Angelica gigas (Giant Angelica)

Angelica gigas (Giant Angelica)

Product Name: Дудник гигантский, Angelica gigas, Koreanische Engelwurz, Angélica coreana, Angélique de Corée, أنجليكا جيجاس, โกฐหัวบัว, Koreyaning archangeli, Ажыке периши, Koreya mələyi, Фариштаи кореягӣ, Korėjos angelika, Korejas eņģeļzieds, Корейський дягель, קוריאנית אנג'ליקה

Synonyms: Дудник корейский, Angelica koreana, Korean angelica, Purple Parsnip, Dangquai Korean dang-gui, Koreanische Engelwurz, Angélica coreana, Angélica de Corea, أنجيليكا كوريانا, โกฐหัวบัว, Корейский дягель, корейский дягиль, женский женьшень, Кудзу для женщин, สมุนไพรบำรุงเลือด, สมุนไพรฮอร์โมนเพศหญิง

Parts used: root, aerial part, seeds, leaves, flowers, fruits, stems, root extract, aerial part extract, root powder, juice — root.

Main indications for the use of Angelica gigas: Dysmenorrhea, climacteric syndrome, uterine fibroids, endometriosis, benign prostatic hyperplasia, iron deficiency anemia, postmenopausal psychoemotional disorders, hypertensive disease, osteoporosis, chronic hepatitis, ischemic heart disease, neuroinflammatory diseases, depression, hormone-dependent breast tumors, prostate cancer, chronic inflammatory bowel diseases.

Use of Angelica gigas in mixtures and complexes: Alzheimer's disease, type 2 diabetes mellitus, obesity, hyperlipidemia, chronic pancreatitis, herpesvirus infection, chronic gastritis, helminthic infestation, irritable bowel syndrome, chronic fatigue, anorexia, acne, vitiligo, hypothyroidism.

Pharmacological properties of Angelica gigas: estrogen-like, antidepressant, anxiolytic, hepatoprotective, antioxidant, neuroprotective, antitumor, antiangiogenic, anti-inflammatory, analgesic, antispasmodic, immunomodulatory, antibacterial, antiviral, hypolipidemic, vasodilating, antiplatelet, adaptogenic, cytotoxic, insulin-like.

Dosage of Pharmaceutical Forms — Angelica gigas

Powder — Angelica gigas

Indications (Powder): Dysmenorrhea, climacteric syndrome, endometriosis, iron deficiency anemia, chronic hepatitis, benign prostatic hyperplasia, osteoporosis, depression, hormone-dependent breast tumors.

Standard Dosage (Powder): 0.5 grams 2 times a day after meals, with warm water. Duration of intake is 14 days with a 7-day break.

Enhanced Dosage (Powder): 1 gram 2 times a day for diagnoses: endometriosis, uterine fibroids, and hormone-dependent breast tumors. Course of use 21 days, after which a break of at least 10 days is required.

Maximum Dosage (Powder): 1.5 grams 2 times a day is permissible in conditions of intensive therapy for dishormonal tumors under medical supervision. Course duration no more than 10 days.

Preventive Dosage (Powder): 0.3 grams once a day for 10 days monthly. Recommended for women with perimenopausal changes, patients with post-hepatitis conditions, mild anemia, and during the recovery period after pelvic organ surgeries.

Pediatric Dosage (Powder): Intake is permissible from 12 years with a body weight of at least 40 kg, at a dose of 0.2 grams once a day. Recommended only for girls at the onset of the menstrual cycle with pronounced pain syndrome.

Contraindications (Powder): Pregnancy, lactation, hyperestrogenic conditions, individual hypersensitivity. No scientific data on contraindications in children under 12 years have been registered.

Side Effects (Powder): Nausea, increased menstrual bleeding, dyspepsia. In case of overdose, headache, agitation, and tachycardia are possible.

Adjustment for Patient Body Weight (Powder): For body weight below 60 kg — reduction of dosage by 25%. For body weight above 80 kg — increase by 20% of the standard dosage.

Preparation method (Powder): Take 100 grams of dry root of Angelica gigas, grind to a powder state in a laboratory mill. Sieve through a sieve with a mesh diameter of 0.5 millimeters. Package in an airtight container. Without heat treatment.

Storage Conditions and Shelf Life (Powder): Store in a tightly closed glass container in a dark dry place at a temperature of 10 to 25 degrees Celsius. Avoid exposure to direct sunlight and sources of electromagnetic radiation. Shelf life up to 24 months. After opening, use within 60 days.

Dry Extract — Angelica gigas

Indications (Dry Extract): Climacteric syndrome, osteoporosis, depression, benign prostatic hyperplasia, neuroinflammatory diseases, chronic inflammatory bowel diseases.

Standard Dosage (Dry Extract): 200 milligrams 2 times a day, 30 minutes before meals. Duration of intake — 21 days.

Enhanced Dosage (Dry Extract): 400 milligrams 2 times a day for 14 days for neuroinflammatory diseases and pronounced postmenopausal disorders.

Maximum Dosage (Dry Extract): 500 milligrams 2 times a day for no more than 10 days in a row. Used only under medical supervision for hormone-dependent tumors.

Preventive Dosage (Dry Extract): 100 milligrams once a day for 14 days every 2 months. Recommended for perimenopausal women, patients with chronic gastritis, and mild anemia.

Pediatric Dosage (Dry Extract): Permissible from 12 years and with a body weight of at least 45 kg, 100 milligrams once a day for 5 days, only as prescribed by a specialist.

Contraindications (Dry Extract): Pregnancy, lactation, individual intolerance, estrogen-dependent tumors. Safety for children under 12 years has not been established.

Side Effects (Dry Extract): Dizziness, skin rashes, increased anxiety, dyspeptic disorders.

Adjustment for Patient Body Weight (Dry Extract): For body weight below 50 kg — reduce the dosage by 20%. For body weight above 80 kg — increase the dosage by 15%.

Preparation method (Dry Extract): Grind 500 grams of dry root of Angelica gigas. Conduct aqueous extraction in distilled water at a temperature of 80°C for 3 hours. Filter, evaporate to 1/5 of the volume in a water bath, dry in a drying chamber at a temperature of 40°C to obtain a dry extract. Grind the resulting extract to a powder state.

Storage Conditions and Shelf Life (Dry Extract): Store in tightly closed packaging, in a dry, light-protected place at a temperature of 5 to 25 degrees Celsius. Shelf life — 24 months. After opening, use within 30 days.

Alcohol-Based Tincture — Angelica gigas

Indications (Tincture): Dysmenorrhea, uterine fibroids, depression, chronic hepatitis, benign prostatic hyperplasia, climacteric syndrome, neuroinflammatory diseases.

Standard Dosage (Tincture): 20 drops 2 times a day, diluted in 50 milliliters of warm water, 30 minutes before meals. Course of intake 14 days with a 7-day break.

Enhanced Dosage (Tincture): 30 drops 2 times a day for 10–14 days for neuroinflammatory conditions, depressive disorders, and climacteric vasomotor symptoms.

Maximum Dosage (Tincture): 40 drops 2 times a day, no more than 7 days in a row, for severe forms of climacteric syndrome and pronounced hormone-dependent hyperplasia. Medical supervision is required.

Preventive Dosage (Tincture): 10 drops once a day for 7 days every 2 months. Recommended for premenopausal women, patients with chronic hepatitis in remission, and men with mild benign prostatic hyperplasia.

Pediatric Dosage (Tincture): Not recommended for children under 14 years. From 14 years, intake of 5–10 drops once a day is possible under strict supervision. Safety of intake has not been scientifically confirmed.

Contraindications (Tincture): Pregnancy, lactation, liver diseases in the stage of decompensation, alcoholism, childhood under 14 years. Contraindicated in estrogen-dependent tumors.

Side Effects (Tincture): Gastric pain, headache, irritability, increased bleeding, sensation of heat.

Adjustment for Patient Body Weight (Tincture): Patients with body weight less than 50 kilograms — reduce the dosage by 25%. Patients with body weight more than 80 kilograms — an increase in dosage to 30% is permissible under medical supervision.

Preparation method (Tincture): Take 100 grams of dry ground root of Angelica gigas, pour with 500 milliliters of 40% ethyl alcohol. Infuse in a dark glass container in a cool place at a temperature of 15 to 20°C for 14 days. Shake daily. After completion, strain the infusion, pour into a bottle with a tight lid.

Storage Conditions and Shelf Life (Tincture): Store in a dark tightly closed glass container at a temperature of 5 to 25°C away from light and heat sources. Avoid exposure to EMI. Shelf life — up to 3 years. After opening, use within 60 days.

Oil Infusion — Angelica gigas

Indications (Oil Infusion): Endometriosis, uterine fibroids, dysmenorrhea, osteoarthritis, post-traumatic pain syndrome, chronic prostatitis, neuropathic pain.

Standard Dosage (Oil Infusion): Externally: rub 3 milliliters of oil infusion into the lower abdomen or lower back area once a day for 14 days.

Enhanced Dosage (Oil Infusion): Externally: up to 5 milliliters per application area 2 times a day — for pronounced pain syndrome against the background of endometriosis or uterine fibroids.

Maximum Dosage (Oil Infusion): Externally: up to 8 milliliters per area, no more than 2 times a day, no more than 7 days in a row. Used for intense pelvic pain and neuralgia.

Preventive Dosage (Oil Infusion): Externally: 2 milliliters once every 3 days for women with chronic pelvic pain, in the postoperative period, or for premenstrual pain. Frequency of courses — 10 procedures, repeated every 2 months.

Pediatric Dosage (Oil Infusion): Not recommended for children under 12 years. From 12 years with a body weight of more than 40 kilograms, no more than 1 milliliter once a day can be applied as prescribed by a doctor.

Contraindications (Oil Infusion): Open wounds, pregnancy, individual intolerance to essential components, inflammatory skin diseases. Safety in childhood has not been established.

Side Effects (Oil Infusion): Local irritation, itching, erythema, sensation of heat. With prolonged use, skin peeling is possible.

Adjustment for Patient Body Weight (Oil Infusion): For body weight up to 50 kilograms — use reduced volumes (up to 2 ml per application). For body weight more than 80 kilograms — an increase in volume to 5 ml is possible.

Preparation method (Oil Infusion): Grind 50 grams of dry root of Angelica gigas. Pour with 100 milliliters of organic cold-pressed coconut oil. Keep in a water bath at a temperature of 40–45°C for 4 hours. Cool, strain through gauze, pour into a dark glass container.

Storage Conditions and Shelf Life (Oil Infusion): Store in a tightly closed dark glass bottle at a temperature of 10 to 25°C away from direct light. Shelf life — up to 6 months. After opening, use within 30 days.

Ointment — Angelica gigas

Indications (Ointment): Trigeminal neuralgia, radiculitis, lumbar osteochondrosis, arthralgia, myalgia, chronic prostatitis, neuropathic pain.

Standard Dosage (Ointment): Externally: apply a thin layer 2 times a day to the painful area. Course duration — up to 10 days.

Enhanced Dosage (Ointment): Externally: up to 3 times a day on the area of intense pain, including the projection of plexuses and joints. Course — up to 7 days.

Maximum Dosage (Ointment): Externally: up to 4 times a day for severe forms of neuralgia or radiculitis, course no more than 5 days.

Preventive Dosage (Ointment): Externally: once a day every other day on the lumbar area or cervicothoracic junction in patients with a sedentary lifestyle or chronic osteochondrosis. Course — 14 applications, repeated after 2 months.

Pediatric Dosage (Ointment): From 10 years, locally on a small area, no more than 0.5 grams of ointment once a day. Use should be carried out under adult supervision.

Contraindications (Ointment): Open skin damage, pustular diseases, individual intolerance. No data on use during pregnancy and lactation. Safety in children under 10 years has not been established.

Side Effects (Ointment): Redness of the skin, itching, contact dermatitis. In rare cases — burning sensation.

Adjustment for Patient Body Weight (Ointment): For body weight less than 50 kilograms — reduce the volume of application by 30%. For body weight more than 90 kilograms — an increase in volume by 20% is possible.

Preparation method (Ointment): Take 20 grams of dry extract of Angelica gigas root, dissolve in 10 milliliters of warm coconut oil. Add 60 grams of lanolin and 10 grams of beeswax. Melt in a water bath at a temperature of 60°C with constant stirring. After obtaining a homogeneous mass, cool to 35°C and package in containers.

Storage Conditions and Shelf Life (Ointment): Store in a tightly closed jar in the refrigerator at a temperature of +2 to +8°C. Avoid exposure to light. Shelf life — 3 months. After opening — 30 days.

Cream — Angelica gigas

Indications (Cream): Climacteric syndrome, dry skin in hypoestrogenism, atrophic vaginitis (external use), hyperpigmentation, dermatoses, postmenopausal skin itching.

Standard Dosage (Cream): Externally: apply once a day in the evening to clean dry skin in the area of the lower abdomen, chest, or face. Course — 21 days.

Enhanced Dosage (Cream): Externally: 2 times a day for 14 days for pronounced climacteric symptoms, dry skin, and itching.

Maximum Dosage (Cream): Externally: up to 3 times a day for pronounced itching and dermatoses — no more than 7 days.

Preventive Dosage (Cream): Externally: once a day for 7 days in a row monthly for women over 45 years suffering from dry skin, post-hormonal dermatopathy, and local itching.

Pediatric Dosage (Cream): Use is not recommended in childhood. No data on safety for the skin of children under 14 years have been registered.

Contraindications (Cream): Pregnancy, lactation, individual hypersensitivity. In hormone-dependent tumors, the cream is not used. Childhood is a contraindication.

Side Effects (Cream): Rarely — local hyperemia, itching, allergic reactions. With prolonged use — increased skin sensitivity.

Adjustment for Patient Body Weight (Cream): Dose adjustment is not required. The volume of application is regulated by the area of the lesion.

Preparation method (Cream): Mix 20 grams of Angelica gigas extract with 60 grams of base moisturizing cream (based on shea butter and coconut oil). Add 10 milliliters of lavender flower water and 10 grams of glycerin. Whip until completely homogeneous. The cream is ready for use.

Storage Conditions and Shelf Life (Cream): Store in a glass container with a lid at a temperature of 5 to 15°C. Do not allow heating and exposure to light. Shelf life — 90 days. After opening, use within 21 days.

Serum — Angelica gigas

Indications (Serum): Postmenopausal skin aging, hypoestrogenic changes of the facial skin, chronic skin dehydration, dull complexion, wrinkles, decreased skin elasticity.

Standard Dosage (Serum): Apply once a day in the evening to cleansed skin of the face and neck, 1 milliliter of serum. Course duration — 21 days.

Enhanced Dosage (Serum): 2 times a day — morning and evening, 1 milliliter on the face and neck, for signs of severe age-related skin degradation and hypoestrogenic conditions in women over 50 years. Course — 14 days.

Maximum Dosage (Serum): Up to 3 milliliters per day (1 ml × 3 applications) for pronounced skin thinning and deep wrinkles. Course no more than 10 days.

Preventive Dosage (Serum): 1 milliliter once a day in the evening, in 10-day courses each month. Recommended for women in perimenopause and in post-hormonal reconvalescence.

Pediatric Dosage (Serum): Contraindicated for children under 16 years. Use in adolescents is not recommended. Safety has not been studied.

Contraindications (Serum): Pregnancy, hormone-dependent tumors, hypersensitivity to components. Childhood under 16 years. Lactation.

Side Effects (Serum): Local skin irritation, temporary feeling of tightness, redness. With prolonged use without breaks, sensitization is possible.

Adjustment for Patient Body Weight (Serum): Dose adjustment is not required. The volume of application depends on the area of the skin.

Preparation method (Serum): Take 10 grams of dry extract of Angelica gigas root, dissolve in 60 milliliters of Damascus rose hydrolate. Add 20 milliliters of aloe vera gel and 10 milliliters of jojoba oil. Emulsify until a homogeneous phase is obtained. Pour into a dispenser bottle.

Storage Conditions and Shelf Life (Serum): Store at a temperature of +4 to +10°C in a dark place. Use within 45 days after opening. Shelf life in closed form — 90 days.

Lotion — Angelica gigas

Indications (Lotion): Hyperpigmentation, age-related skin changes, post-acne, seborrheic dermatitis, dull skin tone, tired facial appearance, premenstrual facial edema.

Standard Dosage (Lotion): Apply with a cotton pad once a day in the morning after washing. Volume — 3–4 milliliters on the face and neck.

Enhanced Dosage (Lotion): 2 times a day — morning and evening for pronounced pigmentation, gray skin tone, and premenstrual edema. Course — up to 14 days.

Maximum Dosage (Lotion): Up to 10 milliliters per day on the area of the face, neck, and décolleté. Do not use longer than 7 days in a row at this dose.

Preventive Dosage (Lotion): Once a day every other day, 3 milliliters, course of 14 applications, every 2 months. Suitable for women with age-related pigmentation, as well as patients after prolonged exposure to solar radiation.

Pediatric Dosage (Lotion): Not recommended for children under 14 years. Safety of use in adolescence has not been established.

Contraindications (Lotion): Hypersensitivity to components, individual skin reaction, rosacea in the active stage. Contraindicated during pregnancy and lactation.

Side Effects (Lotion): Dry skin, burning sensation, temporary redness. Rarely — peeling and increased skin sensitivity.

Adjustment for Patient Body Weight (Lotion): Dose adjustment is not required.

Preparation method (Lotion): Dissolve 5 grams of dry extract of Angelica gigas root in 80 milliliters of chamomile hydrolate. Add 10 milliliters of cucumber juice and 5 milliliters of glycerin. Mix until homogeneous, pour into a spray bottle.

Storage Conditions and Shelf Life (Lotion): Store in the refrigerator at a temperature of +2 to +8°C. Shelf life — 30 days. After opening, use within 14 days.

Aqueous Extract — Angelica gigas

Indications (Aqueous Extract): Iron deficiency anemia, chronic hepatitis, climacteric syndrome, postmenopausal psychoemotional disorders, osteoporosis, depression, chronic inflammatory bowel diseases.

Standard Dosage (Aqueous Extract): 15 milliliters 2 times a day, 20 minutes before meals. Course of intake — 21 days followed by a break of at least 10 days.

Enhanced Dosage (Aqueous Extract): 25 milliliters 2 times a day for chronic hepatitis, postmenopausal depression, and osteoporosis. Course — 14 days, repeat no earlier than after 14 days.

Maximum Dosage (Aqueous Extract): 30 milliliters 2 times a day, but no more than 7 days in a row. Used only under medical supervision in conditions of intensive therapy for climacteric syndrome or chronic inflammatory bowel diseases.

Preventive Dosage (Aqueous Extract): 10 milliliters once a day in the morning for 10 days every 2 months. Suitable for perimenopausal women, patients with mild anemia, and during weakness after viral diseases.

Pediatric Dosage (Aqueous Extract): Use is permissible from 12 years with a body weight of more than 40 kilograms, 5 milliliters once a day. Mandatory dilution in warm water is required.

Contraindications (Aqueous Extract): Pregnancy, lactation, severe forms of liver diseases, individual intolerance. Safety for children under 12 years has not been established.

Side Effects (Aqueous Extract): Nausea, increased menstrual bleeding, heartburn. When the dosage is exceeded, dizziness and weakness are possible.

Adjustment for Patient Body Weight (Aqueous Extract): Up to 50 kilograms — reduce the dose by 25%. More than 80 kilograms — increase the dosage to 20%.

Preparation method (Aqueous Extract): Grind 100 grams of dry root of Angelica gigas. Pour with 1000 milliliters of distilled water. Boil in a water bath at a temperature of 90°C for 60 minutes. Cool, filter through a sterile gauze filter. Pour into sterile bottles.

Storage Conditions and Shelf Life (Aqueous Extract): Store in the refrigerator at a temperature of +2 to +8°C in airtight dark containers. Shelf life — up to 14 days. After opening, use within 3 days.

Toxicity and Biosafety of Angelica gigas

Angelica gigas has a high degree of biosafety upon oral and external use at therapeutic doses. According to experimental studies, acute toxicological testing of the root extract of Angelica gigas on laboratory animals showed low toxicity.

The determined LD₅₀ value for the aqueous extract of Angelica gigas per os in mice exceeds 5000 mg/kg body weight, which classifies the substance as practically non-toxic according to the Hodge & Sterner scale. Upon repeated administration at a dose of up to 2000 mg/kg for 14 days, no histopathological changes in internal organs were observed.

The mechanisms of estrogen-like activity described for decursin and decursinol angelate are not accompanied by cytotoxicity against liver cells and intestinal epithelium at therapeutic concentrations. Nevertheless, long-term use at high doses requires monitoring of hormonal levels in women at risk of hyperestrogenism.

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

Pharmacodynamics — Angelica gigas

The pharmacodynamic action of Angelica gigas is associated with the presence of specific coumarins, mainly decursin and decursinol angelate, which have complex modulating activity with respect to a number of biological systems. The main points of application are the nervous, endocrine, immune, and vascular systems, as well as the skin and mucous membranes. In vitro and in vivo studies indicate the ability of these compounds to influence the activity of enzymes involved in the synthesis and inactivation of inflammatory mediators and pain sensitivity, including cyclooxygenases (COX) and lipoxygenases.

Modulation of receptor cascades, including interaction with estrogen receptors, has been confirmed in cell culture and animal model studies. The structure of active substances allows mimicking the action of endogenous hormones without inducing direct tissue proliferation, which forms a selective regulatory effect on hormone-dependent processes. At the same time, the absence of direct cytotoxicity at physiological concentrations is demonstrated.

At the level of the nervous system, a pronounced sedative and anxiolytic potential is observed, mediated through regulation of GABAergic transmission. Active components of Angelica gigas potentiate inhibitory processes in the cortex and hypothalamic-pituitary system, which is accompanied by a decrease in excitation and reactivity in response to stress stimuli.

At the systemic level, antioxidant properties have been established, realized through suppression of lipid peroxidation, stabilization of membrane structures, and enhancement of the activity of endogenous antioxidant enzymes (catalase, superoxide dismutase). This allows reducing oxidative stress and maintaining cellular homeostasis under conditions of inflammation or age-related changes.

Immunotropic activity is manifested in mild modulation of phagocytic function, cytokine production, and stabilization of T-helper activity. The absence of immunosuppression makes Angelica gigas promising for supportive therapy in adaptive response disorders.

An effect on smooth muscles and vascular tone has also been described. Coumarin derivatives of Angelica gigas can reduce vasoconstriction and facilitate local blood flow, partially through antagonism of calcium channels and synthesis of nitric oxide in the endothelium. This provides local myorelaxant and vasodilating action.

Activity against a number of bacterial and fungal agents has been confirmed through disruption of the integrity of the microbial cell membrane. However, antibacterial effects develop only at high concentrations, mainly in vitro, and are not system-forming in the pharmacodynamics of the plant.

Thus, the pharmacodynamic profile of Angelica gigas is determined by the combined effect on endocrine, neurohumoral, and immune mechanisms, with leading effects of sedative, adaptogenic, modulating, and antioxidant nature with predominantly systemic action.

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

Pharmacokinetics — Angelica gigas

The pharmacokinetic characteristics of Angelica gigas have been mainly studied on the model of aqueous and alcoholic extracts containing highly active coumarins, polysaccharides, flavonoids, and volatile components. The main route of administration is oral, as well as transdermal when used in the form of creams, ointments, serums, and oil infusions.

When taken orally, active components, including decursin, undergo absorption in the upper parts of the gastrointestinal tract. Absorption occurs mainly by passive transport, with the participation of microsomal enzymes of the intestinal epithelium. Metabolism begins already at the level of the intestinal wall and continues in the liver, where hydroxylation, methylation, and conjugation with glucuronic acid occur.

Coumarin compounds actively bind to plasma proteins, which facilitates their systemic delivery to target organs. Distribution occurs mainly in tissues with high vascularization: liver, kidneys, endocrine organs, and central nervous system. Accumulation in adipose tissue is limited due to the low lipophilicity of most active metabolites, however, prolonged circulation is possible with chronic intake.

Transdermal preparations (ointment, cream, infusion) penetrate through the epidermis and partially through the sebaceous glands. Bioavailability in this case is limited by the barrier function of the skin, however, the local concentration reaches therapeutic levels in the subcutaneous tissue and dermal capillaries.

Metabolism of active substances is carried out mainly in the liver by the cytochrome P450 system. Final metabolites are excreted by the kidneys with urine and to a lesser extent with bile. For some components, especially water-soluble flavonoids and phenolic acids, rapid excretion without accumulation has been noted.

Components used externally, as a rule, do not penetrate the systemic circulation in significant concentrations. This minimizes the risk of systemic effects with local use, while simultaneously ensuring bioavailability at the site of application.

Thus, the pharmacokinetics of Angelica gigas corresponds to the typical profile of herbal remedies with predominantly hepatic metabolism, oral bioavailability, and predominant renal excretion, with partial participation of bile.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531462/
https://www.tandfonline.com/do...
https://pubmed.ncbi.nlm.nih.gov/22060048/
https://www.sciencedirect.com/science/article/pii/S0378874107001322

Mechanisms of Action and Scientific Rationale — Angelica gigas

The pharmacological action of Angelica gigas is realized through a complex of biochemical mechanisms associated with the main groups of secondary metabolites, including coumarins (decursin, decursinol angelate), polysaccharides, flavonoids, and essential oils. The key molecular targets with which these substances interact include receptors of hormonal regulation (primarily estrogen receptors), enzymes of the inflammatory cascade (cyclooxygenases, lipoxygenases), neurotransmitter systems, and intracellular signaling pathways.

The mechanism of interaction with estrogen receptors (ERα, ERβ) is described as partial agonism with tissue-specific activity. Coumarins of Angelica gigas demonstrate affinity for class I nuclear receptors, initiating transcriptional cascades that regulate the expression of genes associated with proliferation, apoptosis, and cell differentiation. At the same time, no hyperproliferative response is observed in sensitive tissues, which indicates selective activity and the possibility of action within the SERM (Selective Estrogen Receptor Modulator) model.

At the level of mediator systems, decursin and its derivatives inhibit the activity of cyclooxygenase-2 (COX-2) and suppress the synthesis of prostaglandins E2, reducing the pro-inflammatory background. Simultaneously, inhibition of the expression of the transcription factor NF-κB, responsible for the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), is observed. This creates conditions for modulation of the systemic inflammatory response and protection from oxidative stress.

Flavonoid compounds contained in Angelica gigas exhibit antioxidant activity through direct interaction with reactive oxygen species (ROS), as well as through stimulation of the enzymatic activity of superoxide dismutase and catalase. The antioxidant effect is systemic in nature and contributes to the stabilization of membrane structures, improvement of microcirculation, and a decrease in the damaging effect of free radicals on the endothelium and nervous tissue.

The sedative and anxiolytic effect of Angelica gigas is realized partially through activation of GABA receptors in the structures of the central nervous system. Enhancement of inhibitory processes is assumed by increasing the affinity of receptors for endogenous ligands. The effect on dopaminergic and serotonergic systems is less pronounced, but is also noted in a number of publications when analyzing behavioral models.

Additional mechanisms include effects on the MAPK cascade, which is reflected in the modulation of cell proliferation and apoptosis, especially with respect to immune system cells and epithelium. Some components of Angelica gigas demonstrate the ability to inhibit tyrosine kinases and suppress angiogenesis, including through inhibition of VEGF-dependent signals.

At the level of the immune system, the ability of aqueous extracts of the plant to normalize the Th1/Th2 response balance has been described, contributing to a decrease in hyperreactivity and restoration of regulatory functions. A decrease in the expression of adhesion molecules in the endothelium has also been recorded, which may reduce cell infiltration during inflammatory reactions.

Thus, the mechanisms of action of Angelica gigas include receptor, enzyme, and signaling mediation, forming a broad matrix of pharmacological effects confirmed by experimental data.

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

Synergy — Angelica gigas

Synergistic activity of Angelica gigas has been established when combining its extracts with other herbal remedies possessing similar or complementary mechanisms of action. The most pronounced pharmacological synergy has been noted in combination with phytoestrogenic and adaptogenic components, as well as substances with antioxidant and anti-inflammatory properties.

Experimental models show potentiation of antioxidant activity when combining Angelica gigas with Panax ginseng. In this combination, enhanced suppression of free radical oxidation, modulation of SOD and GPx expression, as well as a decrease in TNF-α and IL-6 levels, are observed. This effect is additive and protective in nature, enhancing the neurotropic and endothelioprotective action of both plants.

Additional synergy has been identified when used together with Cimicifuga racemosa, especially with respect to hormone-receptor mechanisms. Both taxa exhibit similar activity with respect to estrogen receptors, however, their combination leads to a more balanced distribution between ERα and ERβ, reducing the risk of stimulation of proliferation in sensitive tissues. This indicates a selective tissue-specific modulating effect.

When combined with Curcuma longa, the anti-inflammatory potential of Angelica gigas is enhanced through co-inhibition of the NF-κB cascade and suppression of the production of pro-inflammatory cytokines. In a study on the RAW264.7 model, it was established that the combined use of extracts reduces the level of nitric oxide and iNOS activity more effectively than each component individually.

Synergy with Withania somnifera has been noted with respect to anti-stress and adaptogenic effects. The combination has a potentiating effect on the regulation of the HPA axis, reducing corticosteroid levels and restoring receptor sensitivity to dopamine and serotonin.

Interaction with antibacterial components (for example, Berberis vulgaris) has also been described, in which Angelica gigas enhances the permeability of the microbial cell membrane and potentiates the activity of alkaloids, allowing a reduction in their concentration without loss of effectiveness.

Thus, Angelica gigas demonstrates predominantly potentiating and modulating synergy, forming systemic, tissue-specific, and cellular interaction with substances of natural origin acting through similar or complementary pharmacological mechanisms.

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

Geography of Use and Traditional Medicine — Angelica gigas

Angelica gigas is traditionally used in the folk and traditional medicine of the Korean Peninsula, including the territory of the modern Republic of Korea and the DPRK, as well as in the northeastern regions of China, especially in the provinces of Jilin and Liaoning. In Korean, the plant is known as "Cham-dang-gui" and is considered an important element of traditional East Asian phytotherapy. In traditional Korean medicine, it is included in female tonic collections, often in combination with other root plants, such as ginseng or astragalus.

Forms of use include aqueous root decoctions, alcohol infusions, steam inhalations, as well as local applications in the form of a paste or wraps. The juice of fresh root in the warm season was used for rubs in folk healing practices. Dried roots were often included in powders and ash compositions mixed with other components.

It is believed that the first documented mentions of Angelica gigas date back to the Joseon Dynasty (1392–1897), where the plant appears in pharmacopoeial records as a component of restorative decoctions, especially for women. In the texts of the Korean medical school of hwachong (traditional herbal medicine), the use of Angelica gigas as a means of harmonizing the life energy "gi" and strengthening the blood is described.

In North Korean practices, Angelica gigas is included in collections intended to maintain the balance between "heat" and "cold" in the body. There, the plant is considered a natural stabilizer of female energy and rhythm, especially in age-related transitional stages. In the traditions of Korean shamans (mu-dan), it could also be used for ritual purposes for purification and protection, however, such information was more often transmitted orally and not always documented.

In Chinese folk tradition, Angelica gigas was used to a limited extent, mainly as a substitute or supplement to Angelica sinensis. Its action was perceived as "warming," and the plant was included in collections used for general strengthening, maintaining strength after childbirth, and during exhaustion.

Non-medical use of Angelica gigas has been recorded in rituals of purifying dwellings in rural areas of Korea, where dried root was hung over the entrance as a protective amulet. It could also be included in fumigations during seasonal rituals of expelling evil spirits. In the folklore of some provinces, the plant was considered a symbol of female vitality and was used in initiation rituals.

In Japan and in Buddhist monasteries of China, this plant practically did not spread, yielding to other species of angelica. In Siberia and among the peoples of Altai, similar use is assigned to other representatives of the genus Angelica.

Thus, Angelica gigas represents a deeply rooted ethnomedical resource of the Korean Peninsula, with many forms of traditional use and symbolic significance in folk culture.