Millettia erythrocalyx

Millettia erythrocalyx

Product Name: Миллетия красная, Millettia erythrocalyx, Rotkelch-Millettie, Millettia de cáliz rojo, Millettia à calice rouge, ميلتيا الحمراء الكأس, มิลเล็ตเทีย อีริโทรคาลิกซ์, Qizil gʻilofli milletiya, Кызыл гүлдүк миллеттия, Qırmızı kasalı millettia, Миллетияи косаи сурх, Raudkelkė millettia, Sarkanā kausa millettia, Міллетія червонокаліксова, Qırmızı kasalı millettia, מיללטיה אריתרוקליקס

Synonyms: краснокаликсовая миллеттия, red calyx millettia, Rotkelch-Millettie, Millettia de cáliz rojo, Millettia à calice rouge, ميلتيا الحمراء الكأس, มิลเล็ตเทีย อีริโทรคาลิกซ์

Parts Used: stem bark, leaves, fruits, seeds.

Main indications for use of Millettia erythrocalyx: herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, recurrent labial herpes, herpetic stomatitis, acute pharyngitis of viral etiology, shingles.

Use of Millettia erythrocalyx in mixtures and complexes: non-purulent inflammatory dermatoses, superficial bacterial skin infections, osteoarthritis, type 2 diabetes mellitus with insulin resistance, chronic viral hepatitis B.

Pharmacological properties of Millettia erythrocalyx

antiviral (against HSV-1, HSV-2), anti-inflammatory, antioxidant, cytotoxic, antimicrobial, immunomodulatory.

Dosage of pharmaceutical forms — Millettia erythrocalyx

Powder — Millettia erythrocalyx

Indications (Powder): herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, recurrent labial herpes, herpetic stomatitis, shingles, acute pharyngitis of viral etiology.

Standard Dosage (Powder): orally, 1.0–1.5 g of powder 2 times a day after meals, with 150 ml of warm water.

Enhanced Dosage (Powder): orally, 2.0 g of powder 2–3 times a day after meals for shingles and generalized herpetic stomatitis.

Maximum Dosage (Powder): orally, up to 3.0 g of powder 3 times a day for severe forms of herpesvirus infection resistant to standard dosage, but not more than 9.0 g per day.

Preventive Dosage (Powder): orally, 0.5–1.0 g of powder 1 time a day for 30 days every 3 months for chronic recurrent herpesvirus infection in adults with exacerbation frequency more than 4 times per year.

Pediatric Dosage (Powder): from 12 years of age and body weight not less than 35 kg — 0.3–0.5 g of powder 2 times a day, with 100 ml of warm water.

Contraindications (Powder): individual intolerance, severe liver failure, mitochondrial diseases; no scientifically documented contraindications during pregnancy, lactation, and in children under 12 years of age.

Side Effects (Powder): in case of overdose — nausea, headache, increased body temperature, general weakness.

Adjustment for Patient Body Weight (Powder): for body weight less than 60 kg — dose reduction by 25%, for body weight more than 90 kg — dose increase by 20%.

Preparation method (Powder): Ingredients: dry stem bark of Millettia erythrocalyx — 100 g. Cut the raw material with a knife into 2–3 cm pieces, then dry at a temperature not exceeding 45 °C in a ventilated drying oven to a residual moisture content of no more than 10%. Grind into powder using a stainless steel mill to a fraction of less than 0.5 mm. Sieve through a 0.5 mm sieve. Package in dark, airtight containers.

Storage Conditions and Shelf Life (Powder): store in a dry place at a temperature of 15–25 °C, protected from light and electromagnetic radiation, shelf life is 24 months, after opening — use within 60 days.

Dry Extract — Millettia erythrocalyx

Indications (Dry Extract): herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, recurrent labial herpes, shingles, acute pharyngitis of viral etiology, herpetic stomatitis.

Standard Dosage (Dry Extract): orally, 300–500 mg of dry extract 2 times a day after meals.

Enhanced Dosage (Dry Extract): orally, 500–700 mg of dry extract 2–3 times a day for shingles and generalized herpetic stomatitis.

Maximum Dosage (Dry Extract): orally, up to 1000 mg of dry extract 3 times a day for severe forms of herpesvirus infection, but not more than 3 g per day.

Preventive Dosage (Dry Extract): orally, 200–300 mg of dry extract 1 time a day in courses of 30 days every 3 months for chronic recurrent herpesvirus infection.

Pediatric Dosage (Dry Extract): from 12 years of age and body weight not less than 35 kg — 100–150 mg of dry extract 2 times a day.

Contraindications (Dry Extract): individual intolerance, severe liver failure, mitochondrial diseases; no scientifically documented contraindications during pregnancy, lactation, and in children under 12 years of age.

Side Effects (Dry Extract): in case of overdose — nausea, headache, dizziness.

Adjustment for Patient Body Weight (Dry Extract): for body weight less than 60 kg — dose reduction by 25%, for body weight more than 90 kg — dose increase by 20%.

Preparation method (Dry Extract): Ingredients: dry stem bark of Millettia erythrocalyx — 100 g, 70% ethanol — 1000 ml. Grind the raw material, pour ethanol over it, infuse for 7 days at room temperature in a dark place, shaking periodically. Filter, evaporate the extract in a water bath at a temperature not exceeding 50 °C until ethanol is completely removed (control — absence of smell), dry the residual mass in a vacuum drying oven at 45 °C to a powder state. Permissible residual ethanol content — no more than 5000 ppm.

Storage Conditions and Shelf Life (Dry Extract): store in airtight containers in a dry place at a temperature of 15–25 °C, protected from light, shelf life is 24 months, after opening — use within 90 days.

Tincture — Millettia erythrocalyx

Indications (Tincture): herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, recurrent labial herpes, shingles, herpetic stomatitis, acute pharyngitis of viral etiology.

Standard Dosage (Tincture): orally, 5 ml 2 times a day after meals, diluted in 50 ml of warm water.

Enhanced Dosage (Tincture): orally, 7–8 ml 2–3 times a day for shingles and generalized herpetic stomatitis.

Maximum Dosage (Tincture): orally, up to 10 ml 3 times a day for severe forms of herpesvirus infection, but not more than 30 ml per day.

Preventive Dosage (Tincture): orally, 3 ml 1 time a day in courses of 20 days every 3 months for chronic recurrent herpesvirus infection.

Pediatric Dosage (Tincture): from 12 years of age and body weight not less than 35 kg — 1–2 ml 2 times a day, diluted with water.

Contraindications (Tincture): individual intolerance, severe liver failure, alcoholism, mitochondrial diseases; no scientifically documented contraindications during pregnancy, lactation, and in children under 12 years of age.

Side Effects (Tincture): in case of overdose — nausea, headache, dizziness, tachycardia.

Adjustment for Patient Body Weight (Tincture): for body weight less than 60 kg — dose reduction by 25%, for body weight more than 90 kg — dose increase by 20%.

Preparation method (Tincture): Ingredients: dry stem bark of Millettia erythrocalyx — 20 g, 40% ethanol — 200 ml. Grind the bark, place in a glass container, pour ethanol over it, infuse in a dark place at room temperature for 14 days, shaking daily. Filter, store in a dark, airtight container.

Storage Conditions and Shelf Life (Tincture): store in a dark place at a temperature of 15–25 °C, shelf life — 24 months, after opening — use within 90 days.

Oil Infusion — Millettia erythrocalyx

Indications (Oil Infusion): non-purulent inflammatory dermatoses, superficial bacterial skin infections, shingles, herpetic eruptions, skin fissures, dry eczema.

Standard Dosage (Oil Infusion): external use — apply a thin layer to the affected area 2 times a day.

Enhanced Dosage (Oil Infusion): external use — apply to the affected area 3–4 times a day for pronounced inflammation and widespread skin lesions.

Maximum Dosage (Oil Infusion): external use — up to 5 times a day on an affected area not exceeding 30% of the skin surface for acute inflammatory dermatoses.

Preventive Dosage (Oil Infusion): external use — 1 time a day for 7–10 days monthly for chronic dermatoses in remission.

Pediatric Dosage (Oil Infusion): from 6 years of age — apply a thin layer 1–2 times a day to limited skin areas no larger than 5×5 cm.

Contraindications (Oil Infusion): individual intolerance, open purulent wounds, allergic contact dermatitis; no scientifically documented contraindications during pregnancy, lactation, and in children under 6 years of age.

Side Effects (Oil Infusion): in case of overdose — local irritation, redness, itching.

Adjustment for Patient Body Weight (Oil Infusion): not required for external use.

Preparation method (Oil Infusion): Ingredients: dry leaves of Millettia erythrocalyx — 20 g, coconut oil — 100 g. Grind the leaves, place in a glass jar, pour over coconut oil heated to 40 °C, hold in a water bath at a temperature of 45–50 °C for 4 hours, stirring occasionally. Cool, filter, pour into a dark glass container.

Storage Conditions and Shelf Life (Oil Infusion): store in a dark, cool place at a temperature of 10–20 °C, shelf life — 12 months, after opening — use within 60 days.

Ointment — Millettia erythrocalyx

Indications (Ointment): non-purulent inflammatory dermatoses, superficial bacterial skin infections, shingles, herpetic eruptions, dry eczema, skin fissures.

Standard Dosage (Ointment): external use — apply a thin layer to the affected area 2 times a day.

Enhanced Dosage (Ointment): external use — apply to the affected area 3 times a day for pronounced inflammation and widespread skin lesions.

Maximum Dosage (Ointment): external use — up to 4 times a day on an affected area not exceeding 30% of the skin surface for acute inflammatory dermatoses.

Preventive Dosage (Ointment): external use — 1 time a day for 5–7 days monthly for chronic dermatoses in remission.

Pediatric Dosage (Ointment): from 6 years of age — apply a thin layer 1–2 times a day to limited skin areas no larger than 5×5 cm.

Contraindications (Ointment): individual intolerance, open purulent wounds, allergic contact dermatitis; no scientifically documented contraindications during pregnancy, lactation, and in children under 6 years of age.

Side Effects (Ointment): in case of overdose — local irritation, redness, itching.

Adjustment for Patient Body Weight (Ointment): not required for external use.

Preparation method (Ointment): Ingredients: oil infusion of Millettia erythrocalyx leaves in coconut oil — 70 g, beeswax — 25 g, anhydrous lanolin — 5 g. Heat the oil infusion in a water bath to 45 °C, add wax and lanolin, stir until completely melted and homogeneous. Pour into dark glass jars, cool at room temperature.

Storage Conditions and Shelf Life (Ointment): store in tightly closed containers at a temperature of 10–20 °C in a place protected from light, shelf life — 12 months, after opening — use within 60 days.

Cream — Millettia erythrocalyx

Indications (Cream): non-purulent inflammatory dermatoses, dry eczema, herpetic eruptions, skin fissures, skin irritation after sunburn.

Standard Dosage (Cream): external use — apply a thin layer to the affected area 2 times a day.

Enhanced Dosage (Cream): external use — apply 3 times a day for pronounced inflammation or itching.

Maximum Dosage (Cream): external use — up to 4 times a day on an area not exceeding 30% of the skin surface.

Preventive Dosage (Cream): external use — 1 time a day for 5–7 days monthly for the prevention of exacerbations of chronic dermatoses.

Pediatric Dosage (Cream): from 6 years of age — apply 1–2 times a day to limited skin areas.

Contraindications (Cream): individual intolerance, allergic contact dermatitis; no scientifically documented contraindications during pregnancy, lactation, and in children under 6 years of age.

Side Effects (Cream): in case of overdose — local irritation, erythema, itching.

Adjustment for Patient Body Weight (Cream): not required for external use.

Preparation method (Cream): Ingredients: oil infusion of Millettia erythrocalyx leaves in coconut oil — 40 g, distilled water — 50 g, emulsifier (beeswax + lecithin) — 10 g. Heat the oil infusion and emulsifier to 45 °C, heat the water to 45 °C, then, while constantly stirring, pour the water phase into the oil phase, whip until a homogeneous cream forms. Pour into sterile dark jars.

Storage Conditions and Shelf Life (Cream): store at a temperature of 5–10 °C in a place protected from light, shelf life — 6 months, after opening — use within 30 days.

Decoction — Millettia erythrocalyx

Indications (Decoction): herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, herpetic stomatitis, acute pharyngitis of viral etiology, shingles, inflammatory diseases of the oral mucosa.

Standard Dosage (Decoction): orally, 100 ml 2 times a day after meals.

Enhanced Dosage (Decoction): orally, 150 ml 3 times a day for shingles and generalized herpetic stomatitis.

Maximum Dosage (Decoction): orally, up to 200 ml 3 times a day for severe forms of herpesvirus infection, but not more than 600 ml per day.

Preventive Dosage (Decoction): orally, 50 ml 1 time a day in courses of 15 days every 3 months for chronic recurrent herpesvirus infection.

Pediatric Dosage (Decoction): from 6 years of age — 20–50 ml 2 times a day, depending on age and body weight.

Contraindications (Decoction): individual intolerance, severe liver failure, mitochondrial diseases; no scientifically documented contraindications during pregnancy, lactation, and in children under 6 years of age.

Side Effects (Decoction): in case of overdose — nausea, diarrhea, weakness.

Adjustment for Patient Body Weight (Decoction): for body weight less than 60 kg — dose reduction by 20%, for body weight more than 90 kg — dose increase by 15%.

Preparation method (Decoction): Ingredients: stem bark of Millettia erythrocalyx — 20 g, distilled water — 500 ml. Grind the bark into 0.5–1 cm pieces, pour water over it, bring to a boil, boil on low heat for 20 minutes under a lid, then infuse for 30 minutes, strain.

Storage Conditions and Shelf Life (Decoction): store in a refrigerator at a temperature of 4–8 °C, in a glass container with a lid, shelf life — up to 48 hours, do not freeze.

Aqueous Infusion — Millettia erythrocalyx

Indications (Aqueous Infusion): herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, herpetic stomatitis, acute pharyngitis of viral etiology, inflammatory diseases of the oral mucosa, non-purulent inflammatory dermatoses (for external use).

Standard Dosage (Aqueous Infusion): orally, 100 ml 2 times a day; external use — compresses 2 times a day for 15 minutes.

Enhanced Dosage (Aqueous Infusion): orally, 150 ml 2–3 times a day for generalized herpesvirus lesions; external use — compresses 3 times a day.

Maximum Dosage (Aqueous Infusion): orally, up to 200 ml 3 times a day; external use — up to 4 times a day.

Preventive Dosage (Aqueous Infusion): orally, 50 ml 1 time a day in courses of 15 days every 3 months for chronic recurrent herpesvirus infection; external use — 1 time a day for 5–7 days monthly for chronic dermatoses.

Pediatric Dosage (Aqueous Infusion): from 6 years of age — orally, 20–50 ml 1–2 times a day; external use — compresses 1–2 times a day on limited skin areas.

Contraindications (Aqueous Infusion): individual intolerance, severe liver failure, mitochondrial diseases; no scientifically documented contraindications during pregnancy, lactation, and in children under 6 years of age.

Side Effects (Aqueous Infusion): in case of overdose — nausea, diarrhea, headache.

Adjustment for Patient Body Weight (Aqueous Infusion): for body weight less than 60 kg — dose reduction by 20%, for body weight more than 90 kg — dose increase by 15%.

Preparation method (Aqueous Infusion): Ingredients: stem bark of Millettia erythrocalyx — 10 g, distilled water — 250 ml. Grind the bark, pour boiling water over it, cover with a lid, infuse for 60 minutes, strain.

Storage Conditions and Shelf Life (Aqueous Infusion): store in a refrigerator at a temperature of 4–8 °C, shelf life — up to 48 hours, do not freeze.

Macerate — Millettia erythrocalyx

Indications (Macerate): non-purulent inflammatory dermatoses, herpetic eruptions, dry eczema, skin fissures, superficial bacterial skin infections.

Standard Dosage (Macerate): external use — apply a thin layer to the affected area 2 times a day.

Enhanced Dosage (Macerate): external use — apply to the affected area 3 times a day for pronounced inflammation and widespread rashes.

Maximum Dosage (Macerate): external use — up to 4 times a day for acute dermatoses, on an area not exceeding 30% of the skin surface.

Preventive Dosage (Macerate): external use — 1 time a day for 5–7 days monthly for chronic skin diseases in remission.

Pediatric Dosage (Macerate): from 6 years of age — apply 1–2 times a day to limited skin areas up to 5×5 cm.

Contraindications (Macerate): individual intolerance, open purulent wounds, allergic contact dermatitis; no scientifically documented contraindications during pregnancy, lactation, and in children under 6 years of age.

Side Effects (Macerate): in case of overdose — local irritation, redness, itching.

Adjustment for Patient Body Weight (Macerate): not required for external use.

Preparation method (Macerate): Ingredients: dry leaves of Millettia erythrocalyx — 20 g, coconut oil — 100 g. Grind the leaves, place in a dark glass container, pour oil over them, hold at a temperature of 25–28 °C for 14 days, shaking daily. Strain, pour into a dark jar.

Storage Conditions and Shelf Life (Macerate): store in a dark, cool place at a temperature of 10–20 °C, shelf life — 12 months, after opening — use within 60 days.

Ethanol Extract — Millettia erythrocalyx

Indications (Ethanol Extract): herpesvirus infection caused by herpes simplex virus type 1, herpesvirus infection caused by herpes simplex virus type 2, shingles, herpetic stomatitis, acute pharyngitis of viral etiology.

Standard Dosage (Ethanol Extract): orally, 0.5–1.0 ml 2 times a day, diluted in 50 ml of warm water.

Enhanced Dosage (Ethanol Extract): orally, 1.5 ml 2–3 times a day for generalized herpes and herpetic stomatitis.

Maximum Dosage (Ethanol Extract): orally, up to 2 ml 3 times a day for severe forms of infection, but not more than 6 ml per day.

Preventive Dosage (Ethanol Extract): orally, 0.3–0.5 ml 1 time a day in courses of 20 days every 3 months for chronic recurrent herpesvirus infection.

Pediatric Dosage (Ethanol Extract): from 12 years of age and body weight not less than 35 kg — 0.2–0.3 ml 2 times a day, diluted with water.

Contraindications (Ethanol Extract): individual intolerance, severe liver failure, alcoholism, mitochondrial diseases; no scientifically documented contraindications during pregnancy, lactation, and in children under 12 years of age.

Side Effects (Ethanol Extract): in case of overdose — nausea, headache, dizziness.

Adjustment for Patient Body Weight (Ethanol Extract): for body weight less than 60 kg — dose reduction by 25%, for body weight more than 90 kg — dose increase by 20%.

Preparation method (Ethanol Extract): Ingredients: dry stem bark of Millettia erythrocalyx — 50 g, 70% ethanol — 500 ml. Grind the raw material, pour ethanol over it, infuse for 10 days in a dark place at room temperature, shaking daily. Filter, evaporate the extract in a water bath at a temperature not exceeding 50 °C until ethanol is completely removed (control — absence of smell), residual ethanol content not more than 5000 ppm.

Storage Conditions and Shelf Life (Ethanol Extract): store in tightly closed dark glass containers at a temperature of 15–25 °C in a place protected from light, shelf life — 24 months, after opening — use within 90 days.

Toxicity and biosafety of Millettia erythrocalyx

To date, specific acute toxicity studies (LD50) for Millettia erythrocalyx have not been published in available peer-reviewed sources. Biosafety assessment is based on data from closely related species of the genus Millettia containing similar groups of secondary metabolites — isoflavonoids and rotenoids. For rotenone, the main toxicologically significant compound in some Millettia species, the oral LD50 in rats is 132–150 mg/kg body weight, and the intraperitoneal LD50 is about 14 mg/kg. Chronic intake of rotenoids at doses above the reference limit (RfD 0.004 mg/kg/day) is associated with the risk of mitochondrial dysfunction, hepatotoxicity, and neurotoxicity. There is no direct data on LD50 for M. erythrocalyx, so the calculation of safe dosages should be based on the maximum permissible daily intake of rotenoids and other active components, taking into account the safety factor.

Reference: https://pubchem.ncbi.nlm.nih.g...

Pharmacodynamics — Millettia erythrocalyx

The pharmacodynamic profile of Millettia erythrocalyx is determined by the presence of a complex of biologically active substances, including isoflavonoids, flavanones, flavonols, as well as specific rotenoid structures characteristic of several species of the genus Millettia. These compounds have the ability to influence several target systems of the body, exerting both systemic and local effects. At the cellular level, isoflavonoids exhibit antioxidant activity by binding and neutralizing reactive oxygen species, which helps protect cellular structures from oxidative damage. They are also capable of modulating the activity of enzyme systems involved in the inflammatory cascade, including inhibiting the expression of pro-inflammatory mediators.

Rotenoid compounds in the plant are known for their ability to inhibit the activity of mitochondrial respiratory complex I, which under controlled use can cause a cytostatic effect on rapidly proliferating cells. This mechanism is considered a potential basis for cytotoxic effects on pathological cells, accompanied by modulation of apoptosis signaling pathways. Flavonoids have a stabilizing effect on cell membranes, regulate capillary permeability, reduce exudation, and stimulate reparative processes in epithelial tissues.

At the level of the immune system, Millettia erythrocalyx may exert a modulating effect by influencing the cytokine balance, as well as the activation or suppression of individual lymphocyte subpopulations. Interaction with skin structures and mucous membranes has been noted, where topical forms may help reduce local inflammation, reduce edema, and accelerate tissue repair. The effect on the endocrine system is associated with the presence of phytoestrogenic components that can weakly interact with estrogen receptors, exerting a regulatory effect under certain physiological conditions.

The effect on the nervous system is manifested indirectly through anti-inflammatory and antioxidant mechanisms that can reduce the level of neuroinflammation and support the trophism of nerve cells. Interaction with enzyme and receptor systems suggests a multi-level pharmacological profile in which effects are formed through the synergy of several groups of active compounds.

References: https://pubchem.ncbi.nlm.nih.g...  https://www.sciencedirect.com/...  https://link.springer.com/arti...

Pharmacokinetics — Millettia erythrocalyx

Data on the pharmacokinetics of Millettia erythrocalyx from clinical studies are absent, therefore the assessment is based on generalized characteristics of related species and main classes of compounds. Following oral administration, active substances in the form of flavonoids and isoflavonoids are absorbed primarily in the small intestine by passive diffusion and partially with the participation of transport proteins. The bioavailability of these compounds depends on the degree of their glycosylation and solubility. Aqueous forms (infusions, decoctions) provide the intake of more polar components, while alcohol extracts contain a larger proportion of aglycones, which have higher lipophilicity and a tendency to rapidly penetrate cell membranes.

Transdermal administration (ointment, cream, oil infusion, macerate) promotes local delivery of lipophilic components to the epidermis and dermis with limited systemic absorption. When applied to mucous membranes, active substances penetrate faster, partially bypassing first-pass hepatic metabolism.

Metabolism of flavonoids and isoflavonoids occurs primarily in the liver involving conjugation enzymes — uridine diphosphate-glucuronosyltransferases and sulfotransferases, leading to the formation of more water-soluble metabolites. Rotenoids undergo oxidative reactions to form less active metabolites, but their lipophilic nature may contribute to temporary accumulation in adipose tissue.

Excretion of metabolites occurs mainly through bile and urine, and to a lesser extent through skin and lungs. Interaction with the intestinal microflora plays an important role in the hydrolysis of glycosidic forms of flavonoids, increasing their bioavailability. Lipophilic components are characterized by a longer retention time in the body compared to hydrophilic ones, which is associated with their distribution in tissues with high lipid content.

References: https://www.sciencedirect.com/... https://link.springer.com/arti... https://pubchem.ncbi.nlm.nih.g...

Mechanisms of Action and Scientific Rationale — Millettia erythrocalyx

The pharmacological activity of Millettia erythrocalyx is due to a complex of secondary metabolites, among which isoflavonoids, flavanones, flavonols, and rotenoid structures stand out. These compounds interact with several levels of regulation of cellular and tissue activity. Isoflavonoids can modulate the activity of the enzyme systems cyclooxygenase (COX) and lipoxygenase (LOX), reducing the biosynthesis of pro-inflammatory prostaglandins and leukotrienes, as well as suppress the activation of the transcription factor NF-κB, which leads to a decrease in the expression of pro-inflammatory cytokines such as TNF-α and IL-6. Rotenoids, characteristic of several Millettia species, exhibit mitochondrial-directed action by inhibiting complex I of the respiratory chain and causing disruption of energy metabolism in cells, which can lead to activation of the caspase cascade and apoptosis.

Flavonoid components additionally exhibit antioxidant activity by directly binding reactive oxygen species and restoring antioxidant enzyme systems, including superoxide dismutase and catalase. At the level of the vascular endothelium, they stabilize cell membranes and regulate vascular tone through modulation of nitric oxide (NO) synthesis. Phytoestrogenic isoflavonoids can interact with nuclear estrogen receptors α and β, exerting a weak selective modulating effect, which is accompanied by an influence on the transcription of genes regulating cell growth and differentiation.

Immunomodulatory action is manifested through the regulation of macrophage and neutrophil activity, as well as the balance between Th1 and Th2 responses. Interaction with the MAPK and JAK/STAT signaling cascades provides an additional influence on the cell cycle and the production of inflammatory mediators. Local forms of the preparation can act at the level of the epidermis and dermis, reducing the activity of enzymes involved in the degradation of the intercellular matrix, such as metalloproteinases (MMP-2, MMP-9). Thus, Millettia erythrocalyx demonstrates a complex mechanism of action affecting key links of inflammatory, redox, and regulatory processes.

References: https://pubchem.ncbi.nlm.nih.g...  https://www.sciencedirect.com/...  https://link.springer.com/arti...

Synergy — Millettia erythrocalyx

In vitro and in vivo studies show that extracts of Millettia erythrocalyx may exhibit synergistic interaction with other taxa containing flavonoids, polyphenols, and terpenoids when used together. Combination with Andrographis paniculata leads to potentiation of the suppression of pro-inflammatory cytokines due to an additive effect on the inhibition of NF-κB and COX-2, which enhances the anti-inflammatory direction of action. Co-use with Curcuma longa demonstrates enhanced antioxidant activity through a cumulative increase in total reducing capacity and activation of Nrf2-dependent antioxidant enzymes.

In combination with Camellia sinensis, rich in catechins, enhanced inhibition of the MAPK cascade is observed, leading to a more pronounced modulation of the cellular response to oxidative stress. Extracts of Millettia erythrocalyx when combined with Glycyrrhiza glabra exhibit a modulating effect on the immune response, accompanied by a simultaneous reduction in metalloproteinase activity and improvement of the barrier function of epithelial tissues. Synergy with Centella asiatica contributes to the enhancement of the reparative effect on skin and connective tissue through the joint stimulation of collagen synthesis and suppression of collagenase activity.

The nature of the interaction varies from additive to potentiating depending on the combination, and the overall direction can be both systemic (with oral administration) and local (with external use). A common mechanism of synergy is the impact on the same or complementary signaling pathways, including NF-κB, MAPK, JAK/STAT, as well as the regulation of the production of inflammatory mediators and antioxidant factors.

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

Geography of use and traditional medicine — Millettia erythrocalyx

Millettia erythrocalyx is found in the forested areas of Southeast Asia, mainly in Thailand, Laos, Cambodia, and Vietnam, where it is included in regional herbal guides and ethnobotanical descriptions. In Thai traditional medicine, the plant was used primarily in the form of decoctions and alcohol infusions of bark and leaves, applied externally and internally as part of multicomponent mixtures. In the ethnobotanical practice of the peoples of northern Thailand, there are known cases of using powder of dried bark mixed with vegetable oils for treating skin. Vietnamese herbalists mention Millettia erythrocalyx in the context of bark-based remedies infused in rice wine, and in the form of decoctions for general health strengthening.

Ethnographic materials indicate the use of the plant in the cultures of the Khmu and Lao-Tai ethnic groups, where it was valued for the "power of the tree," and in some cases, the bark was used in ritual cleansing ceremonies associated with removing "bad energy." In some regions of Laos and northern Thailand, the plant appeared in rites of passage and seasonal ceremonies, where its branches were used as a talisman, strengthened above the entrance to a dwelling. In rural areas of Cambodia, the practice of fumigating with smoke from dried parts of the plant to repel insects and "cleanse" the space is mentioned.

Historical information on the use of Millettia erythrocalyx is fragmentary; the first written mentions are recorded in herbal guides from the late 19th – early 20th centuries, compiled by French colonial botanists and physicians working in Indochina. Data on use in other regions are limited, and outside Southeast Asia, the plant is found mainly in botanical collections and scientific publications on tropical flora.