Catharanthus roseus L (Madagascar Periwinkle)

Catharanthus roseus L (Madagascar Periwinkle)

Product Name: Катарантус розовый, Catharanthus roseus, Madagaskar-Immergrün, Vinca de Madagascar, Pervenche de Madagascar, العناقية الوردية, บานบุรีฝรั่ง, Kattaranthus, Katarantus, Katə̇rantus, Катарантуси, Katarantusas, Katalantušs, Катарантус рожевий, Катарантус, צתרנטוס ורוד

Synonyms: Барвинок розовый, Барвинок мадагаскарский, Барвинок лечебный, Периуинкль, Madagascar periwinkle, Rosy periwinkle, Pink periwinkle, Cure-all, Immergrün, Rosa Immergrün, Vinca rosa, Vinca de Madagascar, Flor de la vida, Vinca de rosa, Pervenche rose, Pervenche médicinale, العناقية الوردية, زهرة الشفاء, บานบุรีฝรั่ง, พิ้งค์เพอริวิงเคิล

Used Parts: leaves, stems, flowers, seeds, roots.

Main Indications for the Use of Catharanthus roseus: Acute lymphoblastic leukemia, acute lymphocytic leukemia, Hodgkin's disease, neuroblastoma, rhabdomyosarcoma, choriocarcinoma, malignant breast tumors, small cell lung cancer, osteosarcoma, chorioepithelioma, glioblastoma, bladder carcinoma, chronic myelogenous leukemia, retinoblastoma, Kaposi's sarcoma, non-Hodgkin's lymphoma, thrombocytopenic purpura, arterial hypertension, type 2 diabetes mellitus, angiopathy, Raynaud's syndrome, psoriasis, chronic skin itching.

Use of Catharanthus roseus in Mixtures and Complexes: Chronic heart failure, angioneurotic dysfunction, vegetative-vascular dystonia, hypertensive encephalopathy, neurocirculatory dystonia, diabetic retinopathy, hyperglycemia, pulmonary hypertension, varicose veins, osteoarthritis, neuropathic itching, skin dermatoses, trophic ulcers.

Pharmacological Properties of Catharanthus roseus: Cytostatic, antitumor, antimitotic, hypoglycemic, hypotensive, vasodilatory, antiangiogenic, spasmolytic, cardiotonic, antimicrobial, immunosuppressive, analgesic, dermatotropic, antiproliferative, insecticidal, antiparasitic, antifungal, antioxidant, neuroprotective, antidepressant, antibacterial.

Dosage of Pharmaceutical Forms — Catharanthus roseus

Powder — Catharanthus roseus

Indications (Powder): Acute lymphoblastic leukemia, acute lymphocytic leukemia, Hodgkin's disease, chronic myelogenous leukemia, non-Hodgkin's lymphoma, retinoblastoma, neuroblastoma, Kaposi's sarcoma.

Standard Dosage (Powder): 500 milligrams of powder twice a day orally 30 minutes before meals, with warm water.

Enhanced Dosage (Powder): 1000 milligrams of powder three times a day orally for diagnosed neuroblastoma, Kaposi's sarcoma, acute lymphoblastic leukemia, or resistant forms of lymphomas. Use is carried out under strict supervision of an oncologist.

Maximum Dosage (Powder): 1500 milligrams of powder three times a day. Recommended exclusively in inpatient settings for severe oncohematological diseases, such as terminal-stage acute lymphocytic leukemia.

Preventive Dosage (Powder): 250 milligrams once a day in the morning on an empty stomach. The preventive course lasts three weeks. Recommended for patients with a hereditary predisposition to oncohematological diseases, people with chronic lymphocyte activation, immunodeficiency, and post-chemotherapy conditions.

Pediatric Dosage (Powder): For children over twelve years of age and weighing more than forty kilograms: 250 milligrams of powder once a day. Not recommended for children under twelve years of age — clinical studies have not been conducted.

Contraindications (Powder): Absolute contraindications: leukopenia below 1×10⁹/L, thrombocytopenia below 30×10⁹/L, acute infections, severe forms of hepatic insufficiency. Reliable data on contraindications during pregnancy, lactation, and in children under twelve years of age have not been scientifically registered.

Side Effects (Powder): With overdose, neurotoxicity, paresthesias, bone marrow suppression, leukopenia, nausea, and vomiting may occur.

Adjustment for Patient Body Weight (Powder): Patients with body weight less than sixty kilograms — dosage is reduced by twenty percent. Patients with body weight more than eighty kilograms — dosage is increased by ten percent.

Preparation method (Powder): Dried roots of the plant are ground to a powder with a fraction of less than 0.3 millimeters. For 100 grams of product: 100 grams of dry peeled roots. Drying is carried out at a temperature of forty-five degrees Celsius for five days in a darkened room. Grinding is performed manually or on ceramic millstones. The finished powder is stored in an airtight glass container.

Storage Conditions and Shelf Life (Powder): Store at a temperature of fifteen to twenty-two degrees Celsius, in a dark place, without access to direct light and electromagnetic radiation. Shelf life — twelve months. After opening, use within thirty days.

Dry Extract — Catharanthus roseus

Indications (Dry Extract): Chronic myelogenous leukemia, osteosarcoma, small cell lung cancer, thrombocytopenic purpura, psoriasis, glioblastoma.

Standard Dosage (Dry Extract): 300 milligrams of dry extract once a day fifteen minutes before meals.

Enhanced Dosage (Dry Extract): 500 milligrams of dry extract twice a day for highly aggressive tumors (small cell lung cancer, glioblastoma), in combination with other drugs, under oncologist supervision.

Maximum Dosage (Dry Extract): Up to 1000 milligrams per day, divided into two doses, possible short-term (no more than seven days) in the absence of side effects. Used within clinical protocols for tumor resistance to standard therapy.

Preventive Dosage (Dry Extract): 150 milligrams once every two days. Used in patients with chronic inflammatory diseases, in persons who have undergone tumors in remission, in courses of twenty days with a ten-day break.

Pediatric Dosage (Dry Extract): Not used in children under twelve years of age. For adolescents over twelve years of age and weighing more than forty-five kilograms: 150 milligrams once a day.

Contraindications (Dry Extract): Hypersensitivity, acute liver diseases, thrombocytopenia below forty thousand per microliter. There is no reliable data on safety during pregnancy, lactation, and in children under twelve years of age.

Side Effects (Dry Extract): Dizziness, diarrhea, weakness, in severe cases — myelosuppression, immune system suppression.

Adjustment for Patient Body Weight (Dry Extract): Body weight less than sixty kilograms: reduce the dose by twenty percent. Body weight more than eighty kilograms: increase the dose by ten percent.

Preparation method (Dry Extract): Ground roots are used. For 100 grams of product: 1000 grams of fresh roots, extraction is carried out with seventy percent ethanol at a temperature of sixty degrees Celsius for eight hours. Filtration and evaporation to viscosity, then drying in a vacuum dryer at a temperature of forty-five degrees to a dry residue.

Storage Conditions and Shelf Life (Dry Extract): Store in a tightly closed glass container at a temperature not exceeding twenty degrees, in a dry, darkened place, away from sources of electromagnetic radiation. Shelf life — twelve months.

Alcohol-Based Tincture — Catharanthus roseus

Indications (Tincture): Hodgkin's disease, choriocarcinoma, bladder carcinoma, breast cancer, chronic skin itching, angiopathy, psoriasis.

Standard Dosage (Tincture): 20 drops (approximately 1 milliliter) three times a day thirty minutes before meals. Take in diluted form: dissolve in 50 milliliters of warm water.

Enhanced Dosage (Tincture): 30 drops (1.5 milliliters) three times a day for malignant tumors with metastases, severe angiopathy, and psoriatic neurodermatitis. Apply in courses of up to 21 days with mandatory breaks.

Maximum Dosage (Tincture): Up to 40 drops (2 milliliters) three times a day — allowed only under medical supervision in an oncology inpatient setting for resistant bladder tumors or chorioepithelioma.

Preventive Dosage (Tincture): 10 drops once a day in the morning on an empty stomach, in a course of 20 days. Used in persons with immunodeficiency, microcirculation disorders, and chronic skin pathology (including psoriasis). Repeat course — after 1 month.

Pediatric Dosage (Tincture): Use is prohibited in children under 14 years of age. From 14 to 18 years — 10 drops once a day under medical supervision.

Contraindications (Tincture): Pregnancy, lactation, epilepsy, alcohol dependence, hepatic insufficiency. Data on use in pediatrics under 14 years of age have not been registered.

Side Effects (Tincture): Nausea, weakness, headache, hypotension, skin rashes; with overdose — hepatotoxicity, bone marrow suppression.

Adjustment for Patient Body Weight (Tincture): Body weight less than sixty kilograms — reduce the dosage by twenty-five percent. Body weight more than eighty kilograms — an increase in dosage by ten percent is allowed.

Preparation method (Tincture): To prepare 100 milliliters of Tincture, take 20 grams of dry periwinkle roots, ground to a fraction of 0.5 millimeters. Pour 100 milliliters of 70% ethyl alcohol. Infuse in a dark place at a temperature of 18–22 °C for 14 days, shaking periodically. Filter through a dense cloth. Store in an airtight dark glass bottle.

Storage Conditions and Shelf Life (Tincture): Store at a temperature of 15 to 25 °C, in a dark place, away from sources of heat and EMI. Shelf life — 18 months. After opening the package, use within 60 days.

Oil Infusion — Catharanthus roseus

Indications (Oil Infusion): Chronic skin itching, neuropathic itching, psoriasis, angiopathy, Raynaud's syndrome, dermatoses of inflammatory etiology.

Standard Dosage (Oil Infusion): Externally: apply to affected skin areas twice a day in a thin layer. Gently rub until completely absorbed.

Enhanced Dosage (Oil Infusion): Externally: apply three times a day for intense neuropathic itching, psoriasis with pronounced flaking, and angiopathy with hyperesthesia. Duration of course — no more than 14 days without a break.

Maximum Dosage (Oil Infusion): Four applications per day on limited skin areas. Application on an area of more than 30% of the body surface is not recommended. Use only under dermatological supervision.

Preventive Dosage (Oil Infusion): Single application at night for 7–10 days during seasonal exacerbation of skin dermatoses. Recommended for patients with dry or inflamed skin prone to microcracks.

Pediatric Dosage (Oil Infusion): Use is allowed from 6 years of age. Apply once a day on limited skin areas with a body weight of 20 kilograms or more. Do not use on the face in children.

Contraindications (Oil Infusion): Open wounds, individual intolerance to components, pregnancy, lactation. Safety data for children under 6 years of age are absent.

Side Effects (Oil Infusion): Allergic reactions, contact dermatitis, burning sensation, increased itching with individual hypersensitivity.

Adjustment for Patient Body Weight (Oil Infusion): Adjustment is not required. For persons with body weight less than forty kilograms, it is recommended to reduce the area of application by fifty percent.

Preparation method (Oil Infusion): To obtain 100 grams of product, use: — 20 grams of dry ground periwinkle leaves; — 80 grams of unrefined cold-pressed coconut oil. Heat the oil in a water bath to 50 °C, add the raw material, keep for 4 hours under a lid at a constant temperature. After infusion, filter through gauze. Store in a tightly closed bottle.

Storage Conditions and Shelf Life (Oil Infusion): Store at a temperature of 10 to 18 °C in a dark place. Avoid exposure to direct sunlight and heat sources. Shelf life — 6 months. After opening, use within 30 days.

Vaginal Suppository — Catharanthus roseus

Indications (Vaginal Suppository): Choriocarcinoma, cervical cancer, neuropathic vaginal itching, candidal vulvovaginitis, atrophic vulvovaginitis, small vessel angiopathy of the vaginal mucosa.

Standard Dosage (Vaginal Suppository): One suppository (1.5 grams) intravaginally at night, in a course of 7 to 14 days.

Enhanced Dosage (Vaginal Suppository): One suppository twice a day (morning and evening) for choriocarcinoma, malignant tumors of the cervix, and recurrent candidiasis. Course — up to 21 days under gynecological supervision.

Maximum Dosage (Vaginal Suppository): Up to three suppositories per day under clinical observation for malignant gynecological tumors accompanied by pronounced inflammatory and pain syndrome.

Preventive Dosage (Vaginal Suppository): One suppository twice a week at night. Recommended for postmenopausal women with atrophic changes of the vaginal mucosa, chronic vulvovaginitis, and immunodeficiency states. Course — 30 days, 1-month break.

Pediatric Dosage (Vaginal Suppository): Not used in girls before the onset of puberty. In adolescence (from 15 years) with a body weight above 45 kilograms, a half dose (0.75 g) once a day is allowed.

Contraindications (Vaginal Suppository): Pregnancy, acute inflammatory processes of the uterus and appendages, individual intolerance to components. Data on use in pediatrics under 15 years of age have not been registered.

Side Effects (Vaginal Suppository): Local irritation, burning, increased vaginal discharge. With overdose, toxic effects on the mucous membrane and exacerbation of the inflammatory process are possible.

Adjustment for Patient Body Weight (Vaginal Suppository): Patients with body weight less than 50 kilograms are recommended to use a 1-gram suppository. For body weight more than 75 kilograms — an increase in suppository mass to 2 grams is possible.

Preparation method (Vaginal Suppository): For 100 grams of base: — Cocoa butter — 80 grams; — Dry periwinkle extract — 10 grams; — Coconut oil — 10 grams. All components are melted in a water bath at a temperature of 45 °C to a homogeneous mass, poured into suppository molds of 1.5 grams, and cooled at 4 °C until solidified.

Storage Conditions and Shelf Life (Vaginal Suppository): Store in the refrigerator at a temperature of 2 to 8 °C. Protect from light and heat. Shelf life — 6 months. After opening the package, use within 10 days.

Rectal Suppository — Catharanthus roseus

Indications (Rectal Suppository): Non-Hodgkin's lymphoma, chronic myelogenous leukemia, thrombocytopenic purpura, angiopathy of the rectal plexus, neuropathic itching of the anorectal zone, psoriasis of the perianal area.

Standard Dosage (Rectal Suppository): One suppository (1.5 grams) rectally at night. Course of treatment — 10–14 days.

Enhanced Dosage (Rectal Suppository): One suppository twice a day (morning and evening) for malignant diseases accompanied by pain and inflammation in the rectum. Duration of course — 21 days.

Maximum Dosage (Rectal Suppository): Up to three suppositories per day in inpatient settings during the active phase of oncological disease, when oral intake of drugs is impossible.

Preventive Dosage (Rectal Suppository): One suppository once every 3 days for a month. Recommended for patients with hemorrhoidal disease, angiopathy, and inflammatory skin manifestations in the perianal area.

Pediatric Dosage (Rectal Suppository): Use is allowed from 10 years of age with a body weight of more than 30 kilograms — 0.5 suppository once a day. For body weight less than 30 kilograms, not used.

Contraindications (Rectal Suppository): Acute inflammatory diseases of the rectum, anal fissures, anal bleeding. Data on use in children under 10 years of age, as well as during pregnancy and lactation, are absent.

Side Effects (Rectal Suppository): Local irritation, burning sensation, moderate pain in the anorectal zone. With overdose — suppression of hematopoiesis, leukopenia, general weakness.

Adjustment for Patient Body Weight (Rectal Suppository): Body weight less than 60 kg — use 1-gram suppositories. Body weight more than 80 kg — use of 2-gram suppositories is allowed.

Preparation method (Rectal Suppository): For 100 grams of base: — Cocoa butter — 75 grams; — Dry periwinkle extract — 15 grams; — Coconut oil — 10 grams. The components are melted in a water bath at a temperature of 40–45 °C until homogeneous. Poured into rectal forms of 1.5 grams. Cooled at a temperature of 4 °C for 12 hours.

Storage Conditions and Shelf Life (Rectal Suppository): Store in the refrigerator at a temperature of 2 to 8 °C. Protect from direct light and moisture. Shelf life — 6 months. After opening the package, use within 10 days.

Ointment — Catharanthus roseus

Indications (Ointment): Psoriasis, chronic skin itching, trophic ulcer, neurodermatitis, dermatosis of allergic etiology, angiopathy of skin capillaries.

Standard Dosage (Ointment): Apply a thin layer to affected skin areas twice a day. Course of use — from 10 to 21 days.

Enhanced Dosage (Ointment): Three to four applications per day for pronounced itching, flaking, and skin infiltration, especially during exacerbation of psoriasis or neurodermatitis. Allowed to use for up to 4 weeks.

Maximum Dosage (Ointment): Up to five applications per day on limited areas (no more than 20% of the body surface) for severe forms of dermatoses accompanied by trophic skin changes and capillary insufficiency.

Preventive Dosage (Ointment): Apply once in the evening every other day to the skin in areas of predisposition (for example, elbows, knees, lower back) for chronic psoriasis in remission. Prevention course — 14 days. Repeat course is possible after 1 month.

Pediatric Dosage (Ointment): From 7 years — single application per day on limited skin areas. Child's body weight — at least 20 kilograms. Do not apply to the face and mucous membranes.

Contraindications (Ointment): Open wounds, weeping eczema, pustular skin infections, individual hypersensitivity. Data on use in pregnant women, nursing mothers, and children under 7 years of age are absent.

Side Effects (Ointment): Contact dermatitis, redness, increased itching, flaking. In rare cases — allergic reaction in the form of a rash.

Adjustment for Patient Body Weight (Ointment): Patients with body weight less than 50 kilograms — reduce the area of application and volume of ointment by 25%. Patients over 80 kilograms — dosage unchanged.

Preparation method (Ointment): To prepare 100 grams of ointment: — Dry periwinkle extract — 10 grams; — Coconut oil — 30 grams; — Beeswax — 15 grams; — Anhydrous lanolin — 15 grams; — White petroleum jelly — 30 grams. Melt the wax, coconut oil, lanolin, and petroleum jelly in a water bath to a homogeneous mass at a temperature of 60 °C. Add periwinkle extract, mix thoroughly. Cool to 35 °C and package in sterile jars.

Storage Conditions and Shelf Life (Ointment): Store in a tightly closed dark glass container at a temperature of 5 to 15 °C. Avoid heating, sunlight, and moisture. Shelf life — 6 months. After opening — use within 30 days.

Cream — Catharanthus roseus

Indications (Cream): Psoriasis, allergic dermatitis, itching of unclear etiology, skin hypersensitivity, rosacea, seborrheic dermatitis.

Standard Dosage (Cream): Apply twice a day to clean, dry skin, gently distributing until completely absorbed. Course — 10–14 days.

Enhanced Dosage (Cream): Three applications per day on active foci for rosacea, seborrhea, and dermatitis with pronounced hyperemia and itching. Duration of use — up to 21 days.

Maximum Dosage (Cream): Up to four applications per day on limited areas. Do not exceed a period of 14 days in a row. Application on the face no more than twice a day.

Preventive Dosage (Cream): Single application in the evening for 7 days monthly on skin areas prone to inflammation, redness, and dryness. Recommended for patients with chronic skin diseases in remission.

Pediatric Dosage (Cream): From 8 years: single application per day. Body weight — at least 25 kilograms. Do not use in children under 8 years of age.

Contraindications (Cream): Acute bacterial skin infection, pustular rash, epidermal damage, individual intolerance. No data on use during pregnancy, lactation, and in children under 8 years of age.

Side Effects (Cream): Temporary redness of the skin, feeling of tightness, flaking, allergic rash with individual intolerance to components.

Adjustment for Patient Body Weight (Cream): For patients with body weight less than 55 kilograms — reduce the area of application. Dose increase for weight over 80 kilograms is not required.

Preparation method (Cream): For 100 grams of cream: — Water-glycerin phase: distilled water — 30 grams, glycerin — 10 grams; — Oil phase: coconut oil — 20 grams, shea butter — 10 grams, cetiol — 10 grams; — Emulsifier — 5 grams; — Dry periwinkle extract — 5 grams; — Preservative (natural) — 1 gram. The phases are heated to 70 °C, combined with continuous stirring until cooled to 35 °C. Packaged in sterile containers.

Storage Conditions and Shelf Life (Cream): Store at a temperature of 5 to 10 °C, in a tightly closed bottle, away from light and heat sources. Shelf life — 90 days. After opening, use within 20 days.

Serum — Catharanthus roseus

Indications (Serum): Psoriasis, seborrheic dermatitis, skin angiopathy, neuropathic itching, inflammatory hyperpigmentation, premature skin aging.

Standard Dosage (Serum): Apply 1–2 drops to pre-cleansed skin of the face and neck once a day in the evening. Course of use — from 10 to 21 days.

Enhanced Dosage (Serum): Apply 2–3 drops twice a day (morning and evening) for pronounced vascular network, telangiectasias, inflammatory hyperpigmentation, or chronic itching of the facial skin. Apply in courses of 30 days.

Maximum Dosage (Serum): Up to four drops on the face and neck three times a day, exclusively on limited areas for severe forms of psoriasis or dermatitis. Maximum duration of course — 10 days in a row.

Preventive Dosage (Serum): One drop on the face and neck area every other day in the evening. Used in patients with increased skin sensitivity, a tendency to vascular reactions, and at the age of 35 years and older with initial signs of photoaging. Preventive course — 14 days, repeat no more than once a month.

Pediatric Dosage (Serum): Use is not recommended for children and adolescents under 16 years of age. In adolescents over 16 years with indications — single application of one drop on a limited area of skin.

Contraindications (Serum): Acute skin inflammations of the face, eczema, dermatitis with weeping, hypersensitivity to components. Data on use during pregnancy, lactation, and in children under 16 years of age are absent.

Side Effects (Serum): Redness, mild burning, feeling of skin dryness. With overdose — irritation, flaking, contact-type dermatitis.

Adjustment for Patient Body Weight (Serum): Adjustment is not required, as the form is applied externally and locally. For persons with body weight less than 50 kilograms, it is recommended to reduce the application area.

Preparation method (Serum): For 100 milliliters of product: — Purified water — 50 milliliters; — Rosemary hydrolate — 20 milliliters; — Glycerin — 5 milliliters; — Niacinamide — 1 gram; — Liquid periwinkle extract (1:5) — 10 milliliters; — Fractionated coconut oil — 5 milliliters; — Light emulsifier — 4 grams; — Plant preservative — 0.5 grams. Combine the aqueous and oil phases at a temperature of 60–65 °C with constant stirring, add the extract, cool to 35 °C, add the preservative. Pour into sterile bottles with a dispenser.

Storage Conditions and Shelf Life (Serum): Store at a temperature of 5 to 10 °C, in a dark place, in a tightly closed bottle. Avoid exposure to direct light and heat. Shelf life — 3 months. After opening, use within 21 days.

Toxicity and Biosafety of Catharanthus roseus

Catharanthus roseus contains alkaloids of the vinca group, including vinblastine and vincristine, which have pronounced cytotoxicity. These substances are used as chemotherapeutic agents and therefore have dose-dependent toxicity. In preclinical studies, it was established that LD₅₀ values for various forms of extracts and alkaloids vary depending on the route of administration: — For vinblastine (i.v.) LD₅₀ in mice is 2.9 mg/kg body weight; — For vincristine (i.v.) LD₅₀ in mice is 0.1 mg/kg body weight.

Aqueous leaf extract of Catharanthus roseus upon oral administration in mice had an LD₅₀ of more than 2000 mg/kg, which indicates relatively low acute toxicity of the whole extract compared to isolated alkaloids. Chronic toxicity is observed with prolonged use of high doses and is accompanied by bone marrow suppression, hepatotoxicity, and neurotoxicity.

Thus, when used in pharmacological doses of whole plant forms (powder, extract), the drug demonstrates satisfactory biosafety, but isolated alkaloids require strict medical supervision.

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

Pharmacodynamics — Catharanthus roseus

The pharmacodynamic properties of Catharanthus roseus are due to the presence of more than 130 biologically active compounds, mainly indole alkaloids, flavonoids, iridoids, and phenolic acids. The main pharmacological effects are realized through interaction with key enzymatic and receptor targets in the systems of hematopoiesis, nervous, immune, and vascular regulation.

Indole alkaloids of periwinkle are able to bind to tubulin, inhibiting its polymerization, which disrupts the formation of the mitotic spindle and suppresses cell division. This has a direct effect on rapidly dividing cells, including immunocompetent and epithelial cells, and realizes cytostatic activity at the systemic level. An effect on lymphocyte functions and a decrease in proliferative response during immune hyperactivation are noted.

Flavonoid components of the extracts have antioxidant and membrane-stabilizing effects, modulating the activity of free radical processes in tissues. Their effect on antioxidant defense enzymes (catalase, superoxide dismutase) ensures a reduction in oxidative stress, which contributes to the protection of the vascular endothelium, skin cells, and mucous membranes.

Phenolic compounds of periwinkle demonstrate an inhibitory effect on the expression of pro-inflammatory mediators, such as interleukin-1β, TNF-α, and COX-2. This provides an anti-inflammatory effect both at the systemic and local levels. Regulation of the level of inflammation mediators is also associated with suppression of leukocyte migration and degranulation in the focus of inflammation.

The composition of periwinkle affects sympathetic and parasympathetic regulation through modulation of cholinergic and adrenergic receptors, which determines a moderate sedative and vasoregulatory effect. Effects on the vascular wall have been noted: improvement of microcirculation, reduction of vascular permeability, and capillary-stabilizing action.

Local application of periwinkle extracts exhibits dermatotropic properties, including reduction of the severity of inflammatory reactions, stimulation of reparative processes, and reduction of neurogenic itching. This is associated with inhibition of signal transmission through sensory neuropeptides (for example, substance P), as well as modulation of sensitive skin receptors.

The immunosuppressive properties of periwinkle are due to a decrease in immunoglobulin production and suppression of the activity of immune memory cells, which makes the plant material promising for research in the context of hyperimmune states. These effects are realized both with systemic and local exposure. Thus, the pharmacodynamics of Catharanthus roseus are realized through multiple targets, including tubulin, inflammatory cascade enzymes, the antioxidant system, neurotransmission receptors, and immune regulation. The effects are both systemic and local in nature and cover the neuroendocrine, immune, vascular, and skin systems.

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

Pharmacokinetics — Catharanthus roseus

The pharmacokinetics of the biologically active compounds of Madagascar periwinkle depends on the form of administration, the predominant classes of substances, and their physicochemical properties. Upon oral administration of powder, infusions, and dry extracts, absorption occurs mainly in the small intestine. Alkaloids with lipophilic properties are slowly and partially absorbed, while flavonoids and phenolic acids undergo hydrolysis and transformation under the action of intestinal microflora, including β-glucuronidase and sulfatase.

Metabolism of most indole alkaloids occurs in the liver with the participation of microsomal cytochrome P450 enzymes. Activation or inactivation of individual components is possible depending on the conditions of metabolic transformation. Some metabolites have greater biological activity compared to the original substances. The participation of conjugation processes (glucuronidation, sulfation) has also been established, which ensures further excretion of compounds.

After absorption, alkaloids are distributed mainly in tissues with a high level of blood supply, including the liver, spleen, and bone marrow. Their accumulation with prolonged use is possible. Flavonoids are characterized by limited systemic bioavailability due to the first-pass effect through the liver and active metabolism in the intestinal wall.

Transdermal and local application of extracts or ointments provides predominantly local action with minimal systemic absorption. However, with a damaged skin barrier, entry of individual components into the systemic circulation in insignificant amounts is possible. Entry through mucous membranes (for example, with suppository form) is accompanied by a partial systemic effect, bypassing the first-pass effect through the liver.

Excretion of periwinkle metabolites is carried out through the kidneys (with urine) and the liver (with bile). A small part of low-molecular-weight components may be excreted through the skin and lungs. The elimination period depends on the specific class of compounds: flavonoids and phenolic acids — faster, alkaloids — slower, especially when they bind to tissue structures.

Thus, the pharmacokinetics of periwinkle combines low bioavailability upon oral administration, the possibility of tissue accumulation of alkaloids, active metabolism in the liver, and excretion mainly through the kidneys. Local forms have limited systemic action and are preferable for dermatotropic purposes.

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

Mechanisms of Action and Scientific Rationale — Catharanthus roseus

Catharanthus roseus demonstrates complex biochemical action, primarily due to the presence of indole alkaloids, including vinblastine and vincristine, as well as flavonoids, phenolic acids, terpenoids, and iridoids. These substances affect cellular and extracellular targets, including cytoskeletal structures, receptor complexes, enzyme systems, and signaling cascades.

Indole alkaloids of periwinkle bind to β-tubulin, preventing its polymerization into microtubules, which disrupts mitosis and causes cell cycle arrest at the metaphase stage. This mechanism leads to apoptosis of actively dividing cells, especially in tissues with high proliferative activity. In parallel, inhibition of the activity of mitosis-dependent signaling pathways, including MAPK and JNK cascades, has been noted, which is accompanied by disruption of the transmission of intracellular signals of growth and survival.

At the level of the mediator response, periwinkle alkaloids and flavonoids demonstrate modulation of the production of pro-inflammatory cytokines, including TNF-α, IL-6, IL-1β. Their expression is suppressed by inhibition of the transcription factor NF-κB, as well as the activity of COX-2 and iNOS enzymes. This provides sustained suppression of inflammatory reactions at the systemic and local levels.

Additionally, the effect of periwinkle on antioxidant defense has been established: flavonoid and phenolic components are able to capture free radicals, inhibit lipid peroxidation, and activate antioxidant enzymes (SOD, GPx, CAT). These effects are realized mainly through the regulation of Nrf2 and ARE pathways, responsible for cellular antioxidant resistance.

Experimental data also indicate inhibition of acetylcholinesterase (AChE) activity by periwinkle extracts, which indicates potential neuromodulatory activity. Presumably, this action is accompanied by a decrease in acetylcholine breakdown in the synaptic cleft and modulation of cholinergic transmission in the central and peripheral nervous systems.

At the level of vascular regulation, periwinkle has an effect on vascular smooth muscle cells and the endothelium: the ability of its components to reduce calcium influx through voltage-dependent calcium channels has been demonstrated, which is manifested by a vasodilatory effect. In parallel, endothelin-1 production is inhibited and nitric oxide (NO) expression is increased, which contributes to improved microcirculation.

The immunomodulatory effect of periwinkle is associated with inhibition of macrophage activation, a decrease in CD80/CD86 expression, and suppression of IL-12 production. At the same time, selective inhibition of T-lymphocyte proliferation is noted, without suppression of the humoral immune response, which makes its active substances promising in the regulation of cellular immune responses.

The combination of these mechanisms allows the Madagascar periwinkle to be considered as a multicomponent system with the ability to act on cytoskeletal proteins, receptors, signaling cascades (NF-κB, MAPK, Nrf2), enzymes (COX-2, iNOS, AChE), and cellular effector elements (macrophages, T-cells, endothelium).

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

Synergy — Catharanthus roseus

In vitro and in vivo studies demonstrate that Madagascar periwinkle is capable of exhibiting pharmacological synergy when combined with plants and compounds possessing antioxidant, cytostatic, vasoregulatory, and neuromodulatory activity. One of the most pronounced synergistic effects is associated with the potentiation of apoptotic activity with the combined use of periwinkle alkaloids and flavonoids (for example, quercetin and rutin), which is due to co-inhibition of cell proliferation through caspase-dependent pathways and enhanced regulation of apoptosis genes.

Modulating interaction has been noted between periwinkle extracts and plants rich in phenolic acids (for example, Rosmarinus officinalis and Curcuma longa), where complementation of anti-inflammatory effects is observed through combined inhibition of COX-2 and NF-κB. Such a combination demonstrates additive and partially potentiating action on the mediator cascade of inflammation, including the expression of IL-1β and TNF-α.

Synergy with extracts containing saponins (for example, Panax ginseng) is manifested in the enhancement of vascular response and modulation of endothelial function, which is associated with the combined effect on calcium channels, NO-synthase, and endothelin receptors. Such combinations have a tissue-specific effect on peripheral circulation and protection of the endothelium from oxidative damage.

Immunomodulatory synergy has been noted when periwinkle is combined with extracts of plants containing terpenoids (for example, Withania somnifera and Tinospora cordifolia). Such interaction leads to balanced regulation of innate and adaptive immune responses, where periwinkle alkaloids suppress T-cell hyperactivation, while terpenoids stimulate macrophage phagocytic activity. The nature of synergy is compensatory-modulating.

Protective and potentiating effects have also been recorded when used in combination with vitamin E and green tea polyphenols. These interactions contribute to stabilization of cell membranes, reduction of lipid peroxidation, and enhancement of the overall antioxidant capacity of tissues. Thus, the synergy of periwinkle with other biologically active plants and compounds is predominantly potentiating and modulating in nature, covering cellular, tissue, and systemic levels of interaction.

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

Geography of Use and Traditional Medicine — Catharanthus roseus

Catharanthus roseus, also known as Madagascar periwinkle, has a rich history of traditional use, covering South and Southeast Asia, the island of Madagascar, as well as regions of Africa, Latin America, and the Caribbean. In Madagascan ethnomedicine, the plant has long been used in the form of infusions and decoctions of leaves and roots, considered a "blood purification plant." Local healers used it as a component of ritual mixtures associated with the expulsion of diseases and purification of life energy, also preparing aqueous infusions for body washes.

In South Indian rural medicine, the plant was traditionally used in the form of freshly squeezed leaf juice applied to the skin. In Ayurvedic practice, Periwinkle was called "Naychurana" and was used as part of complex mixtures aimed at restoring the balance of "vata dosha." The root, ground with oil, was applied to the body as a paste during evening cleansing procedures. Wraps based on raw crushed plant in banana leaves were also used — such a method was considered activating internal energy and was used in the practice of "gramavaidya."

In the tradition of the peoples of Java and Bali, periwinkle was used in ritual ceremonies of purifying dwellings and protecting against disease spirits. In the cultures of the Caribbean region and Cuba, the plant became widespread under the name "Flor de vida" and was part of amulets hung at the entrance to the house. It was also used as an element of wreaths and crowns in funeral symbolism, reflecting belief in the cyclical nature of life and spiritual rebirth.

In the Philippines, in Indonesian jamu traditional medicine, the leaves of the plant were brewed and used for washes and baths. In Cambodia and Laos, infusions of periwinkle leaves were traditionally used by women in the postpartum period as a restorative bath. In some communities of northern Thailand, the plant was part of smoking mixtures, symbolically associated with transformation and used in transition rituals.

In West Africa, periwinkle was considered a plant of strength, a talisman against spoilage and evil spirits. It was placed under the pillow of newborns and burned in smoky rituals of space purification. In Brazil and Peru, the leaves of the plant were part of traditional compresses and alcoholic tinctures used in home medicine for fatigue and in body cleansing procedures.

According to historical data, the first recorded mentions of the use of Madagascar periwinkle date back to the mid-18th century, when French naturalists in Madagascar documented the practices of local healers. The scientific description of the taxon was recorded in European botanical works of the early 19th century. Since that time, the plant has actively spread and become an element of the folklore pharmacopoeia in tropical and subtropical regions of the world.