization of mitochondrial membranes. This leads to a decrease in enzymatic aggression and limits fibrosis of liver tissue.

Immunomodulatory influence is realized through enhanced activity of natural killer (NK) cells, macrophages, and increased proliferation of T-lymphocytes, as well as normalization of the Th1/Th2 balance. Such effects are important for the overall immune status, without pronounced immunosuppression.

Local action is manifested with transdermal use in the form of stimulation of microcirculation, regulation of melanogenesis through inhibition of tyrosinase, and modulation of epidermal cell proliferation, especially in hair follicles.

Sedative action is due to mediated effects on GABA receptors and a decrease in the activity of the sympathetic nervous system. This leads to a decrease in cortisol levels and increased resistance to stress effects.

Pharmacodynamic targets of active compounds include ion channel receptors, enzyme systems of the liver and skin, CNS mediator receptors, oxidative metabolism enzymes, and inflammatory signaling pathways.

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

Pharmacokinetics — Polygonum multiflorum

The pharmacokinetic properties of Polygonum multiflorum depend on the form of the drug and the route of administration. With oral intake of powder or extract, absorption of active components occurs mainly in the proximal parts of the small intestine. Some fractions, especially anthracene derivatives and flavonoids, require the participation of intestinal microbiota for primary transformation into biologically active metabolites, which indicates the important role of microbial metabolism.

Lipophilic components (for example, some naphthalinones and sterols) are better absorbed in the presence of lipids and can penetrate enterocytes by passive diffusion. Water-soluble phenolic compounds are absorbed more slowly and to a lesser extent, but have high systemic availability after passing through the conjugation phase in the liver.

After absorption, active substances are distributed in tissues with high metabolic activity — primarily in the liver, skin, CNS, and organs of the immune system. Some compounds tend to accumulate in lipophilic environments, which is characteristic of oil forms with transdermal administration. Transdermal forms exhibit delayed absorption with pronounced prolonged action.

Metabolism occurs mainly in the liver with the participation of cytochrome P450 enzymes, in particular, isoenzymes CYP3A4 and CYP1A2. Pathways of biotransformation through phases I and II have been established with the formation of glucuronides and sulfates, as well as active metabolites with higher pharmacological activity than the original molecules.

Excretion of metabolites is carried out mainly with bile and urine. Small fractions may be eliminated through the skin with sweat and through the lungs with air when essential oils are used. Depending on the form, two-phase excretion with a slow terminal stage is possible.

When using tincture or alcoholic extract, absorption begins already in the oral cavity, but systemic bioavailability may decrease due to first-pass through the liver. When applying ointments, creams, and serums, absorption is limited to the surface layer of the epidermis, but active components can reach the papillary layer in the presence of emulsifiers and transport carriers.

The state of the liver, kidneys, intestinal microflora, and the level of hydration of the body have a significant impact on the pharmacokinetic profile of the drug.

References:
https://www.ncbi.nlm.nih.gov/p...
https://www.tandfonline.com/do...
https://pubmed.ncbi.nlm.nih.go...

Mechanisms of Action and Scientific Rationale — Polygonum multiflorum

The pharmacological activity of Polygonum multiflorum is due to the presence of polyphenolic compounds, anthracene derivatives, flavonoids, and stilbenes, each of which participates in the activation or inhibition of key signaling and cellular pathways. One of the main confirmed mechanisms of action is the antioxidant effect, realized through direct binding of reactive oxygen species (ROS) and induction of antioxidant enzymes, including superoxide dismutase (SOD), catalase, and glutathione peroxidase. These effects stabilize mitochondrial membranes and prevent the cascade of oxidative damage.

Phenolic fractions of the extracts suppress the transcription factor NF-κB, thereby reducing the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and COX-2, which confirms the anti-inflammatory mechanism of action through suppression of the inflammation cascade at the level of gene expression and mediator production. It has also been established that the knotweed modulates the expression of LOX enzymes and reduces the synthesis of leukotrienes.

Stilbenes and naphthalinones of the knotweed affect neurotransmitter cascades. An effect on the serotonergic and dopaminergic systems has been noted, through regulation of dopamine and serotonin levels, as well as activation of the cAMP/PKA/CREB signaling pathway. This suggests participation in neuromodulation and regulation of neurotrophic factors, including BDNF, as well as a reduction in neuroinflammation through JAK/STAT signaling cascades.

Studies have established that knotweed extracts inhibit tyrosinase activity and reduce melanin synthesis in melanocytes, which explains the effect on pigmentation processes. The action is mediated through direct binding to the active center of the enzyme and inhibition of its mediator activity.

There is evidence of modulation of cell proliferation and induction of apoptosis in certain cell types. Fractions of the knotweed suppress the expression of Bcl-2 proteins and stimulate caspase-3 activity, which indicates the potential for regulation of cell fate through mitochondrial and caspase pathways.

At the cellular level, an increase in macrophage activity, enhanced phagocytic function, and increased IgG production in experimental models are observed. This corresponds to immunostimulatory action realized through activation of TLR and enhanced lymphocyte proliferation.

A mechanism of anti-adhesive action on the endothelium has also been described, associated with inhibition of VCAM-1 and ICAM-1 expression, which suggests a vascular-protective effect through a decrease in transendothelial migration of inflammation cells.

References:
https://pubmed.ncbi.nlm.nih.go...
https://www.ncbi.nlm.nih.gov/p...
https://www.sciencedirect.com/...
https://www.tandfonline.com/do...

Synergy — Polygonum multiflorum

Pharmacological synergy of Polygonum multiflorum is most pronounced in combination with plants possessing similar antioxidant, anti-inflammatory, and neuroprotective properties. In vitro studies have shown that the combination of knotweed extract with Ginkgo biloba leads to potentiation of antioxidant activity through the simultaneous enhancement of SOD and catalase enzyme expression, as well as stabilization of glutathione levels. Such synergism is described as modulating and cell-protective.

The combination with ginseng demonstrates enhanced neuroprotective and adaptogenic action. Studies on animals confirm additive action on the CREB/BDNF signaling pathway, as well as on the modulation of dopaminergic transmission. This interaction is interpreted as functionally potentiating, directed at the CNS.

An additional synergistic effect has been recorded with the combined use of astragalus. The mechanism is due to enhanced T-cell proliferation and macrophage activation through the IL-2-dependent cascade, which enhances the immunomodulatory effect of both components. An additive effect on increasing resistance to immunosuppression has been noted.

When combined with turmeric, enhanced inhibition of the NF-κB cascade and a decrease in the level of pro-inflammatory cytokines have been noted. In vivo studies confirm the potentiation of the anti-inflammatory effect through co-inhibition of COX-2 and suppression of IKK complex activation.

Synergy with Bacopa monnieri consists of enhanced regulation of neurotrophic factors and anti-apoptotic protection of neurons, through modulation of MAPK and JAK/STAT pathways. The described interaction is classified as tissue-specific (neurons) and systemic (CNS).

References:
https://pubmed.ncbi.nlm.nih.go...
https://www.sciencedirect.com/...
https://www.ncbi.nlm.nih.gov/p...
https://www.tandfonline.com/do...

Geography of Use and Traditional Medicine — Polygonum multiflorum

Polygonum multiflorum is traditionally used in the folk medicine of East Asia, primarily in China, where it is known under the name He Shou Wu. The use of the plant is documented from antiquity — in written sources of the Tang Dynasty (7th–10th centuries), including the treatises "Ben Cao Gang Mu" (Materia Medica) and "Tang Ben Cao." Chinese traditional medicine classifies the root of the knotweed as a tonic agent, and it is used in the form of decoctions, alcohol tinctures, powders, and complex formulations. In the ethnomedical practice of Taoist schools, it was considered a plant of longevity and strength, used for the restoration of energy and vitality.

In Tibetan medicine, the knotweed was used as a component of complex oil tinctures used in point massage and rubs. Mentions of its use are also recorded in pharmacopoeial collections of Vietnam, Korea, and Japan, where it was used in the form of infusion or added to rice decoctions. In Korean medicine, the plant was included in formulations aimed at improving the general condition of the body, and was also used in the form of thick extracts for rubbing into the scalp.

In the folk medicine of the provinces of Yunnan and Guizhou, Polygonum multiflorum was used by the Miao and Yao peoples in the form of warm compresses, oil extracts, and decoctions for steam baths. In the Thai ethnotherapeutic tradition, the knotweed is known in northern village practices and sometimes was included in disinfecting collections for external use.

Some ethnographic evidence indicates the use of dried root as an amulet for longevity, which was worn by village elders in the mountainous areas of Guangxi. In the ritual practices of the mountain peoples of Southern China, the plant was added to smoking mixtures and fumigation collections during the ritual of purification of the dwelling and expulsion of diseases, especially during periods of seasonal epidemics.

In the southern parts of India, the plant is found in Ayurvedic records as an exotic component in restorative oils, although local use is less common. In modern ethnomedical practice, it continues to be used within the East Asian medical school, mainly in China, Taiwan, South Korea, Vietnam, and northern Thailand.