Codonopsis Pilosula (Dangshen Bellflower)

Codonopsis Pilosula (Dangshen Bellflower)

Product Name: Кодонопсис уссурийский, Codonopsis pilosula, Ussurischer Glockenwinden, Campanilla ussuriense, Codonopsis de l'Oussouri, كودونوبسيس بيلوسولا, โคโดโนพซิส พิโลซูลา, Kodonopsis pilosula, Кодонопсис пилосула, Kodonopsis pilosula, Кодонопсис пилосула, Кодонопсис пилосула, Codonopsis pilosula, קודונופסיס פילוסולה

Synonyms: кодонопсис волосистый, колокольчик китайский, колокольчик дальневосточный, poor man's ginseng, bastard ginseng, false ginseng, dangshen bellflower, bonnet bellflower, falscher Ginseng, Codonopsis, ginseng de los pobres, ginseng du pauvre, جينسنغ الفقراء, โสมปลอม, โสมคนจน

Parts Used: root, aerial part, leaves, stem, flowers, seeds.

Main Indications for Use of Codonopsis pilosula: Chronic gastritis, gastric ulcer, duodenitis, iron deficiency anemia, hypoglycemia, chronic fatigue, hypotension, asthenic syndrome, immunodeficiency states, recovery after infectious diseases, malabsorption syndrome, cachexia, oncological diseases (as part of supportive therapy), microcirculation disorders, age-related sarcopenia, neuroendocrine disorders, Alzheimer's disease (early stage), metabolic syndrome, hypothyroidism.

Use of Codonopsis pilosula in mixtures and complexes: Chronic bronchitis, obstructive pulmonary disease, osteoarthritis, osteoporosis, chronic heart failure, liver cirrhosis, viral hepatitis B, type 2 diabetes mellitus, pancreatitis, neuropathic pruritus, post-COVID syndrome, sleep disorders, anxiety disorders, climacteric syndrome, hypertension.

Pharmacological Properties of Codonopsis pilosula: adaptogenic, immunomodulatory, anti-inflammatory, antioxidant, hypoglycemic, gastroprotective, hepatoprotective, nootropic, antidepressant, neuroprotective, hematopoietic, cardiotonic, antimicrobial, sedative, anxiolytic, cytoprotective, anti-aging, vasoregulatory, oncoprotective, anti-anemic, metabolic.

Dosage of Pharmaceutical Forms — Codonopsis pilosula

Powder — Codonopsis pilosula

Indications (Powder): Chronic gastritis, duodenitis, iron deficiency anemia, hypoglycemia, chronic fatigue, immunodeficiency states, malabsorption syndrome, cachexia, age-related sarcopenia, neuroendocrine disorders.

Standard Dosage (Powder): 3 grams of powder once a day in the morning, 30 minutes before meals, with warm water.

Enhanced Dosage (Powder): 3 grams of powder twice a day (morning and noon), for chronic fatigue, immunodeficiency states, malabsorption syndrome, cachexia.

Maximum Dosage (Powder): 5 grams of powder twice a day, for 7–10 days, for severe sarcopenia, cachexia, severe forms of anemia.

Preventive Dosage (Powder): 1 gram of powder once a day in the morning, in a course of 30 days, repeated 2–3 times a year. Recommended for patients with chronic forms of gastritis, anemia, hypoglycemia, elderly patients, and persons with physical exhaustion.

Pediatric Dosage (Powder): For children from 6 years of age and weighing more than 20 kg — 0.5–1 gram once a day in the morning, with warm water. Not recommended for children under 6 years due to lack of studies.

Contraindications (Powder): Individual intolerance, tendency to hyperglycemia, active phase of infectious diseases with elevated body temperature. Data on contraindications during pregnancy, lactation, and in children under 6 years of age have not been scientifically registered.

Side Effects (Powder): Registered: dyspepsia, bloating, drowsiness in case of overdose.

Adjustment for Patient Body Weight: For patients weighing below 60 kg — reduce the dosage by 20%. For body weight above 90 kg — increase the dosage by 20%.

Preparation Method (Powder): Raw material: roots of Codonopsis pilosula — 100 grams. Wash the roots under running water, cut into thin slices, dry at a temperature of 40–50 °C in the shade with good ventilation until stable brittleness. Grind into powder using a ceramic mortar or a stainless steel mill. Sift through a 0.5 mm mesh sieve. Store in an airtight glass container.

Storage Conditions and Shelf Life (Powder): Store in a tightly closed glass jar at a temperature from +10 °C to +25 °C, in a dark, dry place shielded from electromagnetic radiation. Shelf life — up to 18 months. After opening the package, use within 60 days.

Dry Extract — Codonopsis pilosula

Indications (Dry Extract): Iron deficiency anemia, hypoglycemia, chronic fatigue, immunodeficiency states, age-related sarcopenia, metabolic syndrome, neuroendocrine disorders, hypotension.

Standard Dosage (Dry Extract): 500 milligrams of 5:1 extract once a day in the morning, 30 minutes before meals.

Enhanced Dosage (Dry Extract): 500 milligrams twice a day (morning and noon), for severe asthenia, sarcopenia, immunodeficiency states.

Maximum Dosage (Dry Extract): 1000 milligrams twice a day, for 5–7 days, for severe hypotension and cachexia.

Preventive Dosage (Dry Extract): 250 milligrams once a day in the morning, in a course of 30 days. Suitable for patients with hypoglycemia, elderly people, postmenopausal women, and those with neuroendocrine disorders.

Pediatric Dosage (Dry Extract): For children from 8 years of age weighing from 25 kg — 150 milligrams once a day. Safety in children under 8 years has not been established.

Contraindications (Dry Extract): Individual intolerance, hyperglycemia, active tumors of the gastrointestinal tract. Data on contraindications during pregnancy, lactation, and in children under 8 years of age have not been scientifically registered.

Side Effects (Dry Extract): Registered: headache, increased appetite, tachycardia in case of overdose.

Adjustment for Patient Body Weight: For body weight less than 60 kg — reduce the dosage by 20%. For body weight more than 90 kg — increase the dosage by 20%.

Preparation Method (Dry Extract): Ingredients: codonopsis root — 500 grams, purified water — 2000 milliliters. Boil at a temperature of +90 °C for 3 hours. Filter through thick gauze. Evaporate the obtained extract to a viscous mass. Dry in a vacuum dryer at a temperature not exceeding +50 °C to a powder state. From 500 grams of raw material, about 100 grams of 5:1 extract are obtained.

Storage Conditions and Shelf Life (Dry Extract): Store in a tightly sealed container, in a cool and dry place at a temperature from +10 °C to +25 °C. Avoid exposure to direct light and electromagnetic radiation. Shelf life — up to 24 months. After opening, use within 60 days.

Alcohol-Based Tincture — Codonopsis pilosula

Indications (Tincture): Chronic gastritis, iron deficiency anemia, hypotension, immunodeficiency states, neuroendocrine disorders, asthenic syndrome, hypoglycemia.

Standard Dosage (Tincture): 20 drops of tincture in 40% ethanol (1:5) three times a day 20 minutes before meals, diluted in 50 ml of water.

Enhanced Dosage (Tincture): 30 drops three times a day for severe fatigue, anemia, hypotension, exhaustion syndromes, and recovery after severe infections.

Maximum Dosage (Tincture): Up to 40 drops three times a day for no more than 7 days for hypotension, cachexia, severe iron deficiency anemia.

Preventive Dosage (Tincture): 15 drops once a day in the morning, diluted in water. Used for chronic fatigue, hypotension, anemia in elderly patients, as well as for immunodeficiency in frequently ill adults, in courses of 21 days twice a year.

Pediatric Dosage (Tincture): Not recommended for children under 14 years due to ethanol content. Data on safety of use in pediatrics are absent.

Contraindications (Tincture): Alcoholism, epilepsy, liver diseases, active infectious diseases with fever. Data on contraindications during pregnancy, lactation, and in children under 14 years of age have not been scientifically registered.

Side Effects (Tincture): Registered: headache, tachycardia, irritability, insomnia in case of overdose.

Adjustment for Patient Body Weight: Body weight <60 kg — reduce the dose by 20%. Body weight >90 kg — increase the dose by 20%.

Preparation Method (Tincture): Ingredients: dry codonopsis root — 100 grams, 40% ethanol — 500 milliliters. Grind the root to a size of 2–4 mm. Place in a glass container, fill with ethanol. Infuse for 14 days at a temperature from +18 °C to +22 °C in the dark, shaking periodically. Filter through gauze. Store in a sealed dark container.

Storage Conditions and Shelf Life (Tincture): Store in a cool, dark place at a temperature from +10 °C to +25 °C, away from electromagnetic sources. Shelf life — 24 months. After opening, use within 60 days.

Oil Infusion — Codonopsis pilosula

Indications (Oil Infusion): Dry skin, neurodermatitis, skin hypotrophy, age-related skin changes, iron deficiency anemia (as part of applications in Ayurvedic massage), chronic fatigue (when applied to adrenal projections).

Standard Dosage (Oil Infusion): Topically — 2 ml per application area, once or twice a day. Applications on the skin for no more than 30 minutes for sensitive skin.

Enhanced Dosage (Oil Infusion): 3–5 ml per application zone for severe dry skin, hypotrophy, age-related atrophy, in Ayurvedic massage programs.

Maximum Dosage (Oil Infusion): Up to 10 ml for the whole body as part of oil massages no more than 2 times a week. It is recommended to keep on the skin for no more than 60 minutes.

Preventive Dosage (Oil Infusion): 1 ml per local application area (hands, neck, face) 3 times a week. Used in persons with chronic fatigue, elderly patients, for age-related skin, and while taking medications that cause dry skin.

Pediatric Dosage (Oil Infusion): For children from 3 years old — spot application up to 0.5 ml on elbow creases and soles of the feet no more than 2 times a week. Use only after a test application on a small area of skin.

Contraindications (Oil Infusion): Individual intolerance, acute pustular skin diseases, weeping dermatoses. Data on contraindications during pregnancy, lactation, and in children under 3 years of age have not been scientifically registered.

Side Effects (Oil Infusion): Registered: itching, redness, allergic reaction in the application area in case of hypersensitivity.

Adjustment for Patient Body Weight: Not required, as it is used externally. However, with body weight less than 20 kg (children) — reduce the application area.

Preparation Method (Oil Infusion): Ingredients: codonopsis root powder — 10 grams, cold-pressed coconut oil — 90 grams. Mix the powder and oil in a glass jar, close tightly. Infuse in a water bath at a temperature of +50 °C for 4 hours, stirring occasionally. Cool, strain through a nylon filter. Store in a sealed bottle.

Storage Conditions and Shelf Life (Oil Infusion): Store in a dark, cool place at a temperature from +5 °C to +18 °C. Avoid contact with sunlight and heating appliances. Shelf life — 6 months. After opening, use within 45 days.

Ointment — Codonopsis pilosula

Indications (Ointment): Neurodermatitis, eczema, dry dermatitis, age-related skin atrophy, skin hypotrophy, skin pruritus in neuroendocrine disorders, local microcirculation deficiency.

Standard Dosage (Ointment): Topically — apply in a thin layer 1–2 times a day to the affected skin areas. Duration of one course — 14 days.

Enhanced Dosage (Ointment): Apply up to 3 times a day for 10 days for severe forms of eczema, skin atrophy, neurodermatitis.

Maximum Dosage (Ointment): Apply 4 times a day in a thin layer, no more than 20 grams of ointment per day, for severe skin pruritus and atrophy. Use no longer than 7 days consecutively.

Preventive Dosage (Ointment): Apply once a day in the evening to areas prone to dryness (elbows, shins, hands). Recommended for elderly patients, for dry skin syndrome, in climatic conditions with low humidity. Course — 10 days per month.

Pediatric Dosage (Ointment): For children from 5 years old — spot application once a day in a minimal amount to limited skin areas (up to 2% of body surface area). Use no longer than 5 days consecutively.

Contraindications (Ointment): Individual intolerance, acute pustular rashes, weeping dermatoses, skin tuberculosis, neoplasms in the application area. Data on contraindications during pregnancy, lactation, and in children under 5 years of age have not been scientifically registered.

Side Effects (Ointment): Registered: contact dermatitis, itching, burning sensation, local erythema in case of hypersensitivity.

Adjustment for Patient Body Weight: For patients with body weight <60 kg — no more than 10 grams of ointment per day. For body weight >90 kg — it is permissible to use up to 20 grams per day for extensive lesions.

Preparation Method (Ointment): Ingredients: codonopsis root powder — 10 grams, coconut oil — 60 grams, beeswax — 30 grams. Melt the wax and oil in a water bath at a temperature of +60 °C. Add codonopsis powder, mix thoroughly, keep on low heat for 30 minutes, stirring occasionally. Remove from heat, cool to +40 °C, and filter through sterile gauze. Pour into sterile jars.

Storage Conditions and Shelf Life (Ointment): Store in a tightly closed dark glass container at a temperature from +5 °C to +15 °C. Avoid exposure to direct light, moisture, and EMI. Shelf life — 6 months. After opening, use within 30 days.

Cream — Codonopsis pilosula

Indications (Cream): Dry skin, age-related changes of facial and hand skin, skin hypotrophy, decreased elasticity and tone, slowed regeneration, microvascular disorders in the epidermis.

Standard Dosage (Cream): Apply 1–2 times a day in a thin layer to clean skin of the face, neck, and hands. Recommended volume — 1 ml per application.

Enhanced Dosage (Cream): Apply up to 3 times a day, including evening application with massage, for severe dryness, age-related flaccidity, post-stress skin changes.

Maximum Dosage (Cream): Up to 3 ml per application on extensive areas of the face, neck, and décolleté area, no more than 3 times a day for 7 days.

Preventive Dosage (Cream): Apply once a day before bedtime in a course of 30 days. Suitable for women over 40, patients with early signs of skin aging, during climatic and hormonal changes.

Pediatric Dosage (Cream): Not recommended for use in children under 12 years. Safety of use has not been established.

Contraindications (Cream): Individual intolerance to components, acute inflammatory processes on the skin, weeping rashes. Data on contraindications during pregnancy, lactation, and in children under 12 years of age have not been scientifically registered.

Side Effects (Cream): Registered: redness, mild burning when applied to damaged skin, allergic contact dermatitis.

Adjustment for Patient Body Weight: Not required, adjustment is made according to the application area.

Preparation Method (Cream): Ingredients: codonopsis extract 5:1 — 2 grams, coconut oil — 40 grams, purified water — 50 grams, emulsifier lecithin — 8 grams. Heat the oil and water phases separately to +60 °C. Combine with constant stirring, add codonopsis extract, continue stirring until thickening and cooling to +30 °C. Pour into sterile bottles.

Storage Conditions and Shelf Life (Cream): Store in a refrigerator at a temperature from +4 °C to +10 °C, in an opaque, sealed package. Shelf life — 3 months. After opening, use within 30 days.

Serum — Codonopsis pilosula

Indications (Serum): Age-related changes of facial skin, decreased elasticity and tone, fine wrinkles, skin dehydration, skin hypotrophy, microvascular disorders, post-stress skin aging.

Standard Dosage (Serum): Apply 2–3 drops to the face and neck once a day, in the evening, on cleansed skin, before applying cream.

Enhanced Dosage (Serum): Apply 2 times a day — morning and evening — 3–4 drops to the face, neck, and décolleté area for severe dehydration and in intensive lifting programs.

Maximum Dosage (Serum): Up to 5 drops 3 times a day for the treatment of age-related changes, photoaging, and preparation for cosmetic procedures. Course — no more than 10 days consecutively.

Preventive Dosage (Serum): 1–2 drops once a day, every other day, in the evening. Use in women and men over 35 years with early signs of loss of skin elasticity. Course — 21 days.

Pediatric Dosage (Serum): Not used in children. Data on safety of use in pediatrics are absent.

Contraindications (Serum): Individual intolerance to components, skin hyperreactivity, acute dermatological conditions. Data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Serum): Registered: redness, burning, contact dermatitis in case of individual hypersensitivity.

Adjustment for Patient Body Weight: Not required, dosage is selected according to skin area and sensitivity.

Preparation Method (Serum): Ingredients per 100 grams: codonopsis extract 5:1 — 3 grams, 1% hyaluronic acid — 10 grams, vegetable glycerin — 10 grams, purified water — 77 grams. Combine the extract with water and glycerin, mix thoroughly until dissolved. Add hyaluronic acid. Homogenize for 10 minutes. Pour into sterile dropper bottles.

Storage Conditions and Shelf Life (Serum): Store at a temperature from +4 °C to +10 °C, in a sealed package made of opaque glass. Avoid sunlight and EMI exposure. Shelf life — up to 2 months. After opening, use within 21 days.

Lotion — Codonopsis pilosula

Indications (Lotion): Dry and sensitive skin, neurodermatitis, restoration of the skin barrier, dull complexion, post-stress changes, microvascular disorders.

Standard Dosage (Lotion): Apply with a cotton pad — 3–5 ml of lotion to cleansed skin 1–2 times a day, preferably in the evening.

Enhanced Dosage (Lotion): 5 ml 2 times a day — morning and evening, for severe dryness, skin sensitivity, during recovery after stress and inflammation.

Maximum Dosage (Lotion): Up to 10 ml 3 times a day for 5 days in an intensive skin regeneration program, in complexes with cosmetic procedures.

Preventive Dosage (Lotion): Apply once a day 2–3 times a week, in courses of 14 days. Recommended for persons over 35 years old working in conditions of dry air or emotional stress.

Pediatric Dosage (Lotion): Not recommended for children under 12 years. For adolescents over 12 years — 1–2 ml on the face no more than once a day if prone to dry skin.

Contraindications (Lotion): Individual intolerance, acute skin inflammations. Data on contraindications during pregnancy and lactation have not been registered.

Side Effects (Lotion): Registered: irritation, feeling of skin tightness, allergic reaction in case of hypersensitivity.

Adjustment for Patient Body Weight: Not required. The volume is determined by the application area.

Preparation Method (Lotion): Ingredients per 100 ml: codonopsis extract (water-alcohol 1:5) — 10 ml, purified water — 85 ml, vegetable glycerin — 5 ml. Mix all components, homogenize thoroughly, filter through a 0.45 µm membrane. Pour into sterile plastic or glass bottles with a spray or dispenser.

Storage Conditions and Shelf Life (Lotion): Store at a temperature from +4 °C to +15 °C, in a light-protected package. Shelf life — up to 90 days. After opening, use within 30 days.

Cosmetic Mask — Codonopsis pilosula

Indications (Cosmetic Mask): Age-related skin changes, decreased elasticity and tone, skin dehydration, dull complexion, stress-induced aging, delayed regeneration, skin hypotrophy, microvascular disorders.

Standard Dosage (Cosmetic Mask): One mask (10–12 grams of mixture) on the face, applied for 15–20 minutes 2 times a week.

Enhanced Dosage (Cosmetic Mask): Mask daily in the evenings for 5–7 days in intensive care programs for severe skin fatigue, age-related flaccidity, photoaging.

Maximum Dosage (Cosmetic Mask): One mask per day for up to 10 days consecutively, followed by a break of 14 days. Use no more than 15 grams per procedure.

Preventive Dosage (Cosmetic Mask): Apply once a week in the evening, in courses of 4 weeks. Recommended for women over 35 years, with decreased skin turgor, impaired water balance, chronic stress, and exposure to urban air.

Pediatric Dosage (Cosmetic Mask): Not recommended for children under 14 years. Safety of use in adolescents has not been studied.

Contraindications (Cosmetic Mask): Individual intolerance, acute inflammatory processes of the skin, open wounds, pustular rashes. Data on contraindications during pregnancy and lactation have not been registered.

Side Effects (Cosmetic Mask): Registered: tingling sensation, hyperemia, local irritation in case of individual intolerance.

Adjustment for Patient Body Weight: Not required. Correction is made according to the application area and skin sensitivity.

Preparation Method (Cosmetic Mask): Ingredients per 100 grams: codonopsis root powder — 10 grams, white cosmetic clay — 60 grams, aloe vera gel — 10 grams, lavender hydrolate — 20 milliliters. Mix dry components, gradually add hydrolate and gel, mix until a homogeneous mass is obtained. If necessary, adjust the consistency by adding water. Put into sealed jars.

Storage Conditions and Shelf Life (Cosmetic Mask): Store in a refrigerator at a temperature from +4 °C to +10 °C, in a tightly closed dark glass jar. Shelf life — 30 days. After opening, use within 7 days.

Toxicity and Biosafety of Codonopsis pilosula

Studies on the toxicological profile of Codonopsis pilosula show extremely low toxicity and good tolerability even with prolonged use. In animal experiments, it was established that codonopsis root extract does not cause lethal outcomes even at high doses.

Acute toxicological study (acute oral toxicity) in mice showed that the LD₅₀ value of Codonopsis pilosula extract exceeds 18 g/kg body weight when administered orally. This indicates extremely low acute toxicity of the substance. In chronic studies (28-day and 90-day administration), no statistically significant pathological changes were found in the functions of the liver, kidneys, bone marrow, and cardiovascular system.

Thus, Codonopsis pilosula can be considered a pharmacologically safe drug with a high toxicity threshold and good tolerability at standard and therapeutic dosages.

Reference: https://pubmed.ncbi.nlm.nih.gov/26498634/

Pharmacodynamics of Codonopsis pilosula

Codonopsis pilosula is an adaptogenic and metabolically active plant, rich in heterogeneous groups of substances, including polysaccharides, phenolic compounds, triterpene saponins, and phytosterins. These compounds influence a wide range of physiological systems and support the homeostatic activity of the body through systemic and local levels of action.

The pharmacodynamic effect of codonopsis is realized primarily through immunomodulatory influence. Water-soluble polysaccharides activate innate and adaptive elements of the immune system, increasing the functional activity of macrophages, enhancing T-lymphocyte proliferation, and inducing the release of interleukins and interferons. Modulation of the cytokine response is accompanied by improved cellular communication and normalization of inflammatory cascades.

Codonopsis has a pronounced anti-inflammatory effect mediated by inhibition of the production of pro-inflammatory mediators, such as prostaglandins, TNF-α, and IL-6, through effects on the NF-κB and MAPK signaling pathways. This effect is manifested both systemically and locally when using external forms, especially regarding skin and mucous tissues.

On the nervous system, the plant has a sedative-adaptogenic effect. Studies demonstrate that saponins and phenolic fractions of codonopsis affect the level of monoamines (primarily serotonin and dopamine), as well as the regulation of GABA-ergic transmission, which confirms its neuromodulatory and anxiolytic potential. Codonopsis also helps maintain cognitive activity through improved microcirculation and antioxidant protection of neurons.

The endocrine system is another pharmacological target. Codonopsis affects the hypothalamus-pituitary-adrenal axis, contributing to the stabilization of cortisol-dependent reactions and reducing stress-induced disorders. A potential effect on glucose metabolism, lipids, and functional activity of the thyroid gland is also observed, through mediated regulation of hormonal receptors and transport proteins.

Regarding the cardiovascular system, codonopsis has a vasoregulatory effect, contributing to the normalization of vascular smooth muscle tone and improvement of blood rheological properties. Polysaccharide components additionally stabilize capillary permeability.

Pharmacodynamic effects are realized both systemically (with oral and parenteral use) and locally (in the form of ointments, creams, serums), covering such target systems as skin, nervous, immune, endocrine, and digestive systems. It is believed that the key molecular targets of action include interleukin receptors, adrenoreceptors, antioxidant defense enzymes (catalase, superoxide dismutase), NF-κB signaling proteins, and regulatory elements of the hypothalamic-pituitary axis.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233699/
https://www.sciencedirect.com/science/article/pii/S0378874110004814
https://pubmed.ncbi.nlm.nih.gov/31675799/
https://www.tandfonline.com/do...

Pharmacokinetics of Codonopsis pilosula

The pharmacokinetics of the biologically active components of Codonopsis pilosula is characterized by variability due to the route of administration and the chemical nature of the compounds. With oral administration, the main routes of absorption are active and passive transport in the proximal parts of the small intestine. Polysaccharides have low intestinal permeability, but biologically significant effects are achieved through their interaction with the intestinal microflora, stimulating the formation of short-chain fatty acids and secondary immune mediators.

Triterpene saponins and phenolic compounds undergo enterohepatic circulation, partial oxidation, and methylation in the liver with the participation of microsomal enzymes (primarily cytochrome P450). Some glycoside fractions are hydrolyzed already at the level of the gastrointestinal mucosa under the action of intestinal microbiota enzymes, which affects their pharmacological activity and bioavailability.

The distribution of active components is predominantly systemic, with tropism for organs providing detoxification, immune, and neuroendocrine functions: the liver, spleen, adrenal glands, lymph nodes, and brain. There is limited penetration of individual flavonoid structures through the blood-brain barrier, which may determine the central sedative and nootropic effect.

With transdermal administration (in the form of ointments, creams, serums), bioavailability depends on the lipophilicity of the components and the presence of transport emulsifiers. Saponins and small phenols show the ability to penetrate into the deep layers of the dermis, exerting systemic and local effects. Penetration is enhanced when using fatty bases, such as coconut oil or shea butter, and when warming the application area.

The metabolism of most codonopsis components occurs in the liver with subsequent conjugation and excretion. Excretion is carried out primarily by the kidneys (water-soluble fractions and their metabolites) and through bile (lipophilic and high-molecular compounds). A certain proportion of substances can be excreted with sweat and through the skin, especially with local use.

Data on cumulation are limited, but long-term use in moderate doses does not lead to the accumulation of toxic metabolites, as confirmed by chronic toxicity studies. Interaction with the microflora of the small and large intestines is important for pharmacological activity, particularly regarding immuno- and neurotropic effects.

References:
https://www.sciencedirect.com/science/article/pii/S0378874116301736
https://pubmed.ncbi.nlm.nih.gov/23976948/
https://www.tandfonline.com/do...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073419/

Mechanisms of Action and Scientific Rationale of Codonopsis pilosula

The pharmacological action of Codonopsis pilosula is realized through a combination of molecular mechanisms determined by the active components of the plant, among which polysaccharides, triterpene saponins, phenolic compounds, and sterols are considered leading. In vitro and in vivo studies have confirmed the participation of these substances in the modulation of key signaling cascades, activity of receptor systems, and enzyme pathways.

Polysaccharide fractions of codonopsis are powerful biologically active modulators of the immune system. They stimulate macrophage activity, enhance the expression of cytokines such as IL-1β, IL-6, and TNF-α, and activate the TLR4/NF-κB pathway, promoting the initiation of the innate immune response. Activation of MAPK signaling, including ERK1/2 and p38, is also noted, leading to increased production of inflammatory mediators and improved cellular communication. Such effects are explained by the highly branched structure of polysaccharides, capable of effectively binding to surface receptors of immunocompetent cells.

Triterpene saponins of codonopsis affect the activity of glucocorticoid receptors, which is manifested in the modulation of the stress response and regulation of systemic anti-inflammatory activity. They also inhibit the enzyme complexes cyclooxygenase-2 (COX-2) and lipoxygenase (5-LOX), limiting the synthesis of pro-inflammatory prostaglandins and leukotrienes. This confirms the participation of saponins in the suppression of inflammatory cascades at the mediator level.

Phenolic compounds of codonopsis provide pronounced antioxidant activity, due to the direct neutralization of reactive oxygen species and increased activity of antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). This mechanism may be complemented by the activation of the Nrf2 signaling pathway, responsible for the transcription of antioxidant defense genes.

Additionally, saponins and polysaccharides of codonopsis demonstrate regulation of cellular metabolic activity, including through the activation of AMPK and the insulin-dependent PI3K/Akt pathway, which may indirectly affect energy metabolism. An effect on PPARγ receptors, responsible for lipid homeostasis and insulin sensitivity, has also been identified.

The neurotropic effects of codonopsis are explained by the ability of its components to modulate neurotransmitter levels, including serotonin, dopamine, and GABA, as well as through effects on GABA-A and 5-HT1A receptors. These mechanisms partially provide the sedative, anxiolytic, and nootropic properties of the plant.

At the systemic level, Codonopsis pilosula demonstrates effects on endothelial function, improving microcirculation by increasing eNOS expression and nitric oxide (NO) synthesis, and also modulates platelet activation and vascular tone.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332473/
https://www.sciencedirect.com/science/article/pii/S0378874116301736
https://pubmed.ncbi.nlm.nih.gov/32451397/
https://pubmed.ncbi.nlm.nih.gov/33986883/

Synergy of Codonopsis pilosula

In vitro and in vivo studies confirm the pharmacological synergy of Codonopsis pilosula with a number of other plant and natural compounds, manifested in the enhancement of immunomodulatory, anti-inflammatory, antioxidant, and neuroprotective effects. The basis of the interaction is made up of additive and potentiating effects due to the similarity or complementarity of biochemical targets.

When combined with astragalus root (Astragalus membranaceus), a synergistic enhancement of cytokine production, activation of T- and B-lymphocytes, and increased NK-cell activity are observed, which is due to the combined modulation of the TLR4/NF-κB and MAPK signaling cascades. This effect is realized through the polysaccharide complexes of both plants, which have a similar spatial configuration and affinity for innate immunity receptors.

Pharmacological interaction with Panax ginseng is manifested in the potentiation of adaptogenic and anti-asthenic effects, which is explained by the combined influence of saponins of both taxa on the receptors of the hypothalamic-pituitary axis and glucocorticoid synthesis. It was found that the combined use of codonopsis and ginseng leads to an increase in the expression of glucocorticoid receptors and an increase in resistance to stress effects in experimental animals.

Synergy with Glycyrrhiza glabra is realized through combined antioxidant and anti-inflammatory activity. Liquiritigenin contained in licorice and polysaccharides of codonopsis modulate COX-2, LOX, and NF-κB pathways, and also complement each other in reducing oxidative stress.

When combined with flavonoid-containing taxa (e.g., Scutellaria baicalensis), mutual enhancement of antioxidant activity and neuroprotective effect is observed. This is due to the activation of the common Nrf2/ARE signaling cascade, as well as the combined inhibition of apoptosis in neuronal cultures.

Combined use with vitamin C (ascorbic acid) demonstrates a protective effect on macrophage cells and epithelium, associated with the restoration of antioxidant balance and stabilization of cell membranes.

Thus, Codonopsis pilosula is an effective synergistic component in phytocomplexes acting at the level of the immune, endocrine, nervous, and vascular systems through effects on common molecular targets, mediators, and receptor cascades.

References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332473/
https://www.sciencedirect.com/science/article/abs/pii/S0378874107003483
https://pubmed.ncbi.nlm.nih.gov/28913875/
https://www.sciencedirect.com/science/article/pii/S037887411730508X

Geography of Use and Traditional Medicine of Codonopsis pilosula

Codonopsis pilosula has wide ethnomedical and cultural significance in a number of Asian countries, mainly in East Asia. Traditionally used in Chinese, Korean, Tibetan, and Mongolian medical schools, as well as in some folk practices of southern Siberia and Primorye.

The most solid and systematic tradition of using Codonopsis pilosula is represented by Chinese medicine, where the plant is known as "dang shen" and occupies an important place as a mild adaptogen and restorative agent. The root of the plant is used in dried form, as part of complex collections, and in the form of alcohol infusions. Decoctions based on the root were used to strengthen the body, recover from physical and mental overload, improve vital energy ("qi"), and as a tonic for loss of strength. Particular importance is attached to its use in the form of decoctions in combination with astragalus root, angelica, and ginseng.

In Tibetan medicine, codonopsis is considered a mild stimulator of vital energy and was included in remedies for strengthening central and peripheral energy ("lung" and "pho").

In the ritual practice of the peoples of Yunnan and Inner Mongolia, dried codonopsis root was sometimes used as a smoking agent during rituals of cleansing space and body. It was believed that the smoke of the plant drives away weakness and restores vitality.

In Korea, codonopsis root was used in the form of boiling in rice porridge or added to medicinal soups used during periods of recovery after illness or childbirth.

Among the ethnic groups of Heilongjiang and Primorsky Krai, it was used as a tonic plant in the form of infusions and ground raw materials mixed with honey.

The first recorded mention of the plant for medicinal purposes can be attributed to the VIII–IX centuries, when it was included in the pharmacopoeial scrolls of the Tang Dynasty. In the "Ben Cao Gang Mu" (pharmacopoeia of the Ming era, XVI century), it is mentioned as one of the substitutes for expensive ginseng. Over the centuries, codonopsis was considered the "herb for the poor" with strength close to the "king of herbs" — ginseng, and was highly valued in peasant families of China, Mongolia, and Korea.

In the culture of the peoples of East Asia, Codonopsis pilosula was often perceived as a plant of strength and recovery, possessing the ability to strengthen spirit and body. In some regions, it was hung over the door in bundles as a symbol of prosperity and longevity. In ancestral veneration rituals, it was used as a ritual offering, especially among the older members of the clan.

Thus, codonopsis has an extensive geography of use, high cultural significance, and a deep history of use in Asian and Eurasian ethnomedical traditions.