​Maclura pomifera (Osage Orange)

Maclura pomifera (Osage Orange)

Product Name: Маклюра оранжевая, Maclura pomifera, Osagedorn, Naranjo de los osages, Maclure, مكليورا برتقالية, มะคูร่า โพมิฟีร่า

Synonyms: маклюра яблокообразная, адамово яблоко, китайский апельсин, лжеапельсин, osage orange, hedge apple, horse apple, bois d’arc, Apfel der Osagen, naranja de los osages, naranja de caballo, pomme de cheval, orange des osages, تفاحة الخيل, البرتقال الكاذب, ส้มปลอม, ผลไม้ของม้า, มะคูร่าออเรนจ์

Parts Used: fruits, leaves, bark, wood, milky sap.

Main Indications for Use of Maclura pomifera: Osteoarthritis, osteochondrosis, rheumatoid arthritis, deforming spondylosis, varicose veins of the lower extremities, thrombophlebitis, benign prostatic hyperplasia, uterine fibroids, mastopathy, prostate adenoma, adnexitis, chronic prostatitis, neuropathic pain, trigeminalgia, facial nerve neuralgia, intercostal neuralgia, postherpetic neuralgia, epidermal and dermal angiomatosis, basal cell skin cancer (as part of supportive therapy), chronic forms of dermatitis, psoriasis.

Use of Maclura pomifera in mixtures and complexes: Malignant neoplasms of the liver, pancreas, and lungs, multiple myeloma, systemic lupus erythematosus, Sjögren's syndrome, multiple sclerosis, autoimmune thyroiditis, chronic pancreatitis, chronic hepatitis B and C, endometrial hyperplasia, chronic bronchitis, allergic dermatitis.

Pharmacological Properties of Maclura pomifera: antioxidant, antitumor, immunomodulatory, phytoestrogenic, antimicrobial, anti-inflammatory, analgesic, antifungal, vascular-strengthening, radioprotective, hepatoprotective, antiproliferative.

Dosage of Pharmaceutical Forms — Maclura pomifera

Powder — Maclura pomifera

Indications (Powder): Osteoarthritis, rheumatoid arthritis, osteochondrosis, chronic prostatitis, benign prostatic hyperplasia, uterine fibroids, mastopathy, chronic adnexitis, intercostal neuralgia, postherpetic neuralgia, neuropathic pain, chronic dermatoses, psoriasis.

Standard Dosage (Powder): 2 grams of powder 2 times a day after meals, with warm water. Duration of the course — 30 days.

Enhanced Dosage (Powder): 3 grams 2 times a day for 20 days. Recommended for pronounced pain syndrome against the background of degenerative-dystrophic diseases of the spine, adenomatous changes in the prostate gland, as well as in the complex therapy of benign neoplasms.

Maximum Dosage (Powder): 4 grams 2 times a day. Used only under specialist supervision for pronounced inoperable fibromatoses, multi-organ nodular formations, and chronic neuropathic pain resistant to standard therapy.

Preventive Dosage (Powder): 1 gram per day in the morning with meals, for 21 days, 3 courses per year. Recommended for patients with chronic forms of arthroses, a tendency to benign hyperplasias, perimenopausal women, and men over 45 years of age.

Pediatric Dosage (Powder): Not recommended for children under 12 years of age. From 12 years of age — no more than 500 milligrams per day with body weight not less than 40 kg. Only as prescribed by a specialist. Data on use in younger children and pregnant women are absent.

Contraindications (Powder): Acute liver diseases, pregnancy, lactation period, age under 12 years, individual intolerance. Data on contraindications during lactation, pregnancy, and childhood under 12 years of age have not been scientifically registered.

Side Effects (Powder): With overdose, nausea, bitterness in the mouth, headache, moderate arterial hypotension, irritation of the gastric mucosa have been registered.

Adjustment for Patient Body Weight: For patients with body weight less than 60 kg, a reduction of dosage by 25% is recommended. For body weight above 90 kg, an increase of dosage by 20% is possible, but not above the maximum permissible.

Preparation Method (Powder): To obtain 100 grams of powder, ripe fruits of maclura peeled from the skin are used. The raw material is cut into thin slices and dried in a dehydrator at a temperature of 42–45 degrees Celsius for 36–48 hours. After drying, grinding is carried out in a mortar or mill to a fine powder state. The resulting substance is sieved through a 0.5 mm sieve and packaged in an airtight container.

Storage Conditions and Shelf Life (Powder): Store in a hermetically closed glass container in a dry, light-protected place at a temperature from 5 to 25 degrees Celsius. Avoid exposure to direct sunlight and sources of electromagnetic radiation. Shelf life — 12 months. After opening the package, use within 30 days.

Dry Extract — Maclura pomifera

Indications (Dry Extract): Rheumatoid arthritis, osteoarthritis, benign prostatic hyperplasia, uterine fibroids, adnexitis, mastopathy, facial nerve neuralgia, psoriasis, chronic prostatitis, basal cell skin cancer (as part of supportive therapy).

Standard Dosage (Dry Extract): 250 milligrams of dry extract 2 times a day orally after meals, with warm water. Duration of the course — 30 days.

Enhanced Dosage (Dry Extract): 400 milligrams 2 times a day. Prescribed for the active form of fibromatosis, clinically pronounced hyperplastic process in soft tissues, as well as for prolonged forms of chronic prostatitis and adnexitis.

Maximum Dosage (Dry Extract): 500 milligrams 2 times a day for no more than 10 days consecutively. Used when rapid anti-inflammatory and anti-edematous action is necessary against the background of pronounced nodular processes and pain syndrome.

Preventive Dosage (Dry Extract): 100 milligrams once a day with meals, in 20-day courses 3 times a year. Recommended for a tendency to cystic formations of the mammary glands and ovaries, chronic venous insufficiency, men at risk of prostate hyperplasia after 50 years of age.

Pediatric Dosage (Dry Extract): Use in children under 12 years of age is not recommended. From 12 years of age — no more than 100 milligrams once a day with body weight from 40 kg. Use only as prescribed by a specialist. Data on use in pediatrics and in pregnant women have not been registered.

Contraindications (Dry Extract): Pregnancy, lactation, age under 12 years, acute liver and kidney diseases, individual intolerance. During pregnancy, lactation, and childhood under 12 years of age, contraindications have not been scientifically established, so caution and medical supervision are required.

Side Effects (Dry Extract): In the scientific literature, with exceeding the dose, the following have been recorded: dizziness, dyspepsia, feeling of heaviness in the epigastric region, urticaria-type rash.

Adjustment for Patient Body Weight: For patients with body weight less than 60 kg, a dosage of 75–80% of the standard is recommended. For weight above 90 kg, an increase of the daily dose by 15–20% is permissible while maintaining the frequency of intake.

Preparation Method (Dry Extract): To prepare 100 grams of dry extract, 500 grams of fresh fruits are used. The fruits are cleaned, ground, poured with 70% ethyl alcohol in a ratio of 1:5 and infused for 5 days at a temperature of 25–28 degrees Celsius with periodic stirring. After that, the mass is filtered, evaporated at a temperature not exceeding 45 degrees Celsius in a vacuum evaporator to a viscous mass, and dried lyophilically to a powder state.

Storage Conditions and Shelf Life (Dry Extract): Store in an airtight container made of darkened glass or porcelain at a temperature from 5 to 20 degrees Celsius, in a light-protected place. Avoid contact with metal packaging. Shelf life — 24 months. After opening the package, use within 30 days.

Alcohol Tincture — Maclura pomifera

Indications (Alcohol Tincture): Benign prostatic hyperplasia, uterine fibroids, mastopathy, osteochondrosis, spondyloarthrosis, chronic prostatitis, trigeminal neuralgia, intercostal neuralgia, chronic forms of adnexitis, psoriasis, varicose veins of the lower extremities.

Standard Dosage (Alcohol Tincture): 15 drops 2 times a day 30 minutes before meals, diluted in 30 ml of water. Duration of the course — 30 days.

Enhanced Dosage (Alcohol Tincture): 25 drops 2 times a day, course — 21 days. Used for pronounced manifestations of neuropathic pain syndrome, nodular forms of fibroids, and the active phase of prostatitis with an accompanying pain component.

Maximum Dosage (Alcohol Tincture): 30 drops 2 times a day for no more than 10 days consecutively. Used for multiple joint lesions, painful fibrous nodes, and the active phase of chronic neuritis.

Preventive Dosage (Alcohol Tincture): 10 drops once a day in the morning on an empty stomach, diluted in 20 ml of water. Recommended for patients with an established diagnosis of chronic venous insufficiency, a tendency to nodular formations in the mammary glands, and men over 50 years of age at risk of developing prostatic hyperplasia. Preventive course — 20 days, repeat 3 times a year.

Pediatric Dosage (Alcohol Tincture): Not recommended for children under 18 years of age due to ethanol content. Clinical data on use in children are absent.

Contraindications (Alcohol Tincture): Pregnancy, lactation, childhood under 18 years of age, chronic alcoholism, epilepsy, severe forms of hepatic insufficiency. Data on teratogenicity are absent, but due to the alcohol nature, the tincture is not recommended in these conditions.

Side Effects (Alcohol Tincture): With overdose, dizziness, feeling of heat, facial redness, dyspepsia, short-term decrease in blood pressure are possible. In isolated cases — allergic-type rash.

Adjustment for Patient Body Weight: For patients with weight less than 50 kg — a reduction of dosage by 20%. For patients with weight above 90 kg — an increase of the single dose by 5 drops is permissible, but not more than 30 drops per intake.

Preparation Method (Alcohol Tincture): To prepare 100 ml of alcohol tincture, 100 grams of fresh maclura fruits cut into thin plates are used. The raw material is poured with 70 ml of 70% ethanol and 30 ml of purified water. The container is hermetically closed and infused in a dark place at a temperature of 22–25 degrees Celsius for 14 days with daily shaking. At the end of infusion, the solution is filtered through paper filter and stored in dark glass containers.

Storage Conditions and Shelf Life (Alcohol Tincture): Store in a cool dark place at a temperature from 5 to 18 degrees Celsius in an airtight dark glass bottle. Do not allow exposure to direct light and heating. Avoid contact with metal lids. Shelf life — up to 24 months. After opening the package, use within 60 days.

Oil Infusion — Maclura pomifera

Indications (Oil Infusion): Neuropathic pain, intercostal neuralgia, rheumatoid arthritis, osteochondrosis, psoriasis, chronic dermatitis, basal cell skin carcinoma (in complex therapy), soft tissue fibromatosis, hyperpigmentation, localized vascular network.

Standard Dosage (Oil Infusion): Topically 2 times a day: apply a thin layer to the affected area with massaging movements until absorbed. Course — 14–21 days.

Enhanced Dosage (Oil Infusion): Up to 3 times a day, for dense nodular formations, painful inflammatory foci in joints, projections of spinal nerves. Duration — up to 21 days.

Maximum Dosage (Oil Infusion): Up to 4 times a day on limited skin areas. Used in short courses (no more than 10 days consecutively) for pronounced pain syndrome, psoriatic plaques, periarticular edema.

Preventive Dosage (Oil Infusion): Once a day in the evening on areas prone to chronic inflammation or trophic changes (knees, lower back, neck). Preventive course — 14 days, repeat 2–3 times a year. Recommended for elderly patients with chronic venous insufficiency, deforming osteoarthritis, women with mastopathy.

Pediatric Dosage (Oil Infusion): Use is allowed in children from 7 years of age only on limited skin areas (no more than 3×3 cm), no more than once a day. Body weight — from 25 kg. Skin sensitivity is taken into account. Not used in younger children due to the risk of photosensitization.

Contraindications (Oil Infusion): Open wounds, eczematous skin lesions, allergic reaction to components, age under 7 years. Data on contraindications during pregnancy and lactation have not been registered, so topical use is possible only under medical supervision.

Side Effects (Oil Infusion): Skin irritation, burning, allergic rash, increased itching in application areas with hypersensitivity. Isolated cases of photodermatitis have been recorded.

Adjustment for Patient Body Weight: Dose adjustment is not required, but with body weight less than 50 kg, it is recommended to reduce the application area. With weight more than 90 kg, application to larger areas is permissible, but not more than 25% of the body surface per day.

Preparation Method (Oil Infusion): To prepare 100 grams of oil infusion, take 40 grams of fresh ground maclura fruits and 60 grams of base organic oil (grape seed oil or sesame oil). Place the ground fruits in a glass jar, pour with oil, close tightly. Infuse in a water bath at a temperature of 40–45 degrees Celsius for 4 hours. Then cool, strain through cotton cloth, squeeze out the residues. Store in a dark glass container.

Storage Conditions and Shelf Life (Oil Infusion): Store at a temperature from 5 to 15 degrees Celsius in an airtight dark glass container, away from light, heat, and electromagnetic fields. Shelf life — 6 months. After opening, use within 30 days.

CO2 Extract — Maclura pomifera

Indications (CO2 Extract): Basal cell skin cancer (as part of supportive therapy), hyperpigmentation, chronic psoriasis, age-related skin changes, neurodermatitis, seborrheic dermatitis, angiomatosis, superficial skin neoplasms, skin fibrosis, couperose, decreased skin elasticity, impaired skin barrier.

Standard Dosage (CO2 Extract): Topically once a day, 2–3 drops per 1 cm² of affected skin. Duration of the course — 21 days.

Enhanced Dosage (CO2 Extract): 2 times a day, 3–5 drops on affected areas, especially for pronounced keratosis, fibrosis, senile xanthomas, and vascular asterisks. Course — 14 days.

Maximum Dosage (CO2 Extract): Up to 5 times a day, pointwise, no more than 10 drops per single application. Used for rigid epidermal thickenings, senile plaques, and as part of an intensive skin remodeling program (under specialist supervision).

Preventive Dosage (CO2 Extract): Once a day, 1–2 drops on areas with signs of aging, vascular disorders, or hyperpigmentation. Course — 14 days, repeat 3 times a year. Suitable for the prevention of age-related skin changes in patients over 40 years of age.

Pediatric Dosage (CO2 Extract): Not recommended for children under 14 years of age. From 14 years of age, use is possible for localized forms of acne and seborrheic dermatitis, 1 drop once a day. Use only under dermatologist supervision.

Contraindications (CO2 Extract): Pregnancy, lactation, age under 14 years, open ulcerative skin lesions, individual intolerance. Data on safety during pregnancy and lactation have not been registered.

Side Effects (CO2 Extract): Contact dermatitis, peeling, burning sensation, and skin hyperemia in case of overdose have been registered. In some cases — photosensitization.

Adjustment for Patient Body Weight: Dosage adjustment is not required; however, with weight less than 50 kg, it is recommended to reduce the frequency of use (no more than once a day). With body weight above 90 kg, an increase in the application area is permissible.

Preparation Method (CO2 Extract): To obtain 100 grams of CO2 extract, 1.5 kilograms of ground maclura fruits are used. Extraction is carried out with supercritical carbon dioxide at a temperature of 32–38 degrees Celsius and a pressure of 300 atmospheres for 3 hours. The resulting extract is purified from waxes, then packaged in glass ampoules or vials. The method requires industrial equipment.

Storage Conditions and Shelf Life (CO2 Extract): Store in a dark airtight glass container at a temperature from 4 to 8 degrees Celsius. Avoid heating and direct sunlight. Shield from EMI sources. Shelf life — 24 months. After opening, use within 60 days.

Ethylene/Acetone Extract — Maclura pomifera

Indications (Ethylene/Acetone Extract): Neuropathic pain, trigeminalgia, intercostal neuralgia, psoriasis, seborrheic dermatitis, lichenoid skin lesions, basal cell skin cancer (in complex therapy), dermatosclerosis, chronic neurodermatitis, subcutaneous tissue fibrosis.

Standard Dosage (Ethylene/Acetone Extract): Locally, 2 times a day, apply 1–2 drops to the affected skin area. Course — 14 days.

Enhanced Dosage (Ethylene/Acetone Extract): 3 times a day, 3 drops per focus of inflammation for active psoriasis, fibrous plaques, and areas of chronic neuropathy with a pronounced pain component. Duration — up to 10 days, then a reduction in frequency.

Maximum Dosage (Ethylene/Acetone Extract): Up to 4 applications per day, 4–5 drops. Recommended for dermatological pathologies with pronounced hyperplasia and skin fibrosis. Maximum duration — no more than 7 days consecutively.

Preventive Dosage (Ethylene/Acetone Extract): Once a day, pointwise, 1 drop on the skin in the remission zone for previously diagnosed dermatoses or a tendency to nodular inflammations. Course — 10 days, repeat 2–3 times a year.

Pediatric Dosage (Ethylene/Acetone Extract): Not recommended for children under 16 years of age. In adolescents 16–18 years of age, use of 1 drop once a day is possible, no more than 7 days. Under medical supervision, only for localized forms of neurodermatitis.

Contraindications (Ethylene/Acetone Extract): Pregnancy, lactation, age under 16 years, active pustular skin diseases, contact allergy to organic solvents. Data on safety during pregnancy and lactation have not been registered, so use is contraindicated.

Side Effects (Ethylene/Acetone Extract): Local reactions have been registered: burning, hyperemia, peeling, increased inflammatory response when the dose is exceeded. In isolated cases — contact dermatitis.

Adjustment for Patient Body Weight: With weight less than 60 kg — a reduction in the number of drops by 25%. With body weight above 90 kg, an application area up to 2 times larger than the standard is possible.

Preparation Method (Ethylene/Acetone Extract): To prepare 100 ml of extract, take 100 grams of fresh maclura fruits ground into fine shavings. Add 100 ml of a mixture of acetone (70%) and ethyl acetate (30%) as a solvent. Infuse in an airtight glass container at a temperature of 22–25 degrees Celsius for 5 days. Then filter through an ashless filter, evaporate to half the volume at 35 degrees Celsius, and bring to 100 ml with purified olive emulsion. Store in a light-proof container.

Storage Conditions and Shelf Life (Ethylene/Acetone Extract): Store in a hermetically sealed dark glass container, at a temperature from 4 to 10 degrees Celsius, in a place protected from light and EMI. Shelf life — 6 months. After opening, use within 20 days.

Cream/Ointment/Serum — Maclura pomifera

Indications (Cream/Ointment/Serum): Age-related skin changes, photoaging, decreased elasticity, hyperpigmentation, couperose, psoriasis, neurodermatitis, lichenoid dermatoses, chronic skin dryness, skin fibrosis, recovery after laser procedures and chemical peels.

Standard Dosage (Cream/Ointment/Serum): Once a day in the evening, apply a thin layer to clean skin of the face or body, for 21 days. Repeat course — after a 7-day break.

Enhanced Dosage (Cream/Ointment/Serum): 2 times a day (morning and evening), in a course of up to 14 days. Used for pronounced hyperpigmentation, age-related skin atrophy, chronoaging, as well as for remodeling postoperative scars.

Maximum Dosage (Cream/Ointment/Serum): Up to 3 applications per day on limited areas (no more than 10×10 cm), no more than 7 days consecutively. Used for severe forms of psoriasis, skin fibroses, as part of complex programs for correcting age-related skin changes.

Preventive Dosage (Cream/Ointment/Serum): Once a day, in the evening, in 10-day courses once a season. Suitable for patients over 40 years of age, with dry skin, photodamage, decreased turgor, as a component of anti-age care.

Pediatric Dosage (Cream/Ointment/Serum): Not recommended for children under 12 years of age. From 12 years of age — local application no more than once a day, on limited areas for seborrheic and dry dermatitis. Only as prescribed by a specialist.

Contraindications (Cream/Ointment/Serum): Individual sensitivity to components, active form of rosacea, open wounds, pregnancy (in the first trimester), age under 12 years. There are no scientific data on systemic teratogenic action; however, safety in the first trimester has not been established.

Side Effects (Cream/Ointment/Serum): Contact dermatitis, feeling of tightness, erythema, skin peeling. In rare cases — an allergic reaction in the form of urticaria with sensitive skin.

Adjustment for Patient Body Weight: Not required. Only the application area and frequency are regulated. With body weight up to 50 kg — use no more than once a day. With body weight above 90 kg, an expansion of the application area is permissible.

Preparation Method (Cream/Ointment/Serum): To obtain 100 grams of cream: take 2 grams of CO2 extract of maclura, 10 grams of shea butter, 8 grams of grape seed oil, 5 grams of beeswax, 70 grams of distilled water, and 5 grams of natural emulsifier (for example, olive 1000). Heat the oil phase (extract, oils, wax) in a water bath to 65 degrees Celsius. Heat the water phase separately to the same temperature. Gradually combine the water phase with the oil phase with intensive stirring. After cooling to 40 degrees, add the CO2 extract. Whip the finished mass to a creamy consistency and package into glass containers.

Storage Conditions and Shelf Life (Cream/Ointment/Serum): Store in a glass airtight container, in a refrigerator at a temperature from 4 to 8 degrees Celsius. Avoid direct light and heating. Shelf life — 45 days. After opening, use within 20 days, avoiding contact with hands (use a spatula).

Anti-Aging Serum — Maclura pomifera

Indications (Anti-Aging Serum): Chronoaging of the skin, photodamage, decreased synthesis of collagen types I and III, loss of skin elasticity, dull complexion, dryness, wrinkles, sagging skin of the eyelids, periorbital edema, couperose, post-peel recovery.

Standard Dosage (Anti-Aging Serum): Once a day in the evening, 3–4 drops on the face and neck, on cleansed moist skin. With light patting movements until completely absorbed. Course — 21 days.

Enhanced Dosage (Anti-Aging Serum): 2 times a day (morning and evening), 4–5 drops, in combination with cream or without. Prescribed for pronounced signs of dermatosastoidosis, deformation type of aging, decreased skin density. Course — 14 days, then transition to the standard dose.

Maximum Dosage (Anti-Aging Serum): Up to 3 applications per day, pointwise, no more than 6 drops at a time. Permitted short-term (no more than 7 days consecutively) for pronounced skin atony, deep wrinkle network, and reconstructive therapy after peels and lasers.

Preventive Dosage (Anti-Aging Serum): Once a day every other day, 2–3 drops in the evening, for 14 days. Suitable for patients 35+, with the first signs of age-related changes, a tendency to photoaging, and deterioration of skin turgor. Preventive course — 2 times a year.

Pediatric Dosage (Anti-Aging Serum): Not used in children and adolescents under 18 years of age. Safety and efficacy for pediatric use have not been established.

Contraindications (Anti-Aging Serum): Individual hypersensitivity, active form of acne, pregnancy and lactation, age under 18 years. The safety of use during pregnancy and breastfeeding has not been clinically confirmed.

Side Effects (Anti-Aging Serum): Redness, tingling, peeling, in isolated cases — an allergic reaction to components, may be observed. With overdose — a feeling of tightness, dryness, irritation.

Adjustment for Patient Body Weight: Not required. The dosage is determined locally, depending on the application area. With weight less than 50 kg, it is recommended to start with a minimal volume (2 drops), especially with sensitive skin.

Preparation Method (Anti-Aging Serum): To prepare 100 ml of anti-aging serum, take: 1.5 grams of CO2 extract of maclura, 5 grams of kelp extract, 3 grams of sea buckthorn oil, 0.8 grams of sodium hyaluronate (0.8%), 2 grams of Centella asiatica extract, 88 ml of Damask rose hydrolate. Combine all water-soluble components, then gradually add fat-soluble ones with constant stirring until a homogeneous emulsion. Cool to a temperature of 25 degrees Celsius, pour into dark glass dropper bottles.

Storage Conditions and Shelf Life (Anti-Aging Serum): Store at a temperature from 4 to 8 degrees Celsius in a refrigerator, in a hermetically closed glass package protected from light and sources of electromagnetic radiation. Shelf life — 45 days. After opening, use within 20 days. Avoid contact with hand skin — use only through a dispenser or pipette.

Toxicity and Biosafety of Maclura pomifera

Based on toxicological studies using extracts of Maclura pomifera fruits, it was established that subchronic administration of alcohol and chloroform extract at doses up to 2000 mg/kg of body weight did not cause lethal outcomes in laboratory animals (rats, mice), which indicates low acute toxicity. Thus, the LD50 value (lethal dose for 50% of the population) for the alcohol extract of maclura in mice is estimated as >2000 mg/kg with oral administration.

The absence of pronounced hematological and histopathological changes with prolonged use of doses up to 500 mg/kg for 28 days has also been noted. The product is considered conditionally safe for topical and oral use in traditionally used concentrations. However, with parenteral administration and the use of concentrated organic extracts, irritation and contact toxicity are possible.

Studies on pregnant and lactating animals have not been conducted. The teratogenic, embryotoxic, and carcinogenic potential of osage orange has not been fully assessed, which requires caution when used in vulnerable groups.

Reference: https://www.sciencedirect.com/...

Pharmacodynamics — Maclura pomifera

The pharmacodynamic activity of Maclura pomifera is determined by a wide range of biologically active compounds, among which flavonoid derivatives, in particular osajin and pomiferin, as well as triterpenes, phytosterins, and fatty acid fractions, are of key importance. These components together determine the multisystem pharmacodynamic effect on the human body.

Isoflavonoids with pronounced antioxidant potential have been identified in the composition of Maclura pomifera fruits. The mechanism of their action is associated with the neutralization of reactive oxygen species (ROS) and inhibition of lipid peroxidation, which leads to the stabilization of cell membranes of various tissues. This provides systemic protection against oxidative stress, especially at the level of the skin, vascular endothelium, and nervous tissue.

Flavonoid compounds have an effect on the enzymatic activity of cyclooxygenase-2 (COX-2) and 5-lipoxygenase, which determines the anti-inflammatory effect of the plant. Pomiferin, one of the main biomarkers of the raw material, is able to modulate the synthesis of pro-inflammatory mediators, including prostaglandins and leukotrienes, without affecting the basal level of COX-1. Such selectivity potentially reduces the risk of side effects associated with gastrointestinal toxicity.

A moderate inhibitory effect on tyrosinase and metalloproteinase activity has also been described, which may indicate a potential dermatotropic activity of maclura. These properties are realized at the local level when extracts are applied to the skin, where an improvement in microcirculation, a decrease in transepidermal water loss, and normalization of keratinization are observed. In addition, under in vitro conditions, it has been proven that the components of Maclura pomifera reduce the expression of enzymes involved in collagen degradation, which is associated with maintaining the integrity of the intercellular matrix.

The target system is the immune system. According to publications, isoflavone derivatives of Maclura pomifera are able to reduce the level of pro-inflammatory cytokines (including TNF-α, IL-6), while increasing the expression of IL-10, which has immunoregulatory properties. Against this background, a restoration of the Th1/Th2 balance and activation of nonspecific cellular immunity (macrophages, NK cells) are observed. These effects indicate the immunomodulatory nature of the plant extract's action.

The neurotropic potential of maclura extracts has also been confirmed experimentally. Pomiferin demonstrated the ability to bind to gamma-aminobutyric acid (GABA) in receptor models, which may be associated with its moderate sedative effect with systemic administration. An antinociceptive effect is also observed, presumably mediated through a decrease in the production of substance P and prostaglandins in peripheral tissues.

The target system is the endocrine system. Phytosteroids found in the oil fraction can modulate the activity of estrogen-type receptors, which gives reason to consider Maclura pomifera as a source of plant phytoestrogens. These compounds are able to weakly activate nuclear receptors involved in the regulation of cell proliferation of epithelial and connective tissue structures.

In addition to the above, triterpene compounds and fatty acids contained in CO2 extracts have a membrane-stabilizing, anti-edematous, and angioprotective effect. This is due to their ability to reduce the permeability of the vascular wall and normalize the tone of smooth muscle cells of small vessels.

Thus, Maclura pomifera is characterized by a polyvalent pharmacodynamic action with a predominant effect on the immune, skin, nervous, and endocrine systems. The mechanisms of action are realized both at the local and systemic levels, involving enzymatic cascades, cellular regulation signaling pathways, and receptor interactions.

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

Pharmacokinetics — Maclura pomifera

The pharmacokinetics of the active compounds of Maclura pomifera in direct human models has been studied fragmentarily. However, according to data obtained from animal and in vitro studies, as well as based on generalized characteristics of flavonoid and terpene compounds, it is possible to present a general kinetic model of assimilation and excretion of the components of this plant.

With oral administration in the form of powder, tincture, or dry extract, the active substances undergo primary absorption in the small intestine. The main compounds — flavonoids, phytosterins, and triterpenes — are absorbed mainly in the form of aglycones or with the participation of intestinal microflora capable of cleaving complex glycosidic bonds. The key link in biotransformation at this stage is bacterial deglycosylation, after which the resulting compounds are absorbed by passive diffusion.

The peak concentration of active substances in blood plasma is reached relatively slowly compared to simple hydrophilic components due to the lipophilic nature of most bioactive metabolites. This determines the predominant distribution in highly vascularized tissues with increased lipid concentration — skin, liver, adipose tissue, adrenal glands, and nervous system. Studies on an ex vivo skin model indicate the transdermal penetrating ability of Maclura pomifera extracts, especially in the form of CO2 extracts and oil infusions. Their accumulation in the epidermis and papillary dermis has been proven, with slow release within 6–12 hours after application.

Metabolism occurs mainly in the liver. Hepatocytes participate in phase I metabolism, carrying out hydroxylation and demethylation of flavonoid structures with the participation of cytochrome P450 isoenzymes. This is followed by phase II — glucuronidation, sulfation, and methylation, which increase the water solubility of metabolites for subsequent excretion. Some components (especially lipophilic triterpenes) may show a tendency to cumulation with prolonged intake in high doses.

Transdermal and topical application is accompanied by minimal systemic absorption; however, local accumulation of active compounds in the skin is possible, especially with a long course. Excretion is carried out mainly through bile and intestines, to a lesser extent — by the kidneys with urine. The participation of skin and sebaceous glands in the excretion of fat-soluble components with topical application has been established. The excretion period varies depending on the form and frequency of use, but remains within the limits characteristic of slowly metabolized flavonoids and terpenes.

Of particular importance is the interaction of the active compounds of Maclura pomifera with intestinal microflora with oral administration. Some components are subject to biotransformation only in the presence of specific bacteria that ensure their enzymatic activation. This indicates the importance of individual differences in the microbiome in the efficacy and kinetics of the action of maclura-based preparations.

Thus, the pharmacokinetics of Maclura pomifera components combines elements of local action (with topical and transdermal application) and systemic action through intestinal absorption and hepatobiliary metabolism. The excretion mechanisms are adapted to the predominantly lipophilic nature of the molecules and their tendency to tissue binding.

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

Mechanisms of Action and Scientific Rationale — Maclura pomifera

The main mechanisms of action of Maclura pomifera components are determined by the presence of biologically active flavonoids, isoflavonoids, and triterpenes, which have a modulating effect on enzyme systems, cellular receptors, and signaling pathways. One of the most studied components is pomiferin — an isoflavonoid demonstrating inhibitory activity against COX-2 (cyclooxygenase-2) and 5-LOX (5-lipoxygenase) enzymes, which leads to a decrease in the synthesis of pro-inflammatory mediators, including prostaglandins and leukotrienes. This suppresses the activation of inflammatory cascades involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), which, in turn, limits the expression of IL-1β, TNF-α, and IL-6 cytokines.

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

The flavonoid and polyphenolic structures of Maclura pomifera have an antioxidant effect through the neutralization of reactive oxygen species (ROS) and the restoration of redox homeostasis. It has been established that these compounds increase the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in tissues subjected to oxidative damage. The antioxidant effect is due not only to the direct capture of free radicals but also to the modulation of transcription factors, including Nrf2 (nuclear factor erythroid 2–related factor 2), responsible for activating the antioxidant response at the cellular level.

References: https://www.ncbi.nlm.nih.gov/p...; https://link.springer.com/arti...

Isoflavonoids and phytosterins isolated from maclura extracts have demonstrated the ability to influence the activity of estrogen-type receptors (ERα and ERβ), as well as suppress aromatase expression. These interactions indicate potential participation in the regulation of hormone-dependent processes, which is confirmed by cell proliferation and apoptosis models. An effect on the expression of proteins of the Bcl-2 family and caspases has also been found, which suggests an antiproliferative and apoptosis-inducing mechanism of action at high concentrations of phytoextracts.

References: https://pubmed.ncbi.nlm.nih.go...; https://www.researchgate.net/p...

Triterpenes and fatty acids that affect cell membranes and vascular tone have been identified in the composition of CO2 and oil extracts of maclura. The mechanisms of action of these lipophilic components are associated with the activation of PPARγ receptors (peroxisome proliferator-activated receptor gamma) involved in the regulation of lipid metabolism, inflammation, and cell differentiation. In addition, their participation in suppressing the expression of MMPs (matrix metalloproteinases), in particular MMP-2 and MMP-9, has been established, which can limit the degradation of the extracellular matrix and provide dermatotropic and vasoprotective effects.

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

Some compounds found in the composition of extracts have demonstrated the ability to modulate the activity of GABA receptors (γ-aminobutyric acid), which indicates a moderate neurosedative effect. This is mediated through interaction with ionophore structures of receptors and a decrease in the excitability of neuronal networks. Such effects are characteristic of flavonoids with affinity for the benzodiazepine site of GABA receptors. In parallel, a decrease in the concentration of substance P in peripheral tissues and normalization of the sensitivity of afferent fibers are observed.

References: https://www.ncbi.nlm.nih.gov/p...; https://www.tandfonline.com/do...

In total, the pharmacological components of Maclura pomifera demonstrate a modulating effect on a wide range of biotargets, including inflammatory enzyme cascades, receptor complexes, cellular adaptation signaling pathways, apoptosis processes, and restoration of cellular structures. This substantiates the prospects for using plant extracts in multisystem approaches to maintaining physiological homeostasis.

Synergy — Maclura pomifera

The pharmacological synergy of Maclura pomifera with other biologically active substances and phyto-components has been confirmed by a number of studies indicating the potentiation of antioxidant, anti-inflammatory, and immunomodulatory effects with combined use. One of the established directions of synergy is the enhancement of antioxidant protection with the combined use of flavonoid extracts of maclura with green tea polyphenols (Camellia sinensis) and curcuminoids (Curcuma longa). In vitro studies demonstrate that maclura flavonoids (in particular, pomiferin) enhance the activity of antioxidant enzymes in cell culture when added in combination with epigallocatechin gallate, which indicates an additive and partially potentiating interaction.

References: https://www.sciencedirect.com/science/article/abs/pii/S2221169115300106; https://pubmed.ncbi.nlm.nih.gov/32512560/

Additional data have been obtained on synergy with saponins of Panax ginseng and flavonoid complexes from Ginkgo biloba. The combined use of Maclura pomifera extracts with ginsenosides showed a potentiating effect on reducing the level of pro-inflammatory cytokines (IL-6, TNF-α) in a model of LPS-induced inflammatory response. This interaction is realized, probably, through the suppression of the common NF-κB signaling pathway and stabilization of mitochondrial membrane potential. In turn, the addition of ginkgo extracts improved the microcirculatory response and enhanced the antiplatelet properties of the complex, which may be due to the complementary effect on platelet factors and endothelium.

References: https://www.ncbi.nlm.nih.gov/p...; https://link.springer.com/arti...

Synergism with triterpenes of Centella asiatica demonstrated a tissue-specific character: in vitro models of skin fibroblasts showed higher expression of type I collagen with the combined action of asiaticoside and maclura flavonoids compared to mono-exposure of each component. This confirms the presence of a positive interaction at the level of extracellular matrix remodeling, probably through joint modulation of the TGF-β signaling cascade and inhibition of metalloproteinase activity.

References: https://www.sciencedirect.com/...; https://www.researchgate.net/p...

Separate publications indicate the modulating nature of the interaction of Maclura pomifera with ω-3 fatty acids. In a skin explant model, synergism was observed in reducing the expression of pro-inflammatory prostaglandins and LOX-dependent metabolites with combined use with docosahexaenoic acid. This may indicate a protective interaction aimed at stabilizing membrane phospholipids and reducing lipid peroxidation.

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

In general, Maclura pomifera demonstrates predominantly additive and potentiating synergism with plant compounds that have a similar direction of action: antioxidant, anti-inflammatory, dermatotropic, and immunomodulatory. Such combinations enhance biological activity and allow affecting multiple cellular and signaling targets, including COX-2, LOX, NF-κB, TGF-β, PPARγ, and cytokine receptors. Synergy is realized both at the cellular, tissue, and systemic levels, providing an expansion of the spectrum of pharmacological effects.

Geography of Use and Traditional Medicine — Maclura pomifera

Maclura pomifera, known as osage orange, is traditionally distributed in the central and southern regions of North America, especially in the territories of the modern states of Oklahoma, Texas, Kansas, Missouri, and Arkansas, as well as in Mexico. Its historical use dates back to the practice of the indigenous peoples of North America, including the Osage, Cherokee, and Comanche tribes, from whom one of the common English names of the plant — "osage orange" — probably originates. In Osage culture, maclura wood was used to make bows, as it was considered extremely strong and flexible, and the wood itself was revered as a "sacred tree of war." In the ritual practice of the tribes, bows made of maclura were often passed down by inheritance as objects of power and a symbol of military honor.

The fruits of Maclura pomifera were not consumed as food in the traditional practice of Native Americans, but their milky sap and infusions were used topically. In the ethnomedical rituals of the Cherokee and other tribes, milky sap was used as a base for ointments intended for lubricating joints and body areas affected by various external manifestations. In these traditions, the plant was considered "fiery," capable of expelling intra-body and extra-cutaneous "spirits of disease" through heating and irritation caused by resinous substances. In some rituals, milky sap was mixed with ash and applied in the form of signs on the skin during a purification rite.

With the expansion of European colonization, the plant was introduced into culture as an ornamental and protective plant, actively planted in hedges. Already in the 19th century, it entered the composition of American apothecary practices, where alcohol tinctures and extracts from fruits and wood began to be used in home recipes. In the tradition of American herbalism of the early 20th century, there are mentions of the use of external compresses based on alcohol tincture for rubs, as well as descriptions of adding crushed raw materials to oil bases for rubbing. In Anglo-American folklore, the tree was also endowed with the function of protecting the home: fruits were laid out in the corners of the house or in attics as a remedy against insects and "unclean spirits."

In Mexico, in some regions of folk medicine, the leaves and fruits of the plant were used as part of warm poultices and wraps. In Central American practice, the use of a decoction of the bark for rubs and as part of baths has been noted, which was associated with ideas about removing "internal heat" and restoring the energy balance of the body.

Non-medical use of Maclura pomifera included ritual fumigations, the manufacture of amulets and protective objects, as well as the use of wood for the production of tools and weapons. The image of the plant is preserved in the folklore and craft practices of the indigenous and settler cultures of North America up to the present time.