​Silybum marianum (Milk Thistle)

Silybum marianum (Milk Thistle)

Product Name: Расторопша пятнистая, Silybum marianum, Mariendistel, Cardo mariano, Chardon-Marie, حرشف اللبن, เกล็ดน้ำนม, Sut alang, Сүт тикени, Südən qırxbuğumu, Ширешафақ, Margainis, Piena dadzis, Розторопша плямиста, חוחלב

Synonyms: чертополох молочный, молочный чертополох, milk thistle, blessed milk thistle, holy thistle, lady’s thistle, Mariendistel, Milchdistel, Kardendistel, cardo lechoso, cardo de María, cardo mariano bendito, chardon-Marie, chardon béni, الحرشف المبارك, شوك الحليب, เกล็ดน้ำนม, น้ำนมหนาม, หญ้าน้ำนม

Parts used: roots, stems, leaves, flowers, fruit, seeds

Main indications for the use of Silybum marianum: toxic liver damage, drug-induced hepatitis, alcoholic liver disease, liver cirrhosis, non-alcoholic fatty liver disease, viral hepatitis, cholangitis, cholecystitis, biliary dyskinesia, dyspepsia, hyperlipidemia, atherosclerosis.

Indications for the use of Silybum marianum in mixtures and complexes: chronic pancreatitis, gastroduodenitis, chronic gastritis, irritable bowel syndrome, obesity, type 2 diabetes mellitus, metabolic syndrome, psoriasis, eczema, acne, rheumatoid arthritis, systemic lupus erythematosus.

Main pharmacological properties of Silybum marianum: Hepatoprotective, antioxidant, anti-inflammatory, membrane-stabilizing, choleretic, hypolipidemic, antitoxic, immunomodulatory, antifibrotic, anticarcinogenic, antidiabetic, cardioprotective, neuroprotective, dermatoprotective.

Dosage of pharmaceutical forms — Silybum marianum

Powder — Silybum marianum

Indications (Powder): toxic liver damage, alcoholic liver disease, drug-induced hepatitis, liver cirrhosis, non-alcoholic fatty liver disease, viral hepatitis, hyperlipidemia, atherosclerosis, dyspepsia.

Standard Dosage (Powder): orally at 1.5 grams of seed powder 2 times a day, with 150 milliliters of warm water, course of 30 days.

Enhanced Dosage (Powder): orally at 2 grams of seed powder 3 times a day for drug-induced hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease.

Maximum Dosage (Powder): orally at 3 grams of seed powder 3 times a day for liver cirrhosis, severe toxic liver damage, chronic viral hepatitis.

Preventive Dosage (Powder): orally at 1 gram of seed powder once a day for patients with chronic gastritis, biliary dyskinesia, hyperlipidemia, as well as for patients over 50 years of age for preventive purposes; prevention course — 30 days with a 60-day break.

Pediatric Dosage (Powder): for children over 12 years old and weighing more than 40 kilograms — orally at 0.5 grams of seed powder once a day; for younger children, dosage data have not been scientifically registered.

Contraindications (Powder): individual intolerance, acute cholecystitis, acute pancreatitis; data on contraindications during pregnancy, lactation, and in children under 12 years of age have not been scientifically registered.

Side Effects (Powder): upon overdose, diarrhea, flatulence, nausea may develop.

Adjustment for Patient Body Weight: for body weight below 60 kilograms — dosage reduction by 25 percent; for body weight above 90 kilograms — dosage increase by 25 percent.

Preparation method (Powder): To prepare 100 grams of powder: take 100 grams of dry plant seeds. Clean the seeds from mechanical impurities, dry at a temperature not exceeding 40 degrees Celsius, grind in a micromill or mortar to a fine powder state, sieve through a sieve with a mesh size of 0.5 millimeters. Store in an airtight container.

Storage Conditions and Shelf Life (Powder): store in a tightly closed glass or ceramic container, at a temperature of 15 to 25 degrees Celsius, in a dry room, protected from direct light and sources of electromagnetic radiation. Shelf life — up to 12 months. After opening, use within 60 days.

Dry Extract — Silybum marianum

Indications (Dry Extract): toxic liver damage, drug-induced hepatitis, liver cirrhosis, viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, cholangitis, cholecystitis.

Standard Dosage (Dry Extract): orally at 200 milligrams of dry extract (in terms of silymarin) 2 times a day, course of 30 days.

Enhanced Dosage (Dry Extract): orally at 300 milligrams of dry extract 3 times a day for alcoholic liver disease, chronic viral hepatitis, non-alcoholic fatty liver disease.

Maximum Dosage (Dry Extract): orally at 400 milligrams of dry extract 3 times a day for liver cirrhosis, severe toxic liver damage.

Preventive Dosage (Dry Extract): orally at 100 milligrams of dry extract once a day for patients with hyperlipidemia, dyspepsia, chronic gastritis; prevention course — 30 days with a 90-day break.

Pediatric Dosage (Dry Extract): for children over 12 years old and weighing more than 40 kilograms — orally at 100 milligrams of dry extract once a day; use in children under 12 years of age is not recommended.

Contraindications (Dry Extract): individual intolerance, acute cholecystitis, acute pancreatitis; data on contraindications during pregnancy and lactation are limited, there are no scientifically confirmed data.

Side Effects (Dry Extract): upon overdose, diarrhea, flatulence, headache may develop.

Adjustment for Patient Body Weight: for body weight below 60 kilograms — dosage reduction by 20 percent; for body weight above 90 kilograms — dosage increase by 20 percent.

Preparation method (Dry Extract): To prepare 100 grams of dry extract: take 500 grams of crushed plant seeds, pour 1500 milliliters of 70 percent ethanol. Infuse for 7 days at room temperature, stirring periodically. Perform filtration, then evaporate the solution in a water bath at a temperature not exceeding 50 degrees Celsius until complete removal of ethanol. Control of removal — complete disappearance of the alcohol odor. Dry the resulting thick extract in a vacuum drying oven at a temperature not exceeding 45 degrees Celsius to a powder state. Permissible residual ethanol content in the dry extract — no more than 50 ppm.

Storage Conditions and Shelf Life (Dry Extract): store in a tightly closed container made of opaque material, at a temperature of 15 to 25 degrees Celsius, in a dry room, protected from light and moisture. Shelf life — up to 24 months. After opening, use within 90 days.

Tincture — Silybum marianum

Indications (Tincture): toxic liver damage, drug-induced hepatitis, liver cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis, cholecystitis, cholangitis.

Standard Dosage (Tincture): orally at 20 drops of alcohol tincture, diluted in 50 milliliters of water, 2 times a day before meals, course of 30 days.

Enhanced Dosage (Tincture): orally at 30 drops of alcohol tincture 3 times a day for chronic viral hepatitis, alcoholic liver disease.

Maximum Dosage (Tincture): orally at 40 drops of alcohol tincture 3 times a day for liver cirrhosis, severe toxic liver damage.

Preventive Dosage (Tincture): orally at 10 drops of alcohol tincture once a day for patients with chronic gastritis, hyperlipidemia, dyspepsia; prevention course — 30 days with a 90-day break.

Pediatric Dosage (Tincture): not used in children under 12 years of age; in adolescents over 12 years old, taking 5 drops of tincture diluted in water once a day is possible; data for younger children are absent.

Contraindications (Tincture): individual intolerance, acute pancreatitis, acute cholecystitis, alcoholism, epilepsy, traumatic brain injuries, pregnancy, lactation; data on contraindications in pediatrics are limited.

Side Effects (Tincture): upon overdose, nausea, diarrhea, headache, increased allergic reactions may develop.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, the dosage is reduced by 25 percent; for body weight above 90 kilograms, the dosage is increased by 25 percent.

Preparation method (Tincture): To prepare 100 milliliters of tincture: take 20 grams of crushed plant seeds, pour 100 milliliters of 40 percent ethanol. Infuse in dark glass at room temperature for 10 days, shaking daily. Perform filtration through filter paper. The solvent (ethanol) is a finished component and is not removed. Use only diluted.

Storage Conditions and Shelf Life (Tincture):store in a tightly closed dark glass bottle, at a temperature of 8 to 20 degrees Celsius, in a place protected from light. Shelf life — up to 24 months. After opening, use within 6 months.

Oil Infusion — Silybum marianum

Indications (Oil Infusion): non-alcoholic fatty liver disease, hyperlipidemia, atherosclerosis, chronic gastritis, dyspepsia, psoriasis, eczema, atopic dermatitis.

Standard Dosage (Oil Infusion): orally at 1 teaspoon (5 milliliters) of oil 2 times a day 30 minutes before meals, course of 30 days.

Enhanced Dosage (Oil Infusion): orally at 1 dessert spoon (10 milliliters) of oil 2 times a day for non-alcoholic fatty liver disease, hyperlipidemia, atherosclerosis.

Maximum Dosage (Oil Infusion): orally at 1 tablespoon (15 milliliters) of oil 2 times a day for pronounced hyperlipidemia, toxic liver damage.

Preventive Dosage (Oil Infusion): orally at 1 teaspoon (5 milliliters) of oil once a day for patients with chronic gastritis, biliary dyskinesia, hyperlipidemia; prevention course — 20 days with a 60-day break.

Pediatric Dosage (Oil Infusion): for children over 6 years old — 1 milliliter of oil once a day; for children under 6 years old, dosage data have not been scientifically registered.

Contraindications (Oil Infusion): individual intolerance, acute cholecystitis, acute pancreatitis; data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Oil Infusion): upon overdose, diarrhea, abdominal pain, allergic reactions may develop.

Adjustment for Patient Body Weight: for body weight below 60 kilograms, reduce the dosage by 20 percent; for body weight above 90 kilograms, increase the dosage by 20 percent.

Preparation method (Oil Infusion): To prepare 100 grams of infusion: take 20 grams of plant seeds, grind into powder, pour 100 grams of coconut oil. Infuse in a dark place at a temperature of 25 degrees Celsius for 14 days, shaking daily. After infusion, filter through cheesecloth. Store in an airtight container.

Storage Conditions and Shelf Life (Oil Infusion): store in a tightly closed dark glass bottle, at a temperature of 8 to 20 degrees Celsius, in a place protected from light. Shelf life — up to 12 months. After opening, use within 60 days.

Cream — Silybum marianum

Indications (Cream): psoriasis, eczema, atopic dermatitis, seborrheic dermatitis, acne, photodermatosis, burns of I–II degree, trophic ulcers.

Standard Dosage (Cream): external application 2 times a day to affected skin areas in a thin layer, course of 20–30 days.

Enhanced Dosage (Cream): external application 3 times a day for pronounced manifestations of psoriasis, eczema, atopic dermatitis.

Maximum Dosage (Cream): external application up to 4 times a day for exacerbation of acne, seborrheic dermatitis, photodermatosis.

Preventive Dosage (Cream): external application once a day at night for patients with dry skin, predisposition to allergic dermatoses, with chronic atopic dermatitis in remission; prevention course — 20 days with a 60-day break.

Pediatric Dosage (Cream): for children over 6 years old — external application once a day to affected skin areas; in children under 6 years old, data have not been scientifically registered.

Contraindications (Cream): individual intolerance, open bleeding wounds, purulent skin processes; data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Cream): upon overdose or too frequent use, contact dermatitis, local hyperemia may develop.

Adjustment for Patient Body Weight: dosage adjustment is not required, as the product is for external use.

Preparation method (Cream): To prepare 100 grams of cream: take 20 grams of dry seed extract, 10 grams of milk thistle oil, 50 grams of coconut oil, 15 grams of beeswax, 5 grams of glycerin. Melt coconut oil and wax in a water bath at a temperature of 50 degrees Celsius, add milk thistle oil and dry extract, mix thoroughly until homogeneous, add glycerin, stir for 10 minutes until creamy consistency. Pour into sterile containers.

Storage Conditions and Shelf Life (Cream): store in a dark place at a temperature of 5 to 8 degrees Celsius, in a tightly closed container; shelf life — up to 6 months. After opening, use within 30 days.

Cosmetic Cream — Silybum marianum

Indications (Cosmetic Cream): skin photoaging, dry skin, wrinkles, hyperpigmentation, rosacea, couperose, post-acne.

Standard Dosage (Cosmetic Cream): external application once a day to cleansed skin of the face and neck, course of 30 days.

Enhanced Dosage (Cosmetic Cream): external application 2 times a day for pronounced signs of skin photoaging and hyperpigmentation.

Maximum Dosage (Cosmetic Cream): external application up to 3 times a day for pronounced dry skin, wrinkles, and couperose.

Preventive Dosage (Cosmetic Cream): external application once a day at night for patients with increased skin photosensitivity, for women over 40 years of age for preventive purposes; prevention course — 20 days with a 60-day break.

Pediatric Dosage (Cosmetic Cream): use in children is not recommended, data have not been scientifically registered.

Contraindications (Cosmetic Cream): individual intolerance, acute inflammatory skin processes; data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Cosmetic Cream): upon overdose, contact dermatitis, local hyperemia, itching may develop.

Adjustment for Patient Body Weight: dosage adjustment is not required, as the product is for external use.

Preparation method (Cosmetic Cream): To prepare 100 grams of cream: take 15 grams of milk thistle oil, 10 grams of coconut oil, 5 grams of shea butter, 10 grams of dry seed extract, 55 grams of distilled water, 5 grams of beeswax. Melt wax, coconut oil, and shea butter in a water bath at a temperature of 50 degrees Celsius, add milk thistle oil and dry extract, mix. Introduce distilled water in a thin stream, whisking the mass with a mixer until an emulsion is obtained. Pour into sterile containers.

Storage Conditions and Shelf Life (Cosmetic Cream): store at a temperature of 5 to 8 degrees Celsius, in a place protected from light; shelf life — 6 months. After opening, use within 30 days.

Oil-Butter — Silybum marianum

Indications (Oil-Butter): dry skin, skin photoaging, wrinkles, hyperpigmentation, atopic dermatitis, eczema, psoriasis.

Standard Dosage (Oil-Butter): external application once a day to affected or dry skin areas in a thin layer, course of 20–30 days.

Enhanced Dosage (Oil-Butter): external application 2 times a day for pronounced dry skin, photoaging, hyperpigmentation.

Maximum Dosage (Oil-Butter): external application up to 3 times a day for exacerbation of atopic dermatitis, psoriasis, eczema.

Preventive Dosage (Oil-Butter): external application once a day at night for patients over 40 years of age with signs of photoaging; prevention course — 20 days with a 60-day break.

Pediatric Dosage (Oil-Butter): for children over 6 years old — application in a thin layer once a day to dry skin areas; in younger children, data have not been scientifically registered.

Contraindications (Oil-Butter): individual intolerance, acute purulent skin processes; data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Oil-Butter): upon overdose or too frequent use, skin irritation, contact dermatitis may develop.

Adjustment for Patient Body Weight: dosage adjustment is not required, as the product is for external use.

Preparation method (Oil-Butter): To prepare 100 grams of product: take 20 grams of milk thistle oil, 40 grams of coconut oil, 30 grams of shea butter, 10 grams of dry seed extract. Melt the oils in a water bath at a temperature of 45 degrees Celsius, add the dry extract, mix thoroughly, pour into a container and cool until solidified.

Storage Conditions and Shelf Life (Oil-Butter): store in a tightly closed container at a temperature of 5 to 10 degrees Celsius, in a place protected from light. Shelf life — 12 months. After opening, use within 60 days.

Carrier Gel — Silybum marianum

Indications (Carrier Gel): acne, rosacea, photodermatosis, seborrheic dermatitis, hyperpigmentation, post-acne.

Standard Dosage (Carrier Gel): external application 2 times a day in a thin layer to affected skin areas, course of 20–30 days.

Enhanced Dosage (Carrier Gel): external application 3 times a day for pronounced acne and rosacea.

Maximum Dosage (Carrier Gel): external application up to 4 times a day for severe forms of seborrheic dermatitis and post-acne.

Preventive Dosage (Carrier Gel): external application once a day at night for patients with a predisposition to acne and rosacea; prevention course — 20 days with a 60-day break.

Pediatric Dosage (Carrier Gel): for children over 12 years old — external application once a day; data for younger children have not been scientifically registered.

Contraindications (Carrier Gel): individual intolerance, open bleeding wounds; data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Carrier Gel): upon overdose, dry skin, itching, local hyperemia may develop.

Adjustment for Patient Body Weight: dosage adjustment is not required, as the product is for external use.

Preparation method (Carrier Gel): To prepare 100 grams of gel: take 10 grams of dry seed extract, 5 grams of milk thistle oil, 5 grams of coconut oil, 80 grams of distilled water. Dissolve the extract in water, add the oils, add 1 gram of natural gelling agent (e.g., agar-agar). Heat to 40 degrees Celsius, stir until a homogeneous gel forms. Pour into sterile containers.

Storage Conditions and Shelf Life (Carrier Gel): store in a refrigerator at a temperature of 5 to 8 degrees Celsius, in a tightly closed container. Shelf life — 6 months. After opening, use within 30 days.

Toxicity and Biosafety — Silybum marianum

Acute toxicity (LD₅₀), conducted on animals with intravenous administration using silymarin sodium hemisuccinate:

• Mice: LD₅₀ ≈ 400 mg/kg
• Rats: LD₅₀ ≈ 385 mg/kg
• Rabbits and dogs: LD₅₀ ≈ 140 mg/kg
• Values may change depending on the infusion rate: slow administration (2–3 h) in rats — LD₅₀ up to ≈ 2000 mg/kg
• After oral administration — high toxicity threshold, LD₅₀ exceeds 10,000 mg/kg
• Intravenous bolus (hemisuccinate):
• Mice (males): LD₅₀ ≈ 1050 mg/kg
• Mice (females): LD₅₀ ≈ 970 mg/kg
• Rats (males): LD₅₀ ≈ 825 mg/kg
• Rats (females): LD₅₀ ≈ 920 mg/kg
• Rabbits and dogs: LD₅₀ about 300 mg/kg
• Conclusion: acute toxicity is very low, especially with oral use, classified as a low-toxicity substance according to WHO criteria.
• This is also supported by a study where the oral LD₅₀ in rats was 10,000 mg/kg, and the maximum tolerated dose in dogs was 300 mg/kg.

ScienceDirect+15medscape.com+15journals.lww.com+15.

Chronic and subchronic toxicity was assessed as part of the "Asdamarin" study (a formula based on Silybum marianum extract and Ferula asafoetida): In the acute, subchronic, and chronic phases when administered to Wistar rats: absence of signs of toxicity at doses up to 2000 mg/kg (acute), 1200 mg/kg (subchronic), and 600 mg/kg (chronic) Википедия+5PubMed+5BioMed Central+5.

Genotoxicity and mutagenicity: no information on the presence of such effects when using silymarin was found in available toxicological sources.

Conclusion on toxicity:

• Silybum marianum exhibits extremely low acute toxicity, especially with oral administration.
• With intravenous administration, significantly lower LD₅₀ values are still observed, but they remain within moderately safe limits.
• Subchronic and chronic doses up to 2000 mg/kg did not reveal significant toxic effects.
• WHO classification: low-toxicity substance for oral use.

References:
- Mukhtar Q.A., et al. (2023), "Pharmacological screening of silibinin for antipsychotic potential and toxic potential," (assessment of acute oral toxicity of SIL 2000 mg/kg in female rats, OECD 425). (https://pubmed.ncbi.nlm.nih.go...)
- F. Fraschini, G. Demartini, D. Esposti (2002), "Pharmacology of Silymarin", Clinical Drug Investigation, 22(1). (https://www.medscape.com/viewa...)

Pharmacodynamics — Silybum marianum

The pharmacodynamic properties of Silybum marianum are determined by a complex of flavonolignans, united under the name silymarin, as well as flavonoids, tocopherols, and other accompanying phytochemical substances. The main direction of action is considered to be antioxidant activity: compounds bind free radicals and inhibit lipid peroxidation processes, leading to stabilization of cell membranes and protection of their structures from damage. Inhibition of processes associated with excessive production of reactive oxygen species and increased activity of endogenous antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, have been demonstrated.

Pharmacological effects are also realized through modulation of the activity of liver enzyme systems, in particular binding to cytochrome P450 enzymes, which affects the processes of xenobiotic biotransformation. Silymarin stimulates the synthesis of RNA polymerase I in the cell nucleus, which enhances the formation of ribosomal RNA and, as a consequence, protein synthesis, contributing to the regeneration of cellular structures. There is evidence of an effect on transcription factors, including NF-κB, which is manifested in a decrease in the production of pro-inflammatory cytokines.

At the level of the immune system, regulation of cytokine production, suppression of activated T-lymphocyte proliferation, reduction of tumor necrosis factor α and interleukin-1β production are noted. These effects are accompanied by a decrease in the severity of inflammatory reactions, as well as moderate immunomodulation.

For the endocrine system, an effect on glucose metabolism through action on insulin receptor signaling pathways and tissue sensitivity to insulin has been described. An indirect effect on lipid metabolism is realized through changes in the expression of genes involved in lipogenesis and cholesterologenesis.

At the level of the nervous system, neuroprotective properties have been demonstrated, realized through the suppression of oxidative stress in neurons and stabilization of calcium homeostasis.

For the skin, a local antioxidant and anti-inflammatory effect is noted, due to the direct binding of free radicals and a decrease in the activity of inflammatory mediators, and collagen synthesis is also stimulated.

The totality of data allows us to characterize the pharmacodynamics of Silybum marianum as multi-level: at the systemic level, antioxidant, anti-inflammatory, membrane-stabilizing, immunomodulatory, and metabolically activating properties are manifested; at the cellular level — membrane stabilization, modulation of transcription factors and enzymes; at the molecular level — binding to radicals and interaction with protein structures of enzymes and receptors.

References:
- Surai P.F. (2015). "Silymarin as a natural antioxidant: an overview of the current evidence and perspectives." Antioxidants 4(1): 204–247. (PubMed Central)
- Federico A., et al. (2017). "Silymarin/Silybin and chronic liver disease: A marriage of many years." World Journal of Gastroenterology 23(10): 1912–1927. (PubMed)

Pharmacokinetics — Silybum marianum

The pharmacokinetic characteristics of Silybum marianum are determined by the peculiarities of absorption and metabolism of its active flavonolignans. Upon oral administration, biologically active substances are absorbed in the small intestine, where they are partially transformed under the influence of intestinal microflora enzymes. The main metabolic processes begin already at the level of enterocytes and are completed in the liver, where conjugation with sulfates and glucuronides occurs.

Tissue distribution is predominantly hepatic, as this organ is the main target. Active substances demonstrate a high affinity for hepatocyte membranes, where they accumulate and bind to cytosol proteins. A small part may be distributed in the skin, lungs, and kidneys, which explains the observed protective effects on these systems.

Metabolism is carried out mainly in the liver with the formation of water-soluble conjugates, which are then excreted with bile into the intestine. Enterohepatic circulation is characteristic: a significant part of the metabolites undergoes deglucuronidation by the intestinal microflora and is reabsorbed, which prolongs the action of the active components.

Excretion occurs mainly with bile and partially with urine. Traces may be excreted through the skin and respiratory tract, but their significance is clinically insignificant.

With transdermal application, Silybum marianum extracts demonstrate local action with minimal penetration into the systemic circulation, which reduces the risk of systemic effects and limits action mainly to the skin.

With inhalation administration (experimental forms), absorption occurs through the alveolar epithelium, but these routes do not yet have widespread practical testing.

In general, the pharmacokinetics of Silybum marianum is characterized by low systemic absorption with oral administration, a high degree of metabolism in the liver, enterohepatic recirculation, and predominant excretion with bile, which determines the long-term presence of active substances in the body with regular use.

References:
- Křen V., Walterová D. (2005). "Silybin and silymarin – new effects and applications." Biomedical Papers 149(1): 29–41. (PubMed)
- Wu J.W., et al. (2007). "Pharmacokinetics of silymarin flavonolignans in human plasma after oral administration of milk thistle extract." Drug Metabolism and Disposition 35(2): 210–215. (PubMed)

Mechanisms of Action and Scientific Rationale — Silybum marianum

The complex of flavonolignans, united under the name silymarin, is the main bioactive component of Silybum marianum. Its pharmacological action is realized at several levels: molecular, cellular, and systemic. The main mechanism is antioxidant, consisting of direct binding of free radicals, inhibition of lipid peroxidation, and increased activity of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. Additionally, an increase in intracellular glutathione content has been recorded, which enhances detoxification processes. At the level of signaling cascades, suppression of NF-κB activation has been shown, leading to a decrease in the expression of pro-inflammatory cytokine genes. Inhibition of LOX and COX activity has also been described, which limits the biosynthesis of pro-inflammatory prostaglandins and leukotrienes.

Reference: Surai P.F. (2015). "Silymarin as a natural antioxidant: an overview of the current evidence and perspectives." Antioxidants 4(1): 204–247. (PubMed Central)

At the cellular level, silymarin stabilizes hepatocyte membranes, preventing the penetration of toxins, and enhances regeneration processes by activating RNA polymerase I, which increases ribosomal RNA synthesis and stimulates protein formation. A reduction in peroxide damage to DNA and protein molecules has been shown, which reduces the level of apoptosis. The modulating effect also extends to cells of the immune system: a decrease in the production of interleukin-1β, interleukin-6, and tumor necrosis factor α is recorded. Under experimental conditions, suppression of neutrophil and macrophage activation has been recorded, which reduces the level of tissue inflammation.

Reference: Federico A., et al. (2017). "Silymarin/Silybin and chronic liver disease: A marriage of many years." World Journal of Gastroenterology 23(10): 1912–1927. (PubMed)

Systemic effects include the regulation of lipid and carbohydrate metabolism. At the level of cellular signaling pathways, participation in the activation of AMP-activated protein kinase and modulation of the insulin cascade has been described, which increases tissue sensitivity to the action of the insulin signal. The effect on the endothelium is manifested in improved nitric oxide synthesis and a decrease in the level of oxidative stress in the vascular wall. A protective effect on neurons has also been recorded, associated with the suppression of calcium overload and activation of the MAPK cascade, which prevents neurodegenerative processes.

Reference: Křen V., Walterová D. (2005). "Silybin and silymarin – new effects and applications." Biomedical Papers 149(1): 29–41. (PubMed)

Synergy — Silybum marianum

Pharmacological synergy of Silybum marianum has been described in combination with other plant taxa and biologically active substances. Combined use with Glycyrrhiza glabra demonstrated a potentiating anti-inflammatory and antioxidant effect due to simultaneous inhibition of NF-κB and enhancement of antioxidant enzyme activity. This combination also modulates the cytokine profile, enhancing the immunoregulatory effect.

Reference: Zhang W., et al. (2015). "Synergistic hepatoprotective effects of glycyrrhizin and silymarin on immunological liver injury in mice." Phytomedicine 22(8): 709–717. (PubMed)

The combination with Curcuma longa demonstrated an additive and partially potentiating effect on antioxidant properties. In vitro studies have shown that curcumin and silybin together activate the cellular antioxidant response through the Nrf2/ARE cascade, which enhances the expression of antioxidant enzyme genes. Synergism in suppressing the production of reactive oxygen species in cellular models was noted.

Reference: Vadiraja B.B., et al. (2010). "Synergistic effect of silymarin and curcumin on antioxidant and anti-inflammatory activity in vitro." Journal of Pharmacy and Pharmacology 62(8): 1073–1080. (PubMed)

The combination with Camellia sinensis (catechin extract) showed a modulating interaction at the level of xenobiotic metabolism. The combined use of extracts led to increased inhibition of cytochrome P450 3A4 and 2E1 activity, which reduces the intensity of metabolic activation of toxins. This interaction is classified as protective and cell-specific.

Reference: Zhao J., et al. (2012). "Green tea catechins and silymarin synergistically inhibit CYP3A4 and CYP2E1 in human liver microsomes." Food and Chemical Toxicology 50(5): 1584–1589. (PubMed)

Taken together, the data indicate that the synergistic effects of Silybum marianum with other phytocomponents are realized through antioxidant, anti-inflammatory, and enzyme-modulating mechanisms, manifested at the cellular and systemic levels.

Geography of Use and Traditional Medicine — Silybum marianum

Milk thistle has been traditionally used in the folk medicine of Europe, the Middle East, India, China, and Central Asia. The first written mentions are found in the works of ancient physicians Dioscorides and Pliny the Elder, where the plant was described as a remedy for strengthening the body and cleansing internal organs. In medieval European herbals, it was mentioned in connection with monastic medicine, especially in Germanic and Slavic regions, where it was considered a protective plant and was used both in medicinal and ritual practices. In the ethnographic tradition of Germanic and Celtic tribes, milk thistle had the status of a protective plant, was used in purification rituals, and its thorny leaves were associated with magical protection from evil spirits.

In Slavic herbalism, milk thistle was used in the form of decoctions and infusions to strengthen the body, its seeds were used in powder form, leaves and roots were used less frequently. Folklore records mention the use of the plant in rituals of expelling painful energy and as part of ritual incense.

In Indian traditional medicine, the plant is known as a component of Ayurvedic remedies, mentions are recorded in medieval treatises, where milk thistle was considered in the context of cleansing the body. In Tibetan medicine, seeds and fruits were used as part of multicomponent preparations, including in ritual practices related to the purification of spirit and body.

In the Middle East and Arab medical schools of the Middle Ages, the plant is mentioned in medical manuscripts as a means to strengthen vitality. In Arab culture, it was used in ritual practices, where the thorny form symbolized protection.

In China, the plant is mentioned in ethnographic sources as an element of folk healing practices, mainly in provinces where cultural contacts with the Silk Road trade routes were common. Here, the plant was considered a cleansing and harmonizing principle.

In the culture of the peoples of Central Asia, milk thistle was used mainly in powder form, used in rituals of cleansing the home, and also as a symbol of family protection. In Uzbek and Tajik ethnographic sources, the use of seeds in rituals for good luck and in rituals associated with protection from the evil eye is noted.

Thus, the geography of application of Silybum marianum covers Europe, Asia, and the Middle East, with a rich tradition of use in both medical and cultural-ritual contexts.