Withania somnifera (Ashwagandha / Indian Ginseng)

Withania somnifera (Ashwagandha / Indian Ginseng)

Product Name: Витания снотворная, Withania somnifera, Schlafbeere, Ashwagandha, Ashwagandha, أشواغاندا, เพรียงอินเดีย, Ashvaganda, Уйкучон витания, Aşvaganda, Ашавганда, Indijos vitanija, Indijas vitānija, Вітанія снотворна, Aşvaganda, אשווגנדה

Synonyms: Ашваганда, зимняя вишня, индийский женьшень; Ashwagandha, Indian ginseng, winter cherry; Schlafbeere, Indischer Ginseng; ashwagandha, cereza de invierno, ginseng indio; ashwagandha, cerise d’hiver, ginseng indien; أشواغاندا، كرز الشتاء، الجنسنغ الهندي; อัศวกันดา, เชอร์รีฤดูหนาว, โสมอินเดีย

Used Parts: roots, leaves, berries, root.

Main Indications for Use of Withania somnifera: Obsessive-compulsive disorder, generalized anxiety disorder, depressive disorder, adjustment disorder, sleep disorders, asthenic syndrome, cognitive disorders in neurodegenerative diseases, androgen deficiency, oligoasthenozoospermia, stress-induced hyperglycemia, type 2 diabetes mellitus, obesity, metabolic syndrome, subclinical hypothyroidism, chronic fatigue syndrome, idiopathic arterial hypertension, immunodeficiency states, benign prostatic hyperplasia.

Use of Withania somnifera in Mixtures and Complexes: Hyperthyroidism, hypercortisolism, hypertensive crisis, anxious depression with psychotic symptoms, schizoaffective disorder, Alzheimer's disease, senile dementia, malignant tumors, viral hepatitis, chronic obstructive pulmonary disease, autoimmune thyroidopathies, multiple sclerosis, psoriasis, vitiligo.

Pharmacological Properties of Withania somnifera: adaptogenic, nootropic, anxiolytic, antidepressant, neuroprotective, anticonvulsant, antioxidant, anti-inflammatory, hepatoprotective, immunomodulating, antiandrogenic, analgesic, hypoglycemic, hypolipidemic, antiproliferative, antipsychotic, thyrotropic, antiplasmodial, cytoprotective, cardiotonic, sedative, antimutagenic, oncoprotective, anti-stress.

Dosage of Pharmaceutical Forms — Withania somnifera

Powder — Withania somnifera

Indications (Powder): Obsessive-compulsive disorder, generalized anxiety disorder, depressive disorder, adjustment disorder, sleep disorders, asthenic syndrome, androgen deficiency, oligoasthenozoospermia, stress-induced hyperglycemia, type 2 diabetes mellitus, obesity, metabolic syndrome, subclinical hypothyroidism, chronic fatigue syndrome, idiopathic arterial hypertension, immunodeficiency states.

Standard Dosage (Powder): 3 to 5 grams of powder per day, divided into two doses (morning and evening) on an empty stomach or 30 minutes before meals, with warm water.

Enhanced Dosage (Powder): Up to 7 grams of powder per day in two to three doses. Used for chronic sleep disorders, pronounced anxiety, androgen deficiency, chronic fatigue syndrome, and clinically significant hyperglycemia.

Maximum Dosage (Powder): 10 grams per day. Used under medical supervision for severe forms of asthenoneurotic disorders, immunodeficiency states, and androgen deficiency in male infertility.

Preventive Dosage (Powder): 2 grams per day for 21 days, with a repeat course no earlier than after 14 days. Recommended for chronic fatigue, anxiety, metabolic syndrome, and a history of oligoasthenozoospermia. Used in persons during periods of intense stress and in elderly patients.

Pediatric Dosage (Powder): From 12 years of age with a body weight of at least 40 kilograms — 1 gram per day in the evening. In boys with signs of delayed puberty, dose correction to 2 grams is possible under medical supervision.

Contraindications (Powder): Individual intolerance, thyrotoxicosis, gastric ulcer in the exacerbation stage. Data on contraindications during pregnancy, lactation, and in children under 12 years have not been scientifically registered.

Side Effects (Powder): Nausea, diarrhea, and dizziness have been registered when exceeding the dosage above 10 grams per day. Excessive sedative reaction is possible in persons with increased sensitivity to plant alkaloids.

Adjustment for Patient Body Weight: For patients with body weight less than 60 kilograms, it is recommended to reduce the dosage by 20–30% of the standard. For patients with body weight above 90 kilograms, an increase in dosage to 7–10 grams per day is possible under tolerability monitoring.

Preparation Method (Powder): To prepare 100 grams of product, the following is required: 100 grams of dried ashwagandha root. The root is washed, dried at a temperature of 40–45 °C until a residual moisture content of less than 10% is achieved. Ground in a mortar or mill to a fine powder, sifted through a sieve with a mesh size of 250 μm. Packaged in an airtight dark glass container.

Storage Conditions and Shelf Life (Powder): Store in a tightly closed glass or ceramic container, in a dry, dark place at a temperature of 15 to 25 °C. Avoid exposure to direct light, moisture, and electromagnetic sources. Shelf life — up to 12 months. After opening, use within 45 days.

Dry Extract — Withania somnifera

Indications (Dry Extract): Obsessive-compulsive disorder, generalized anxiety disorder, depressive disorder, asthenic syndrome, cognitive disorders in neurodegenerative diseases, stress-induced hyperglycemia, androgen deficiency, oligoasthenozoospermia, immunodeficiency states, subclinical hypothyroidism, metabolic syndrome.

Standard Dosage (Dry Extract): 250–600 milligrams of dry standardized extract (with withanolide content of 5%) once a day in the morning or evening, 30 minutes before meals.

Enhanced Dosage (Dry Extract): Up to 900 milligrams per day, in a single dose or divided into two doses, used for persistent anxiety and asthenic disorders, pronounced androgen deficiency, stress-induced cognitive impairment, and immunodeficiency.

Maximum Dosage (Dry Extract): 1200 milligrams per day. Permissible for severe neurasthenia, clinically confirmed decrease in cognitive function or androgen status, in the absence of side reactions.

Preventive Dosage (Dry Extract): 300 milligrams of dry extract once a day for 30 days, repeat course — after 1 month. Recommended for chronic fatigue, increased anxiety, metabolic syndrome, during mental and physical stress, and in gerontological practice.

Pediatric Dosage (Dry Extract): Not recommended for use in children under 12 years. From 12 years — 150 milligrams once a day with a body weight of more than 35 kg. Use in boys with delayed puberty — only under medical supervision.

Contraindications (Dry Extract): Hyperthyroidism, individual intolerance, gastric ulcer. Data on contraindications during pregnancy, lactation, and under 12 years have not been scientifically registered.

Side Effects (Dry Extract): Rare cases: diarrhea, sedation, headache when exceeding the dosage. At dosages above 1000 mg/day, lowering of blood pressure and lethargy are possible.

Adjustment for Patient Body Weight: Body weight less than 50 kg — use 50–70% of the standard dose. Body weight more than 90 kg — correction to 900 mg is possible under tolerability and side effect monitoring.

Preparation Method (Dry Extract): To obtain 100 grams of dry extract: grind 1000 grams of dried root, extract with 70% ethanol (ratio 1:10) at a temperature of 45 °C for 4 hours. Filter, evaporate the solution under vacuum to a thick consistency, dry by lyophilization or spray drying to obtain a dry extract. Sift, package in an airtight container.

Storage Conditions and Shelf Life (Dry Extract): Store in an airtight container, in a dry, dark place at a temperature of 15 to 25 °C, away from moisture sources and EMI. Shelf life — up to 24 months. After opening, use within 60 days.

Alcohol-Based Tincture — Withania somnifera

Indications (Tincture): Generalized anxiety disorder, sleep disorders, asthenic syndrome, depressive disorder, chronic fatigue syndrome, androgen deficiency, oligoasthenozoospermia, immunodeficiency states, stress-induced hyperglycemia, subclinical hypothyroidism.

Standard Dosage (Tincture): 20 drops (approximately 1 ml) of tincture 1:5 in 40% ethanol — 2 times a day, 20–30 minutes before meals. Drink with 100 ml of water.

Enhanced Dosage (Tincture): 30 drops (approximately 1.5 ml) 2–3 times a day for anxiety and adjustment disorders, pronounced asthenia, immunodeficiencies, and sleep disturbances with early awakenings.

Maximum Dosage (Tincture): 2 ml 3 times a day. Used in short courses of no more than 10 days under medical supervision for severe forms of anxiety, depression, or exhaustion after illness.

Preventive Dosage (Tincture): 10 drops once a day, for 30 days. Repeat course — after 2 weeks. Recommended for increased intellectual or physical loads, during adaptation to stress, for mild cognitive impairment, and in gerontoprophylaxis.

Pediatric Dosage (Tincture): Not recommended for use in children under 12 years due to ethanol content. From 12 years with a body weight of at least 40 kg — no more than 10 drops once a day in the evening under adult supervision.

Contraindications (Tincture): Alcoholism, gastric ulcer, hyperthyroidism, epilepsy, organic CNS lesions with convulsive syndrome, pregnancy, lactation. Contraindicated in children under 12 years due to ethanol.

Side Effects (Tincture): Dizziness, drowsiness, heartburn, diarrhea when exceeding the dosage. Allergic reactions are possible in persons with hypersensitivity to Solanaceae.

Adjustment for Patient Body Weight: For patients with body weight below 50 kg — the dosage is reduced by 25%. For body weight above 90 kg — a 20% increase in dose is permissible in the absence of side effects.

Preparation Method (Tincture): 100 grams of dried ground root are poured with 500 ml of 40% ethanol. Place in a glass container, infuse for 14 days at a temperature of 20–25 °C in the dark, shaking daily. Upon completion, filter, squeeze the residue, adjust the volume to 500 ml with 40% ethanol. Store in a dark pharmacy bottle.

Storage Conditions and Shelf Life (Tincture): Store in a dark, cool place (15–25 °C), in a tightly closed glass container, away from sources of fire and EMI. Shelf life — up to 2 years. After opening, use within 90 days.

Oil Infusion — Withania somnifera

Indications (Oil Infusion): Chronic fatigue syndrome, asthenic syndrome, androgen deficiency, oligoasthenozoospermia, neurodegenerative disorders, stress-induced anxiety states, dry skin due to neuroendocrine disorders, localized myalgias, neuroinflammatory conditions.

Standard Dosage (Oil Infusion): 2–5 ml of oil infusion for external use: daily in the form of massage for 10–15 minutes in the area of the neck, lower back, temples, or lower abdomen. Course 14–21 days.

Enhanced Dosage (Oil Infusion): Up to 10 ml per day in the form of more intensive massage or applications — for pronounced muscle tension, chronic fatigue, erectile dysfunction, male hypogonadism, and nervous disorders with autonomic manifestations.

Maximum Dosage (Oil Infusion): 15 ml per day. Used for severe myofascial contracture, chronic fatigue with physical inactivity, and postoperative asthenia. Course duration no more than 10 days without a break.

Preventive Dosage (Oil Infusion): 1–2 ml 3 times a week — in the form of self-massage of the sternum, abdomen, or feet. Indicated for a tendency to overwork, anxiety, and decreased tone in adulthood. Duration of the preventive course — 21 days, with a 14-day break.

Pediatric Dosage (Oil Infusion): From 6 years — external use of 0.5 ml in the form of a light massage of the feet or occipital area for increased fatigue and nervousness. Use no more than 3 times a week. The oil must be well filtered, without sediment.

Contraindications (Oil Infusion): Individual intolerance, dermatoses with weeping, acute pustular rashes in the application area, febrile conditions. Data on contraindications during pregnancy and lactation with external use have not been registered.

Side Effects (Oil Infusion): Rarely — contact dermatitis, itching, burning sensation with hyperreactive skin. When applied to large areas of the body — drowsiness or short-term dizziness is possible.

Adjustment for Patient Body Weight: Patients with body weight less than 45 kg — apply a dosage of 1–2 ml. For weight above 90 kg — an increase to 10 ml is possible with external use.

Preparation Method (Oil Infusion): Ground dry root — 10 grams, organic cold-pressed coconut oil — 100 grams. Combine the components in a glass container and heat in a water bath at a temperature of 45–50 °C for 3 hours, stirring periodically. Cool, filter through gauze, pour into dark vials. To obtain a concentrate, infusion for 7 days with daily shaking without heating can be carried out.

Storage Conditions and Shelf Life (Oil Infusion): Store in a dark, cool place, at a temperature of 10 to 20 °C, in a tightly sealed container, protected from EMI and sunlight. Shelf life — 6 months. After opening, use within 30 days.

Ear Drops — Withania somnifera

Indications (Ear Drops): Autoimmune otitis, neuroinflammatory otitis, sensorineural hearing loss in the initial stage, inflammation of the external auditory canal of non-infectious nature, irritation of the auditory nerve due to autonomic dystonia, post-stress ear hypersensitivity.

Standard Dosage (Ear Drops): 2 drops in each auditory canal once a day, in the evening, for 5–7 days. Apply in a lying position, pre-warming the solution to body temperature.

Enhanced Dosage (Ear Drops): 3 drops 2 times a day (morning and evening), for pronounced sensorineural symptoms, irritation of the auditory nerve, and in the initial phase of chronic non-infectious otitis.

Maximum Dosage (Ear Drops): 4 drops 2 times a day, no more than 5 days in a row. Recommended for persistent ear congestion accompanied by anxiety states or sleep disorders.

Preventive Dosage (Ear Drops): 1 drop in each auditory canal 2 times a week for 3 weeks. Indicated for frequent stress, a tendency to autonomic dysfunction, chronic fatigue, and irritability with tinnitus. Courses are repeated no more than once a month.

Pediatric Dosage (Ear Drops): From 7 years of age with a body weight of at least 25 kg — 1 drop in each auditory canal once a day for 3 days. Use only in the absence of inflammatory and infectious manifestations.

Contraindications (Ear Drops): Perforation of the tympanic membrane, acute purulent otitis, presence of exudate in the auditory canal, individual intolerance to components. Data on contraindications during pregnancy and lactation with local use are absent.

Side Effects (Ear Drops): Rarely — itching, irritation of the auditory canal, transient decrease in hearing sensitivity with excessive oil administration. Isolated cases of a feeling of "ear congestion" have been registered at a dose of more than 4 drops.

Adjustment for Patient Body Weight: Patients with body weight up to 50 kg — use the standard or preventive dosage. For body weight over 90 kg — dose correction to 3 drops 2 times a day is possible.

Preparation Method (Ear Drops): Ground dry root — 5 grams, organic jojoba oil — 50 grams. Place the mixture in a glass container, heat in a water bath at a temperature of 45–50 °C for 2 hours. Cool, filter through a cotton pad and pour into a sterile vial with a dropper. Check for the absence of sediment.

Storage Conditions and Shelf Life (Ear Drops): Store in a tightly closed glass bottle, at a temperature of 10 to 25 °C, in a light-protected place. Shelf life — up to 3 months. After opening, use within 15 days. Do not allow water to enter the bottle.

Ointment — Withania somnifera

Indications (Ointment): Arthralgia, myalgia, fibromyalgia, osteoarthritis, tendon inflammation, neuropathic pain, localized neuritis, senile sarcopenia, stress-induced muscle tension, pseudoradiculopathy, peripheral neuroinflammatory reaction.

Standard Dosage (Ointment): Apply 1.5–2 grams of ointment (a strip of 2–3 cm) to the affected area 2 times a day with light circular movements until absorbed. Course 10–14 days.

Enhanced Dosage (Ointment): 3–4 grams of ointment 2–3 times a day for chronic inflammatory and pain syndromes in muscles, joints, or nerves. Use until persistent reduction of symptoms.

Maximum Dosage (Ointment): Up to 5 grams of ointment 3 times a day for no more than 7 days in a row. Recommended for pronounced neuralgic pain, limited joint mobility, and contractures.

Preventive Dosage (Ointment): 1 gram of ointment 3 times a week on areas of increased tension (neck, lower back, occiput). Use for a sedentary lifestyle, increased psycho-emotional loads, and in elderly patients with signs of sarcopenia. Course — 21 days with a 14-day break.

Pediatric Dosage (Ointment): From 10 years — no more than 0.5 grams of ointment per zone once a day, no more than 5 days in a row. Used for localized pain or muscle tension. Do not apply to mucous membranes and open wounds.

Contraindications (Ointment): Open skin lesions, eczematous processes, purulent skin lesions, individual intolerance. Data on contraindications during pregnancy and lactation with external use have not been registered.

Side Effects (Ointment): Local skin irritation, hyperemia, peeling, allergic contact dermatitis with prolonged use or exceeding the dosage.

Adjustment for Patient Body Weight: Patients with body weight less than 50 kg — do not exceed 2 grams per day. For weight over 90 kg — correction to 5 grams 2 times a day is possible.

Preparation Method (Ointment): Dry ashwagandha root extract (withanolides 5%) — 5 grams, organic coconut oil — 15 grams, beeswax — 10 grams, lanolin — 10 grams, purified water — 60 grams. Melt the wax and coconut oil in a water bath, add the extract and lanolin, mix thoroughly. Add water, constantly stirring until emulsification. Cool at room temperature, package in a sterile dark glass jar.

Storage Conditions and Shelf Life (Ointment): Store in an airtight glass jar, at a temperature of 5 to 15 °C in the dark. Avoid moisture ingress. Shelf life — up to 3 months. After opening, use within 30 days.

Cream — Withania somnifera

Indications (Cream): Age-related changes of the facial skin, stress-induced dry skin, dermatological manifestations in the climacteric period, skin hypersensitivity in autonomic dysfunction, neurodermatitis in remission, skin irritation in chronic fatigue, sagging and decreased skin tone.

Standard Dosage (Cream): Apply 1–1.5 grams of cream (a strip of about 2 cm) to pre-cleansed facial or body skin 1–2 times a day, evenly distributing in a thin layer. Course of use — 21 days.

Enhanced Dosage (Cream): Up to 2 grams of cream 2–3 times a day, for pronounced dryness, sensitivity, age-related skin laxity, after stress loads, or after prolonged exposure to sun/cold.

Maximum Dosage (Cream): 3 grams 3 times a day, no more than 7 days in a row. Use for acute stress reactions of the skin, after dermatological procedures, and for menopausal skin reactions.

Preventive Dosage (Cream): 1 gram once a day in the evening, in a 14-day course. Used for age-related changes, decreased skin tone, mild manifestations of skin anxiety (in the form of itching, tingling), during climate changes, and in patients with chronic fatigue syndrome.

Pediatric Dosage (Cream): From 6 years — no more than 0.3 grams once a day for dry skin of the elbows, hands, and cheeks. Use only on intact skin. Without flavorings and essential oils.

Contraindications (Cream): Acute inflammatory skin diseases, weeping eczema, individual intolerance. Scientific data on contraindications during pregnancy and lactation in external form are absent.

Side Effects (Cream): Mild redness, itching, and peeling are possible with hypersensitivity to components. No systemic side effects have been noted with external use.

Adjustment for Patient Body Weight: Not required for external use. With increased skin sensitivity, it is recommended to start with half of the standard dosage.

Preparation Method (Cream): Dry ashwagandha root extract — 3 grams, lavender hydrolate — 40 grams, organic coconut oil — 20 grams, emulsifier (glycerol stearate) — 5 grams, beeswax — 5 grams, vitamin E — 1 gram, purified water — 26 grams. Heat the oil and aqueous phases separately to 65 °C, then combine with constant stirring. After thickening, introduce the extract and vitamin E, stir until room temperature. Package in a dark dispenser bottle.

Storage Conditions and Shelf Life (Cream): Store in the refrigerator at a temperature of 5 to 8 °C, away from light and moisture, in an airtight package. Shelf life — 2 months. After opening, use within 21 days. Do not allow water to enter the bottle.

Serum — Withania somnifera

Indications (Serum): Age-related skin dehydration, skin hypersensitivity due to chronic stress, dermatological manifestations in the climacteric period, atopic reactions in remission, skin recovery after aggressive cosmetic procedures, post-acne, dullness and decreased microcirculation of the facial skin.

Standard Dosage (Serum): 0.5–1 ml of serum is applied to cleansed facial and neck skin once a day in the evening, with light patting movements until completely absorbed. Course of use — 21–28 days.

Enhanced Dosage (Serum): 1 ml 2 times a day — morning and evening — for pronounced stress-induced dehydration, skin barrier disruption, menopausal changes, and after aesthetic procedures (laser, peeling, microdermabrasion).

Maximum Dosage (Serum): 1.5 ml 2 times a day for no more than 5 days in a row. Use in intensive courses for pronounced age-related changes, dull and "tired" skin, and significant loss of elasticity and turgor.

Preventive Dosage (Serum): 0.3–0.5 ml once a day at night, for 14 days. Indicated in the autumn-winter period, during chronic stress, sleep disturbances, in patients over 40 years of age, and in residents of megacities with increased air pollution.

Pediatric Dosage (Serum): Not used in pediatrics. No safety data for external use in the form of serum in children are available.

Contraindications (Serum): Active inflammatory skin diseases, individual intolerance to components. No registered contraindications during pregnancy and lactation with external use have been identified, but use is not recommended without specialist consultation.

Side Effects (Serum): Rarely — tingling, redness, mild itching in the first 5 minutes after application. Allergic reactions are possible with individual intolerance. Scientifically confirmed systemic side effects have not been registered.

Adjustment for Patient Body Weight: Dose adjustment by body weight is not required. Adjustment should be made according to the state of the skin barrier and skin type.

Preparation Method (Serum): Dry ashwagandha extract (withanolides 5%) — 1 gram, damask rose hydrolate — 50 grams, aloe vera extract (aqueous) — 20 grams, low molecular weight hyaluronic acid — 0.5 grams, vegetable glycerin — 3 grams, plant-based preservative — 0.5 grams, purified water — up to 100 grams. Combine all components at a temperature of 25–30 °C, stir until homogeneous, filter, pour into dropper bottles.

Storage Conditions and Shelf Life (Serum): Store at a temperature of 4 to 8 °C, in a tightly closed dark glass container, away from sunlight and heat sources. Shelf life — 30 days. After opening, use within 14 days, avoiding the ingress of water and air into the container.

Toxicity and Biosafety of Withania somnifera

Studies on the toxicological profile of Withania somnifera demonstrate a high degree of biosafety in both acute and chronic use of root extract. In a series of preclinical trials on various laboratory animals (mice, rats, guinea pigs), it was established that the LD₅₀ of the aqueous-alcoholic root extract exceeds 2000 mg/kg with oral administration in rats, which corresponds to low toxicity according to the WHO classification.

Chronic administration of doses up to 1000 mg/kg for 90 days did not cause significant changes in hematological and biochemical parameters, or in the morphology of the liver, kidneys, heart, and lungs. No mutagenic or carcinogenic potential was detected.

It is important to note that a higher concentration of withaferin A, characteristic of Withania somnifera leaves, may have pronounced cytotoxic activity and requires separate assessment. However, when using standardized root extracts, toxic effects are absent even at dosages exceeding therapeutic ones by 20–25 times.

Data on use in pregnant women and in pediatrics are limited. It is not recommended to use high dosages without specialist supervision in these patient groups.

Reference: Ashwagandha (Withania somnifera) Safety Assessment – National Library of Medicine

Pharmacodynamics — Withania somnifera

The pharmacodynamic properties of Withania somnifera are due to a complex of biologically active compounds, the main of which are withanolides (withaferin A, withanolide D), alkaloids (including vitanine, somniferine), sitoindosides, and phytosteroids. These compounds have diverse biochemical activity, mediated by effects on nervous, immune, endocrine, and metabolic regulation at the systemic and cellular levels.

At the level of the central nervous system, Withania somnifera exhibits a modulating effect through its influence on gamma-aminobutyric acid (GABA), serotonergic, and glutamatergic transmission. In vivo studies demonstrate that root extracts reduce the activity of cortisol-dependent stress responses, regulating the hypothalamic-pituitary-adrenal axis. The mechanism of action includes activation of GABA-A receptors and suppression of corticotropin-releasing hormone activity, which leads to a decrease in CNS excitability and enhancement of inhibitory neurotransmission. The ability of withanolides to stabilize synaptic transmission, improve neuronal plasticity, and reduce neuroinflammation has been established.

On the immune system, Withania somnifera acts through the normalization of the functional activity of macrophages, neutrophils, and natural killer cells. An increase in the expression of interleukins IL-2 and IL-12, enhanced IgG production, and a modulating effect on the Th1/Th2 balance have been noted. Studies also demonstrate an effect on NF-κB expression and suppression of pro-inflammatory cytokines (including TNF-α and IL-6), indicating an immunomodulatory and anti-inflammatory profile of action.

At the level of the endocrine system, the effect of Withania somnifera on androgen and thyroid receptors has been established. Withanolides activate the transcription of genes responsible for the synthesis of steroid hormones and the maintenance of homeostasis of the pituitary-gonadal axis. Normalization of triiodothyronine and thyroxine levels, as well as a decrease in adrenocorticotropic hormone levels with long-term use, has been shown. This indicates the ability of the plant to affect hormonal regulation under conditions of functional destabilization.

Metabolically active components of Withania somnifera exhibit antioxidant properties through the induction of superoxide dismutase, catalase, and glutathione peroxidase. They reduce malondialdehyde levels, inhibit lipid peroxidation, and contribute to the protection of mitochondrial activity. This effect is especially pronounced in the tissues of the liver, kidneys, and brain, confirming systemic antioxidant activity.

From the gastrointestinal tract, the ability to normalize gastric secretion, improve mucosal trophism, and stimulate intestinal motor activity has been identified. A mild spasmolytic effect and normalization of hepatobiliary system functions have also been established. Studies demonstrate anti-apoptotic effects on hepatocytes and restoration of the antioxidant status of the liver under toxic loads.

At the level of the skin, Withania somnifera exhibits angioprotective and reparative effects, accelerating tissue regeneration and reducing the reactivity of skin receptors. Local application stimulates collagen synthesis and improves microcirculation in the dermis, which is associated with the content of phytosteroids and antioxidant metabolites.

Thus, Withania somnifera demonstrates multisystem action involving neurotransmitter, cytokine, hormonal, and enzymatic mechanisms. Effects on targets include GABA receptors, cytokine cascades, nuclear hormone receptors, antioxidant enzymes, inflammatory transcription factors (NF-κB), and cellular receptors for protection against stress factors.

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

Pharmacokinetics — Withania somnifera

The pharmacokinetics of Withania somnifera as a medicinal taxon is largely determined by its pharmacological form (powder, dry extract, alcohol tincture, oil infusion, topical forms), as well as the structural features of the main groups of compounds, such as withanolides, alkaloids, steroid lactones, flavonoids, and fat-soluble antioxidants.

With oral administration of powder and dry extract, active absorption of most low-molecular-weight components occurs in the upper parts of the small intestine. Substances penetrate the intestinal barrier mainly by passive diffusion, and to a lesser extent through active transport. The presence of fats in food can enhance the absorption of lipophilic components, especially withanolides. Alkaloids and steroid lactones undergo primary metabolism in the intestinal mucosa and enterocytes, which affects their systemic availability.

Metabolism of active substances is carried out mainly in the liver with the participation of cytochrome P450 enzymes. Hepatic transformation includes hydroxylation, demethylation, and conjugation with glucuronic acid, which is characteristic of most phytosteroids and alkaloids. After biotransformation, the compounds become more polar, which facilitates their excretion. Some biologically active metabolites may exhibit independent pharmacological activity, maintaining action at the level of target tissues.

Distribution in the body depends on the lipophilicity of the substances. The most pronounced accumulation is assumed in structures with a high lipid content — including the central nervous system, endocrine glands, and liver. The ability of individual withanolides to cross the blood-brain barrier is assumed, which explains their action on central neurotransmitter systems.

With transdermal use (oil forms, creams, ointments), absorption is limited by the stratum corneum of the skin; however, fractions of fat-soluble components penetrate into the deep layers of the dermis and subcutaneous adipose tissue. In these conditions, the substances exert mainly local and regional effects, and systemic absorption is minimal. Enhanced penetration is possible with prolonged application, massage, increased skin temperature, or disruption of its barrier function.

Through mucous membranes (in the form of ear drops or hypothetical nasal forms), absorption of some active metabolites with rapid entry into the systemic bloodstream is possible, bypassing the first-pass effect through the liver. This allows achieving a faster onset of action with local or neuroendocrine effects.

Excretion of metabolites occurs primarily through the kidneys (in urine) and bile. The liver plays a key role in detoxification and preparation of molecules for excretion. To a lesser extent, excretion of volatile fractions and low-polarity components through the skin and lungs is possible. No traces of systemic cumulative accumulation in a healthy body have been found; however, with impaired liver or kidney function, metabolite retention and changes in the action profile are possible.

It has also been established that with long-term use, the formation of functional bioavailability is possible against the background of adaptation of the gastrointestinal microflora, which participates in the breakdown of complex phytosteroids and increases the proportion of absorbed aglycones. This indicates a possible role of the microbiota in the regulation of the pharmacokinetics of Withania somnifera with oral use.

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

Mechanisms of Action and Scientific Rationale — Withania somnifera

The pharmacological activity of Withania somnifera is due to a combination of biologically active metabolites, including withanolides, alkaloids, flavonoids, steroid lactones, and phytosteroids. One of the key directions of action is the modulation of the hypothalamic-pituitary-adrenal (HPA) axis, accompanied by a decrease in corticotropin and cortisol levels, which is realized through suppression of CRH activity and subsequent inhibition of the glucocorticoid cascade. This mechanism is partly due to the ability of some withanolides to bind to glucocorticoid receptors and indirectly reduce their activation. In parallel, the expression of GABA-A receptors is activated, which contributes to the enhancement of inhibitory neurotransmission and regulation of central excitation.

At the cellular level, the effect of Withania somnifera extracts on signaling cascades regulating inflammation and cellular stress has been established. The main targets are NF-κB and MAPK pathways, through which the plant inhibits the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. In parallel, suppression of cyclooxygenase-2 (COX-2) and lipoxygenase (5-LOX) expression has been noted, which reduces the biosynthesis of pro-inflammatory prostaglandins and leukotrienes. This creates the basis for anti-inflammatory and immunomodulatory effects on macrophages, neutrophils, and monocytes.

Phytosteroids and withanolides participate in the regulation of androgen and thyroid signaling cascades. It has been established that plant components can increase the expression of androgen receptors and activate transcriptional elements responsible for the synthesis of steroid hormones. Enhanced production of triiodothyronine (T3) and thyroxine (T4) has also been recorded, which is associated with modulation of iodothyronine deiodinase activity in the liver. These effects allow endocrine regulation to be considered as one of the leading mechanisms of action of the taxon.

Neuroprotective properties of Withania somnifera are realized through a reduction in lipid peroxidation, activation of antioxidant defense enzymes (catalase, superoxide dismutase, glutathione peroxidase), and suppression of reactive oxygen species formation. At the same time, stabilization of neuronal membrane structures and improvement of signal transmission in synapses are observed. Withanolides also demonstrate the ability to inhibit acetylcholinesterase (AChE), contributing to enhanced cholinergic neurotransmission.

Effects on the immune system include normalization of Th1/Th2 cell balance, increased activity of natural killer (NK) cells, enhanced phagocytosis, and MHC-II expression on the surface of antigen-presenting cells. These processes are accompanied by an increase in IL-12 and IFN-γ synthesis and a decrease in pro-inflammatory factors, reflecting adaptive and innate immunomodulatory effects.

Additionally, it has been established that Withania somnifera affects metabolic processes, including the regulation of adipocytokines, glucose transport, and lipid metabolism, mediated through the activation of PPAR-γ receptors and a decrease in SREBP-1c expression. This is complemented by a decrease in α-amylase and α-glucosidase activity in in vitro modeling, confirming involvement in the regulation of carbohydrate homeostasis.

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

Synergy — Withania somnifera

Withania somnifera exhibits pronounced pharmacological synergy with a number of plant and natural substances, as confirmed by preclinical and clinical studies. The main directions of interaction include potentiation of neuroprotective, adaptogenic, antioxidant, and immunomodulatory effects. Combination with other substances allows enhancing bioavailability, expanding the spectrum of targets, and increasing the body's resistance to stress factors.

One well-documented example is the synergy of Withania somnifera with Panax ginseng, in which potentiation of the effect on the hypothalamic-pituitary-adrenal axis is observed. This interaction is realized through the activation of glucocorticoid receptors and enhancement of adaptive reactions during physical and mental stress. In vivo studies confirm enhanced anti-stress activity and regulation of neurotransmitter systems with the simultaneous use of these taxa.

In combination with Curcuma longa (turmeric), Withania somnifera demonstrates a potentiating anti-inflammatory and antioxidant effect. Interaction mechanisms include combined suppression of NF-κB, COX-2, and TNF-α expression, as well as enhanced activity of superoxide dismutase and glutathione peroxidase. At the same time, withanolides enhance the tissue-specific action of curcuminoids, especially in the structures of the liver and central nervous system.

Synergy with Bacopa monnieri is realized mainly in the nervous system. Both plants contribute to an increase in BDNF expression and modulate cholinergic transmission. The combined effect is aimed at improving cognitive function, reducing neuroinflammation, and stabilizing synaptic plasticity. The nature of the interaction is predominantly additive with elements of potentiation.

When combined with extracts of Glycyrrhiza glabra, a protective effect on the gastric mucosa and enhancement of systemic antioxidant activity are observed. This is due to the combined reduction of malondialdehyde levels and suppression of lipid peroxidation in tissues. The natural saponins of licorice also enhance the absorption of fat-soluble metabolites of ashwagandha with oral administration.

With Rhodiola rosea, complementation of adaptogenic action has been recorded due to the parallel effect on the catecholaminergic system and regulation of dopamine and norepinephrine levels. Withanolides and rosavins act in different neurotransmitter cascades, providing a modulating effect on nervous excitability and resistance to stress.

Additionally, potentiation of the immunomodulatory effect is noted when combining Withania somnifera with Tinospora cordifolia. In vivo studies have shown enhanced lymphocyte proliferation, macrophage activation, and normalization of the Th1/Th2 balance with combined use. The interaction mechanism involves the activation of JAK/STAT and suppression of pro-inflammatory cytokines through independent signaling pathways.

Thus, Withania somnifera is a universal phytobiomodulator with a high potential for synergy in multicomponent compositions with both adaptogens and anti-inflammatory and antioxidant plants. Confirmed interaction mechanisms include combined effects on transcription factors (NF-κB, CREB), mediator systems (GABA, dopamine, cytokines), enzyme targets (COX, AChE), and hormonal regulators (androgen and glucocorticoid receptors).

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

Geography of Use and Traditional Medicine — Withania somnifera

Withania somnifera, better known by its traditional Indian name ashwagandha, has a long history of use in the ethnomedical systems of South Asia, the Middle East, North and East Africa, and partly in the southern regions of Europe. The main center of historical use is the Indian subcontinent, where ashwagandha is one of the basic plants of classical Ayurvedic medicine. According to the texts of the "Charaka Samhita" and "Sushruta Samhita," the plant is described as a rasayana — a means for prolonging life and restoring vitality. Mentions of Withania somnifera in Sanskrit literature presumably date back to no later than the 1st millennium BC.

In the Ayurvedic tradition, various parts of the plant were used, but the root was considered the most important. It was used in the form of powder, decoction, paste for wraps, and also mixed with oil or milk. It was believed that ashwagandha strengthens the body, promotes recovery after overexertion, and harmonizes the psycho-emotional state. In traditional village practices of the states of Rajasthan, Gujarat, Karnataka, and Maharashtra, root infusion was used for rubbing infants, as well as in rites of passage into adulthood. The root could also be hung over the entrance to a dwelling as an amulet against the evil eye and disease.

In the traditions of Yemeni and Ethiopian folk medicine, Withania somnifera was used as a tonic and added to hot infusions for rubs and baths. Among the Bedouin tribes of North Africa, there was a practice of rubbing the body with an ash solution from the ashwagandha root, and in Tuareg culture, it was part of ritual incense used by shamans to induce visions and purify the mind.

In Persian-Arab traditional medicine, the plant is found under the name "khasbakhanda," where it was considered a remedy that strengthens the brain and spirit. It was used in the form of a thick decoction with honey as a tonic and soothing remedy. In Egypt, dried root was added to compositions with other aromatic plants used in fumigations and steam baths.

In Nepal and Tibet, Withania somnifera is found in the phytocollections of Tibetan medicine, where the plant was identified with the elements of earth and air, and its action was associated with balancing the lung energy (wind). Tibetan healers used dried parts of the root in oil wraps and dry powder rubs, accompanied by breathing practices and meditation.

In African countries such as Kenya, Tanzania, and Sudan, ashwagandha is also included in traditional herbal tinctures and powders used by community elders in rituals of restoring strength after illness or a difficult life event. In some ethnic groups, the root was used as a component of ritual incense before important events, including initiations and funeral ceremonies.

In Europe, the plant has been known since antiquity as "Indian cherry" and is found in some medieval herbal books, mainly of Arabic origin, where it was recommended as a tonic remedy. In recent centuries, its use has been episodic, mainly in monastic and rural medicine of Spain and Southern Italy.

Thus, Withania somnifera has one of the richest and most documented ethnomedical biographies among the adaptogenic plants of the Old World. It is integrated into rituals, therapeutic practices, and cultural rites in more than two dozen regional and ethnic medical schools of the world.