Aesculus hippocastanum (Horse Chestnut)

Aesculus hippocastanum (Horse Chestnut)

Product Name: Конский каштан, Aesculus hippocastanum, Gewöhnliche Rosskastanie, Castaño de Indias, Marronnier d'Inde, كستناء الحصان, เกาลัดม้า, Ot kashtani, Ат каштаны, At şabalıdı, Аспи каштан, Paprastasis kaštonas, Parastais zirgkastaņa, Кінський каштан, At şabalıdı, ערמון הסוסים.

Synonyms: Каштан конский обыкновенный, конский каштан обыкновенный, horse chestnut, common horse chestnut, Rosskastanie, Indische Kastanie, castaño loco, marronnier commun, marronnier blanc, كستناء هندي, เกาลัดยุโรป.

Parts Used: seeds, bark, flowers, leaves, pericarps.

Main Indications for Use of Aesculus hippocastanum: Chronic venous insufficiency of the lower extremities, varicose disease of the lower extremities, post-thrombotic syndrome, soft tissue edema of venous origin, hemorrhoids, venous lymphatic insufficiency, capillary toxicosis, orthostatic edema, phlebopathy, chronic lymphedema.

Indications for Use of Aesculus hippocastanum in Mixtures and Complexes: Arterial hypertension, coronary heart disease, atherosclerosis of the arteries of the lower extremities, diabetic angiopathy, trophic ulcers of venous origin, couperose, prostatitis of congestive origin, fibrocystic mastopathy, inflammatory joint diseases, peripheral neuropathy of vascular origin.

Main Pharmacological Properties of Aesculus hippocastanum

Venotonic, angioprotective, anti-edematous, capillary-protective.

Pharmacological Forms:
Powder
Dry Extract
Tincture
Oil Infusion
Ointment
Cream
Rectal Suppositories
Gel for External Use
Solution for External Use
Liniment

Dosage of Pharmaceutical Forms — Aesculus hippocastanum

Powder — Aesculus hippocastanum

Indications (Powder): Chronic venous insufficiency of the lower extremities, varicose disease of the lower extremities, post-thrombotic syndrome, hemorrhoids, venous edema of soft tissues, lymphedema of the lower extremities.

Standard Dosage (Powder): Standardized seed powder, calculated for triterpene saponin content, expressed as escin 50–100 mg per day orally, divided into 2 doses, course duration — 28 days.

Enhanced Dosage (Powder): 120–150 mg of escin per day for pronounced venous edema, post-thrombotic syndrome, prolonged lymphedema, course duration — up to 56 days under tolerance control.

Maximum Dosage (Powder): Up to 180 mg of escin per day short-term for pronounced venous stasis and pain syndrome of venous origin, duration — no more than 14 days.

Preventive Dosage (Powder): 50 mg of escin per day for 21–30 days for chronic venous insufficiency in the compensation stage, during prolonged static load, and with a hereditary predisposition to varicose disease.

Pediatric Dosage (Powder): Use is permitted from 12 years of age with a body weight over 40 kg at a dose of 1 mg of escin per kilogram of body weight per day, divided into 2 doses.

Contraindications (Powder): Individual hypersensitivity, severe renal insufficiency, active gastrointestinal bleeding, coagulopathies, first trimester of pregnancy. Data on contraindications during lactation have not been scientifically registered.

Side Effects (Powder): Dyspepsia, nausea, skin itching, allergic reactions, headache when the dosage is exceeded.

Adjustment for Patient Body Weight (Powder): For body weight below 60 kg — a 20 percent dosage reduction; for body weight above 90 kg — a 15 percent increase is permissible within the maximum dosage.

Preparation Method (Powder): To prepare 100 g of the product, 100 g of dried peeled seeds are used. The seeds are ground to a fine state at a temperature not exceeding 40 degrees Celsius. Sifted through a sieve with a mesh size of 0.5 mm. Stored in an airtight container.

Storage Conditions and Shelf Life (Powder): Store at a temperature of +5 to +20 degrees Celsius in a dry, light-protected place, shielded from electromagnetic radiation, shelf life — 24 months, after opening use within 6 months.

Dry Extract — Aesculus hippocastanum

Indications (Dry Extract): Chronic venous insufficiency of the lower extremities, varicose disease of the lower extremities, post-thrombotic syndrome, venous edema of soft tissues, hemorrhoids, capillary toxicosis, venous lymphatic insufficiency.

Standard Dosage (Dry Extract): Standardized dry seed extract with a content of triterpene saponins expressed as escin 100 mg per day orally, divided into 2 doses, course duration — 28 days.

Enhanced Dosage (Dry Extract): 150 mg of escin per day for pronounced venous edema, lymphedema, post-thrombotic syndrome, course duration — 42–56 days under control of renal function and hemostasis parameters.

Maximum Dosage (Dry Extract): Up to 200 mg of escin per day short-term for pronounced venous stasis and pain syndrome of venous origin, no more than 14 days.

Preventive Dosage (Dry Extract): 50–75 mg of escin per day for 21–30 days for chronic venous insufficiency in the compensation stage, during prolonged upright position, and with a hereditary predisposition to varicose disease.

Pediatric Dosage (Dry Extract): Use is permitted from 12 years of age with a body weight over 40 kg at a dose of 1 mg of escin per kilogram of body weight per day, divided into 2 doses.

Contraindications (Dry Extract): Individual hypersensitivity, severe renal insufficiency, active bleeding, coagulopathies, first trimester of pregnancy. Data on contraindications during lactation have not been scientifically registered.

Side Effects (Dry Extract): Dyspepsia, nausea, epigastric pain, itching, skin rash, headache when the dosage is exceeded.

Adjustment for Patient Body Weight (Dry Extract): For body weight below 60 kg — a 20 percent dosage reduction; for body weight above 90 kg — an increase up to 15 percent is permissible within the maximum dosage.

Preparation Method (Dry Extract): To prepare 100 g of extract, 500 g of crushed dried seeds and 2500 ml of 70 percent ethanol are used. Ethanol is used only for extraction and is not a component of the finished preparation. The raw material is poured with the solvent and infused for 7 days at a temperature of +20...+25 degrees Celsius with daily stirring. After filtration, evaporation is carried out in a water bath at a temperature not exceeding 50 degrees Celsius until complete removal of ethanol. The control sign is the complete disappearance of the solvent odor. The permissible residual ethanol content is no more than 5000 ppm for external forms and no more than 500 ppm for internal use in accordance with pharmacopoeial standards. The intermediate product containing liquid solvent is not permitted for use as a medicinal product. The dry residue is brought to a mass of 100 g.

Storage Conditions and Shelf Life (Dry Extract): Store at a temperature of +5 to +20 degrees Celsius in a dry, light-protected place, in an airtight container, shielded from electromagnetic radiation, shelf life — 36 months, after opening use within 12 months.

Alcohol-Based Tincture — Aesculus hippocastanum

Indications (Tincture): Chronic venous insufficiency of the lower extremities, varicose disease of the lower extremities, hemorrhoids, post-thrombotic syndrome, venous edema of soft tissues, phlebopathy, lymphedema of the lower extremities.

Standard Dosage (Tincture): Tincture of seeds with a raw material concentration of 1:5 in 40 percent ethanol, orally 20–30 drops 2 times a day after meals, course duration — 28 days.

Enhanced Dosage (Tincture): 30–40 drops 2 times a day for pronounced venous edema, post-thrombotic syndrome, course duration — up to 42 days under tolerance control.

Maximum Dosage (Tincture): Up to 50 drops 2 times a day short-term for pronounced venous stasis and pain syndrome of venous origin, no more than 14 days.

Preventive Dosage (Tincture): 15–20 drops 1–2 times a day for 21 days for chronic venous insufficiency in the compensation stage and during prolonged static load.

Pediatric Dosage (Tincture): Internal use of Tincture in childhood is not recommended.

Contraindications (Tincture): Individual hypersensitivity, pregnancy, lactation period, severe hepatic insufficiency, alcoholism, active bleeding, coagulopathies, childhood under 18 years.

Side Effects (Tincture): Nausea, dyspepsia, allergic skin reactions, headache, feeling of heat when the dosage is exceeded.

Adjustment for Patient Body Weight (Tincture): For body weight below 60 kg — a 20 percent dosage reduction; for body weight above 90 kg — an increase up to 10 percent is permissible within the maximum dosage.

Preparation Method (Tincture): To prepare 100 g of tincture, 20 g of crushed dried seeds and 80 g of 40 percent ethanol are used. Ethanol is used only for extraction and is not an active component. The raw material is poured with the solvent and infused for 14 days at a temperature of +20...+25 degrees Celsius in a light-protected place with daily shaking. After infusion, it is filtered. If necessary, the concentration of active substances is adjusted by partial evaporation in a water bath at a temperature not exceeding 50 degrees Celsius. The control sign of removal of excess solvent is the absence of a sharp alcohol odor. The residual ethanol content must comply with pharmacopoeial standards for internal use. The intermediate product containing a high concentration of solvent is not used as a medicinal product.

Storage Conditions and Shelf Life (Tincture): Store at a temperature of +5 to +20 degrees Celsius in a tightly closed, light-protected container, shielded from electromagnetic radiation, shelf life — 24 months, after opening use within 6 months.

Oil Infusion — Aesculus hippocastanum

Indications (Oil Infusion): Varicose disease of the lower extremities, chronic venous insufficiency of the lower extremities, external hemorrhoids, lymphedema, soft tissue edema of venous origin, couperose.

Standard Dosage (Oil Infusion): Apply topically in a thin layer to the affected area 2 times a day, course duration — 21–30 days.

Enhanced Dosage (Oil Infusion): Apply 3 times a day for pronounced venous edema and lymphedema, course — up to 42 days.

Maximum Dosage (Oil Infusion): Up to 4 applications a day short-term for pronounced stasis and pain syndrome of venous origin, no more than 14 days.

Preventive Dosage (Oil Infusion): 1–2 applications a day for 21 days for chronic venous insufficiency in the compensation stage and during prolonged static load.

Pediatric Dosage (Oil Infusion): Topical use is permitted from 7 years of age in the absence of skin damage, 1–2 times a day.

Contraindications (Oil Infusion): Individual hypersensitivity, violation of skin integrity, weeping dermatoses. Data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Oil Infusion): Contact dermatitis, itching, skin redness in case of individual sensitivity.

Adjustment for Patient Body Weight (Oil Infusion): No adjustment for body weight is required for topical use.

Preparation Method (Oil Infusion): To prepare 100 g of the product, 20 g of crushed dried seeds and 80 g of refined coconut oil are used. The mixture is placed in a water bath at a temperature up to 50 degrees Celsius and kept for 3 hours with periodic stirring. After cooling, it is filtered through gauze. The finished product is brought to a mass of 100 g with coconut oil.

Storage Conditions and Shelf Life (Oil Infusion): Store at a temperature of +5 to +15 degrees Celsius in a dark place, in an airtight container, shelf life — 12 months, after opening use within 3 months.

Ointment — Aesculus hippocastanum

Indications (Ointment): Varicose disease of the lower extremities, chronic venous insufficiency of the lower extremities, external hemorrhoids, lymphedema, soft tissue edema of venous origin, post-traumatic soft tissue edema, couperose.

Standard Dosage (Ointment): Apply topically in a thin layer to the affected area 2 times a day, course duration — 21–30 days.

Enhanced Dosage (Ointment): Apply 3 times a day for pronounced venous edema and lymphedema, course — up to 42 days.

Maximum Dosage (Ointment): Up to 4 applications a day short-term for pronounced stasis and pain syndrome of venous origin, no more than 14 days.

Preventive Dosage (Ointment): 1–2 applications a day for 21 days for chronic venous insufficiency in the compensation stage and during prolonged static load.

Pediatric Dosage (Ointment): Topical use is permitted from 7 years of age in the absence of skin damage, 1–2 times a day.

Contraindications (Ointment): Individual hypersensitivity, violation of skin integrity, weeping dermatoses. Data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Ointment): Contact dermatitis, itching, skin hyperemia in case of individual sensitivity.

Adjustment for Patient Body Weight (Ointment): No adjustment for body weight is required for topical use.

Preparation Method (Ointment): To prepare 100 g of ointment, 10 g of dry seed extract, 70 g of refined coconut oil, and 20 g of beeswax are used. The oil is heated in a water bath at a temperature not exceeding 50 degrees Celsius, and wax is added until completely dissolved. The dry extract is introduced into the mixture at a temperature not exceeding 40 degrees Celsius, thoroughly mixed until a homogeneous mass is obtained. After cooling, it is packaged into sterile containers.

Storage Conditions and Shelf Life (Ointment): Store at a temperature of +5 to +15 degrees Celsius in a light-protected place, in an airtight container, shelf life — 12 months, after opening use within 3 months.

Cream — Aesculus hippocastanum

Indications (Cream): Varicose disease of the lower extremities, chronic venous insufficiency of the lower extremities, couperose, soft tissue edema of venous origin, post-traumatic soft tissue edema, external hemorrhoids.

Standard Dosage (Cream): Apply topically 2 times a day to cleansed skin, course — 21–30 days.

Enhanced Dosage (Cream): 3 applications a day for pronounced venous edema and stasis, course — up to 42 days.

Maximum Dosage (Cream): Up to 4 applications a day short-term for pronounced pain syndrome of venous origin, no more than 14 days.

Preventive Dosage (Cream): 1–2 applications a day for 21 days for chronic venous insufficiency in the compensation stage.

Pediatric Dosage (Cream): Topical use is permitted from 7 years of age in the absence of skin damage, 1–2 times a day.

Contraindications (Cream): Individual hypersensitivity, open wounds, weeping dermatoses. Data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Cream): Local allergic reactions, itching, skin redness.

Adjustment for Patient Body Weight (Cream): No adjustment for body weight is required for topical use.

Preparation Method (Cream): To prepare 100 g of cream, 5 g of dry seed extract, 60 g of refined coconut oil, 5 g of beeswax, and 30 g of purified water are used. The oil and wax are heated in a water bath at a temperature up to 50 degrees Celsius. In a separate container, water is heated to a temperature of +36...+38 degrees Celsius. The aqueous phase is slowly introduced into the oil phase with constant stirring until an emulsion is formed. At a temperature not exceeding 40 degrees Celsius, the dry extract is added, mixed until homogeneous, and packaged.

Storage Conditions and Shelf Life (Cream): Store at a temperature of +5 to +10 degrees Celsius in a light-protected place, shelf life — 6 months, after opening use within 2 months.

Rectal Suppositories — Aesculus hippocastanum

Indications (Rectal Suppositories): Internal hemorrhoids, combined hemorrhoids, anal fissure, non-ulcerative proctitis, venous stasis in the lesser pelvis.

Standard Dosage (Rectal Suppositories): 1 suppository 1–2 times a day after hygiene procedures, course duration — 14 days.

Enhanced Dosage (Rectal Suppositories): 1 suppository 2 times a day for pronounced pain syndrome and venous stasis, course — up to 21 days.

Maximum Dosage (Rectal Suppositories): 1 suppository 3 times a day short-term for pronounced inflammatory process of venous origin, no more than 7 days.

Preventive Dosage (Rectal Suppositories): 1 suppository once a day for 10–14 days for chronic hemorrhoids in the remission stage and with a tendency to venous stasis.

Pediatric Dosage (Rectal Suppositories): Use is not recommended in childhood under 18 years.

Contraindications (Rectal Suppositories): Individual hypersensitivity, active rectal bleeding, ulcerative lesions of the rectum, coagulopathies. Data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Rectal Suppositories): Burning at the site of administration, itching, local allergic reactions in case of individual sensitivity.

Adjustment for Patient Body Weight (Rectal Suppositories): No adjustment for body weight is required.

Preparation Method (Rectal Suppositories): To prepare 100 g of the base, 90 g of cocoa butter and 10 g of dry seed extract are used. Cocoa butter is melted in a water bath at a temperature not exceeding 40 degrees Celsius. The dry extract is introduced into the melted base with constant stirring until uniform distribution. The mass is poured into molds of 2 g and cooled until completely solidified.

Storage Conditions and Shelf Life (Rectal Suppositories): Store at a temperature of +5 to +10 degrees Celsius in a light-protected place, shelf life — 12 months, after opening the blister use within 30 days.

Gel for External Use — Aesculus hippocastanum

Indications (Gel for External Use): Varicose disease of the lower extremities, chronic venous insufficiency of the lower extremities, soft tissue edema of venous origin, post-traumatic soft tissue edema, couperose, lymphedema.

Standard Dosage (Gel for External Use): Apply in a thin layer 2 times a day to intact skin, course — 21–30 days.

Enhanced Dosage (Gel for External Use): 3 applications a day for pronounced venous stasis and edema, course — up to 42 days.

Maximum Dosage (Gel for External Use): Up to 4 applications a day short-term for pronounced pain syndrome of venous origin, no more than 14 days.

Preventive Dosage (Gel for External Use): 1–2 applications a day for 21 days for chronic venous insufficiency in the compensation stage.

Pediatric Dosage (Gel for External Use): Use is permitted from 7 years of age in the absence of skin damage, 1–2 times a day.

Contraindications (Gel for External Use): Individual hypersensitivity, open wounds, weeping dermatoses. Data on contraindications during pregnancy and lactation have not been scientifically registered.

Side Effects (Gel for External Use): Local allergic reactions, itching, skin redness.

Adjustment for Patient Body Weight (Gel for External Use): No adjustment is required.

Preparation Method (Gel for External Use): To prepare 100 g of gel, 5 g of dry seed extract, 2 g of a plant-derived carbomer base, 70 g of purified water, 20 g of coconut oil, and 3 g of glycerin are used. Water is heated to a temperature of +36...+38 degrees Celsius, and carbomer is introduced with stirring until swelling. Separately, coconut oil is heated to 40 degrees Celsius and introduced into the aqueous phase with intensive stirring. Dry extract and glycerin are added, and the mass is brought to homogeneity.

Storage Conditions and Shelf Life (Gel for External Use): Store at a temperature of +5 to +10 degrees Celsius in a light-protected place, shelf life — 6 months, after opening use within 2 months.

Toxicity and Biosafety — Aesculus hippocastanum

According to experimental studies, the acute toxicity of the aqueous-alcoholic extract of Aesculus hippocastanum seeds in rats with oral administration is characterized by an LD50 value in the range of 1000–1500 mg/kg body weight calculated as an extract containing triterpene saponins, including escin. With intravenous administration of purified escin, the LD50 in laboratory animals is lower and amounts to about 3–10 mg/kg body weight, which is associated with the direct hemolytic action of saponins with parenteral administration. In chronic toxicity studies with oral administration of standardized seed extracts at therapeutic doses, no irreversible morphological changes in the liver and kidneys were detected. Reversible dyspeptic phenomena and moderate irritating action on the gastrointestinal mucosa were noted when the dosage was exceeded. Data on genotoxicity and mutagenicity of seed extracts in standard in vitro test systems did not reveal mutagenic potential at therapeutic concentrations. In accordance with the World Health Organization classification by the level of acute toxicity with oral use, the standardized seed extract belongs to the category of low-toxicity substances when recommended dosages are observed. Particular caution should be exercised in cases of renal dysfunction and a tendency to bleeding due to the moderate anticoagulant action.

Reference: Sirtori C.R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacological Research, 44(3), 183–193. https://pubmed.ncbi.nlm.nih.go...

Pharmacodynamics — Aesculus hippocastanum

The pharmacodynamic activity of Aesculus hippocastanum is determined primarily by a complex of triterpene saponins collectively known as escin, as well as flavonoids, coumarins, and proanthocyanidins. The main direction of action is the effect on the venous wall and the microcirculatory bed. Escin increases the tone of the venous wall through modulation of ion fluxes in vascular smooth muscle cells and enhancement of the contractile activity of veins, which is accompanied by a decrease in venous capacity and a reduction in stasis phenomena.

At the endothelial level, stabilization of cell membranes and a decrease in capillary permeability are noted. This effect is associated with inhibition of the activity of lysosomal enzymes and a decrease in the release of proteolytic factors that damage the basement membrane of vessels. Simultaneously, the release of inflammatory mediators, including prostaglandins and pro-inflammatory cytokines, is suppressed, which is realized through influence on signaling cascades regulating the expression of inflammatory response mediators.

The anti-exudative effect is manifested by a decrease in plasma filtration through the vascular wall and a reduction in interstitial edema. This is accompanied by normalization of lymphatic drainage due to increased tone of lymphatic vessels and enhancement of their pumping function.

The antioxidant component of the action is due to the presence of flavonoids and proanthocyanidins capable of neutralizing reactive oxygen species and reducing the severity of oxidative stress in endothelial cells. This helps protect the vascular wall from structural damage and maintain its functional integrity.

Additionally, a moderate antiplatelet effect has been described, associated with a decrease in platelet aggregation and modulation of thromboxane synthesis. The complex effect on the vascular wall, endothelium, and microcirculation forms the angioprotective profile of Aesculus hippocastanum, realized both with systemic and local application.

References:
Sirtori C.R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacological Research, 44(3), 183–193. https://pubmed.ncbi.nlm.nih.go...
WHO (2002). WHO Monographs on Selected Medicinal Plants. Volume 2: Aesculus hippocastanum. World Health Organization. https://apps.who.int/iris/handle/10665/42052

Pharmacokinetics — Aesculus hippocastanum

With oral administration of standardized seed extracts of Aesculus hippocastanum, the absorption of triterpene saponins occurs primarily in the small intestine. Saponins have an amphiphilic structure, which determines their partial hydrolyzability under the action of intestinal microflora with the formation of more lipophilic metabolites. Bioavailability with oral administration is limited due to the relatively large molecular weight of saponins and their tendency to form complexes with food components.

After absorption, active components are distributed primarily in the vascular wall and tissues rich in the microcirculatory bed. Binding to plasma proteins is noted, which ensures gradual release of active substances and a prolonged vascular effect.

Metabolism occurs primarily in the liver with the participation of enzyme biotransformation systems, including oxidative and conjugation reactions. The resulting metabolites are characterized by greater hydrophilicity and are excreted mainly by the kidneys in urine, partially with bile through the intestine.

With external application (ointment, cream, gel, oil infusion), the penetration of active components occurs transdermally through the stratum corneum of the epidermis. Lipophilic fractions, including saponins and flavonoids, partially accumulate in the surface layers of the skin and subcutaneous tissue, providing a local effect without significant systemic exposure. Systemic absorption with external application is minimal provided the integrity of the skin is preserved.

With rectal administration of suppositories, active components are absorbed through the venous plexus of the rectum, partially bypassing primary hepatic metabolism, which contributes to a more rapid onset of the local venotonic effect.

Coumarins and flavonoids contained in seeds and bark undergo further biotransformation.

References:
Sirtori C.R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacological Research, 44(3), 183–193. https://pubmed.ncbi.nlm.nih.go...
WHO (2002). WHO Monographs on Selected Medicinal Plants. Volume 2: Aesculus hippocastanum. World Health Organization. https://apps.who.int/iris/handle/10665/42052

Mechanisms of Action and Scientific Rationale — Aesculus hippocastanum

The pharmacological activity of Aesculus hippocastanum is determined primarily by a complex of triterpene saponins collectively known as escin, as well as flavonoids and coumarins. At the cellular level, escin interacts with the membrane structures of endothelial cells, stabilizing the phospholipid layer and reducing the activity of lysosomal enzymes, including hyaluronidase and elastase. This leads to a decrease in the degradation of extracellular matrix components and a reduction in capillary wall permeability.

The anti-inflammatory mechanism is associated with modulation of the synthesis of pro-inflammatory mediators. In experimental models, it has been shown that escin reduces the expression of pro-inflammatory cytokines and decreases the formation of prostaglandins by inhibiting the activity of the cyclooxygenase cascade. Additionally, an effect on signaling pathways regulating the transcription of inflammatory response genes has been described, including cascades controlling nuclear inflammatory factors and mitogen-activated protein kinases. This is accompanied by a decrease in neutrophil activation and reduced leukocyte adhesion to the endothelium.

The venotonic effect is realized through increased sensitivity of venous smooth muscle cells to endogenous catecholamines and enhanced contractile activity of the venous wall. The participation of calcium ion channels in smooth muscle cells is assumed, which contributes to an increase in intracellular calcium concentration and increased vascular tone.

The anti-exudative effect is associated with a decrease in plasma filtration through the vascular wall and a reduction in the formation of interstitial edema. The effect on lymphatic vessels is expressed in an increase in their contractile activity and normalization of lymphatic outflow.

Flavonoids contained in the plant realize antioxidant action by neutralizing reactive oxygen species and suppressing lipid peroxidation. This helps protect the endothelium from oxidative damage and maintain the functional integrity of the vascular wall. Coumarins have a mild antiplatelet effect, influencing platelet activation mechanisms and reducing the severity of microcirculatory disorders.

The complex effect on the endothelium, vascular smooth muscle cells, inflammatory enzyme systems, and oxidative status forms the scientifically substantiated angioprotective profile of Aesculus hippocastanum, confirmed by data from experimental and clinical studies.

Reference:
Sirtori C.R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacological Research, 44(3), 183–193. https://pubmed.ncbi.nlm.nih.go...
WHO (2002). WHO Monographs on Selected Medicinal Plants. Volume 2: Aesculus hippocastanum. World Health Organization. https://apps.who.int/iris/handle/10665/42052

Synergy — Aesculus hippocastanum

The pharmacological synergy of Aesculus hippocastanum is most pronounced when combined with plant taxa possessing angioprotective, anti-inflammatory, and antioxidant action. The combination of Aesculus hippocastanum with Vitis vinifera demonstrates an additive and potentiating effect with respect to endothelial stabilization and reduction of capillary permeability. Grapevine proanthocyanidins enhance the antioxidant protection of the vascular wall, while escin saponins modulate venous tone and reduce exudation, which forms tissue-specific synergy at the level of the microcirculatory bed.

Reference: Sirtori C.R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacological Research, 44(3), 183–193. https://pubmed.ncbi.nlm.nih.go...

The combination of Aesculus hippocastanum with Ruscus aculeatus is characterized by potentiation of the venotonic effect. Steroid saponins of Ruscus aculeatus enhance the contraction of venous smooth muscle cells through adrenergic mechanisms, while escin reduces vascular wall permeability and the inflammatory response. The combined influence on receptor mechanisms of vascular regulation and inflammatory mediators forms a pronounced modulating effect on venous hemodynamics.

Reference: WHO (2002). WHO Monographs on Selected Medicinal Plants. Volume 2. World Health Organization. https://apps.who.int/iris/handle/10665/42052

An additive antioxidant and capillary-protective effect has been described with the combination of Aesculus hippocastanum with Ginkgo biloba. Flavonol glycosides of Ginkgo biloba reduce platelet aggregation and suppress the formation of free radicals, while escin stabilizes endothelial membranes and reduces exudation. The proposed mechanism of synergy is associated with a simultaneous effect on redox processes and regulation of vascular tone.

Reference: Kleijnen J., Knipschild P. (1992). Ginkgo biloba. British Journal of Clinical Pharmacology, 34(4), 352–358. https://pubmed.ncbi.nlm.nih.gov/1330153/

Functional synergy is also observed when combined with Centella asiatica, where triterpenoids of Centella asiatica promote remodeling of the connective tissue of the vascular wall and stimulate collagen synthesis. In combination with escin, a protective effect is formed with respect to the extracellular matrix and the basement membrane of vessels.

Reference: Chemical, pharmacological and clinical profile of Centella asiatica. Phytomedicine, 7(5), 427–448. https://pubmed.ncbi.nlm.nih.gov/11081982/

Thus, Aesculus hippocastanum demonstrates scientifically substantiated pharmacological synergy with angioprotective and antioxidant plants, realized through additive and potentiating mechanisms at the level of the endothelium, inflammatory mediators, and vascular smooth muscle cells.

Geography of Use and Traditional Medicine — Aesculus hippocastanum

Aesculus hippocastanum originates from the Balkan region, where its natural range covers the territories of modern Greece, North Macedonia, Albania, and Bulgaria. The plant was introduced to Europe in the 16th century through the Ottoman Empire, after which it spread widely in Central and Western Europe as an ornamental and medicinal tree. Already in the herbals of the 17th–18th centuries in Germany and France, the use of seeds and bark in folk medicine for conditions associated with impaired venous circulation is mentioned.

In the traditional medicine of Central Europe, seeds were crushed and used in the form of infusions and rubs for external use. Flowers and bark were used in the form of aqueous extracts. In Slavic folk practices, the chestnut was considered a "tree of strength," its fruits were worn as a talisman against "evil energy" and the evil eye. In a number of regions of Eastern Europe, chestnuts were placed in the home or in clothing pockets as a symbol of protection and stabilization of vital energy.

In the Ottoman tradition, the plant was used primarily in veterinary practice, from which the European name associated with its use in horse diseases originated. Subsequently, the knowledge was adapted for human medicine.

In the folk medicine of France and Germany, chestnut was used in the form of compresses and lotions. In the Balkan countries, practices of preparing alcohol extracts for rubbing are known. In the cultural context, the plant was associated with endurance and resistance, which was symbolically linked to its effect on the vascular system.

Ethnobotanical sources record the use of Aesculus hippocastanum predominantly in the European region. Reliable data on wide use in traditional medical systems of Asia, such as Chinese or Indian classical medicine, have not been recorded.