​Annona muricata (Soursop / Prickly Custard Apple)

Annona muricata (Soursop / Prickly Custard Apple)

Product Name: Аннона колючая, Annona muricata, Stachelannone, Guanábana, Corossolier, شجرة الجرافيولا, ทุเรียนเทศ

Synonyms: Аннона колючая, Грабиола, Сорсоп, Гуанабана, Soursop, Graviola, Prickly Custard Apple, Stachelannone, Stachelannona, Guanábana, Anona agria, Corossol, Corossolier, شجرة الجرافيولا, شجرة سورسوب, ทุเรียนเทศ, น้อยหน่าเทศ, ทุเรียนน้ำ

Main Indications for Annona muricata Use: Pancreatic neuroendocrine tumor, hepatocellular carcinoma, breast cancer, prostate cancer, cervical cancer, chronic gastritis, colitis, arterial hypertension, type 2 diabetes, depressive disorder, anxiety disorder, insomnia, helminthiasis, trypanosomiasis, leishmaniasis, candidiasis of the skin and mucous membranes.

Use of Annona muricata in mixtures and complexes: Neurodegenerative diseases, Parkinson's disease, pancreatitis, metabolic syndrome, gastric ulcer, migraine, chronic fatigue syndrome, herpesvirus infection, prostatic hyperplasia, irritable bowel syndrome.

Pharmacological Properties of Annona muricata: antitumor, antimicrobial, anthelmintic, antiprotozoal, sedative, anxiolytic, antidepressant, antioxidant, hypotensive, hypoglycemic, hepatoprotective, spasmolytic, antipyretic, diuretic.

Pharmaceutical Forms and Dosages of Annona muricata

Powder — Annona muricata

Standard Dosage (Powder): Take 1000–1500 mg 30 minutes before meals, 2 times a day. Does not require fat support. Standard course — 14 days.

Enhanced Dosage (Powder): 2000 mg 30 minutes before meals, 2 times a day. Without fat support. Course — 10 days.

Maximum Dosage (Powder): Maximum daily dose — 5000 mg. Take 2500 mg 2 times a day. Permissible duration — up to 5 days.

Adjustment for Patient Body Weight: Approximate dosage — 20 mg/kg body weight per day.

Pediatric Dosage (Powder): Use is permissible from 12 years of age. Starting dose — 500 mg 1–2 times a day, under supervision.

Preventive Dosage (Powder): Recommended for adults with a history of cancer and at-risk patients. Dose — 1000 mg per day, in courses of 10 days with a 20-day break.

Lethal Dose LD₅₀: According to animal data: about 1500 mg/kg orally. Reference: https://pubmed.ncbi.nlm.nih.go...

Storage Conditions and Shelf Life (Powder): Store in an airtight glass container shielded with foil, at a temperature of +5...+25 °C and humidity not exceeding 60%. Shelf life — up to 2 years.

Dry Extract — Annona muricata

Standard Dosage (Dry Extract): Take 500–800 mg during meals 2 times a day. Fat support is not required. Course — 14 days.

Enhanced Dosage (Dry Extract): 1000 mg 2 times a day, during meals. Course — 10 days.

Maximum Dosage (Dry Extract): Maximum permissible dose — 3000 mg per day, 1000 mg 3 times a day. Maximum course — 5 days.

Adjustment for Patient Body Weight: Recommended dose — 10–15 mg/kg body weight per day.

Pediatric Dosage (Dry Extract): Use is permissible from 12 years of age, no more than 300 mg 2 times a day. Tolerance monitoring is mandatory.

Preventive Dosage (Dry Extract): For elderly and debilitated patients — 500 mg once a day, in courses of 10 days. Repeat after 3–4 weeks.

Lethal Dose LD₅₀: Estimated — about 1000 mg/kg body weight (mice). Reference: https://www.ncbi.nlm.nih.gov/p...

Storage Conditions and Shelf Life (Dry Extract): Store in a tightly sealed glass container shielded from EMI, at a temperature of +5...+25 °C and humidity up to 50%. Shelf life — up to 3 years.

Tincture — Annona muricata

Limitations of use (Tincture): Contraindicated in epilepsy, Parkinson's disease, chronic liver failure, pregnancy and lactation.

Standard Dosage (Tincture): 20–25 drops (about 1 ml) 2 times a day, 15 minutes before meals. Does not require fat support. Course — 10 days.

Enhanced Dosage (Tincture): 1.5 ml (30 drops) 3 times a day. Course — 7 days.

Maximum Dosage ( Tincture): Up to 6 ml per day, no more than 5 days in a row. Requires assessment of the body's reaction.

Adjustment for Patient Body Weight: Approximately — 0.1 ml/kg body weight per day.

Pediatric Dosage (Tincture): Contraindicated under 14 years of age.

Preventive Dosage (Tincture): For adults with a history of cancer — 1 ml per day, in courses of 7 days, no more than once a month.

Lethal Dose LD₅₀: Insufficient data. For acetogenins: toxicity is high when exceeding doses. Requires an individual approach. Reference: https://www.ncbi.nlm.nih.gov/p...

Preparation method (Tincture): Ground dry leaves (1 part) are poured with 40% ethanol (5 parts), infused for 40 days in a dark place, in a shielded glass container, with daily shaking. EMI is excluded.

Storage Conditions and Shelf Life (Alcohol Tincture): Store in an airtight dark glass container shielded with foil. Without filtration. Temperature +5...+20 °C. Shelf life — up to 5 years.

Aqueous Infusion — Annona muricata

Indications for preferred use (Aqueous Infusion): Preferred for acute inflammatory diseases of the stomach, intestines and liver, for high fever, in a weakened state.

Standard Dosage (Aqueous Infusion): 100 ml 2 times a day, before meals. Infusion temperature — +36...+38 °C. Course — 7–10 days.

Enhanced Dosage (Aqueous Infusion): 150 ml 3 times a day, 15 minutes before meals. Course — 5–7 days.

Maximum Dosage (Aqueous Infusion): Up to 600 ml per day. Duration no more than 5 days in a row.

Adjustment for Patient Body Weight: Approximately — 6 ml/kg body weight per day.

Pediatric Dosage (Aqueous Infusion): From 7 years of age: 50 ml 1–2 times a day. Temperature +36 °C. Course — up to 5 days.

Preventive Dosage (Aqueous Infusion): For adults and the elderly — 100 ml once a day, course 7 days, repeat after 3 weeks.

Lethal Dose LD₅₀ (Aqueous Infusion): Not established. Toxic effects of aqueous forms are extremely low.

Preparation method (Aqueous Infusion): Dry leaves (10 g) are poured with 200 ml of hot water (+90 °C), infused for 40 minutes in a thermos. Avoid contact with metals and sources of EMI.

Storage Conditions and Shelf Life (Aqueous Infusion): Up to 24 hours at a temperature of +2...+8 °C in a glass container. Heat before taking to +36...+38 °C.

Oil Infusion — Annona muricata

Indications for use (Oil Infusion): External otitis, neurodermatitis, fungal skin infection, irritation of the ear canal, postherpetic neuralgia, recurrent rhinitis.

Standard Dosage (Oil Infusion): Intranasally: 1–2 drops in each nostril 2 times a day. Ear application — 1 drop in the affected ear 1–2 times a day. Course — up to 7 days.

Enhanced Dosage (Oil Infusion): Nasal — up to 3 drops 3–4 times a day. Ear application — up to 3 drops 3 times a day. Course — no more than 5 days.

Maximum Dosage (Oil Infusion): No more than 4 instillations per day. Duration no more than 5 days without medical supervision.

Adjustment for Patient Body Weight: In children, body weight is taken into account when choosing the frequency and volume.

Pediatric Dosage (Oil Infusion): From 3 years of age: 1 drop 1–2 times a day, no more than 5 days.

Preventive Dosage (Oil Infusion): Nasally — 1 drop in each nostril before going into a dusty environment. Ear — after swimming. Course — 3–5 days.

Preparation method (Oil Infusion): Dry ground leaves (1 part) are poured with warm sesame oil (5 parts), infused for 14 days in a dark place, shaken daily. Infusion temperature — up to +50 °C. Then filtered.

Storage Conditions and Shelf Life (Oil Infusion): Store in a dark glass container shielded with foil. Temperature +5...+20 °C. Shelf life — up to 6 months.

Ointment — Annona muricata

Indications for use (Ointment): Herpetic eruptions, fungal skin infection, post-burn scars, infiltrates, dermatitis.

Standard Dosage (Ointment): Apply a thin layer without rubbing 2 times a day. When applying a bandage — exposure up to 4 hours. Course — 5–10 days.

Enhanced Dosage (Ointment): Apply 3 times a day to a larger area. Course — up to 7 days. Monitoring of skin reaction is mandatory.

Maximum Dosage (Ointment): No more than 4 applications per day, on an area of no more than 30% of the body surface. Course — no more than 10 days.

Adjustment for Patient Body Weight: In children and with low body weight — reduction of the application area and frequency.

Pediatric Dosage (Ointment): From 5 years of age. Avoid applying to the face and mucous membranes. Frequency — 1–2 times a day.

Preventive Dosage (Ointment): For chronic dermatitis — in courses of 5 days during periods of exacerbation. Apply once a day.

Preparation method (Ointment): Base — beeswax (1 part) and olive oil (4 parts). Add oil infusion or soursop powder. Everything is melted in a water bath to +60 °C, mixed, cooled, packaged.

Storage Conditions and Shelf Life (Ointment): In a glass container shielded with foil, at a temperature of +4...+8 °C. Shelf life — up to 2 months.

Contraindications of Annona muricata

Oral administration: Internal use may be limited in case of individual intolerance to components, in childhood, during pregnancy and breastfeeding, as well as in conditions requiring control of metabolic load. It is not recommended to take without medical supervision in patients with pronounced metabolic disorders or reduced functional reserve of detoxification systems.

Application to the skin: External use may be contraindicated in case of increased skin sensitivity, in the presence of acute inflammatory reactions or impaired integrity of the skin. In childhood and in persons with high skin reactivity, it is recommended to limit the area of application, duration of use and monitor skin reaction.

Contact with mucous membranes: Forms that involve contact with the vaginal, rectal, nasal, oral, ocular or respiratory mucosa require a preliminary assessment of tolerance. Contraindications may be associated with irritation of the mucous membranes, violation of their integrity, as well as individual hypersensitivity. During pregnancy, lactation and in childhood, the use of these forms requires increased attention and, if necessary, adaptation of the regimen of use.

Instillation into the nose and ears: Use in the form of instillation into the nasal passages or external auditory canal is limited in case of sensitivity, inflammation, mechanical irritation or obstructed outflow. In children, use is possible only at a reduced dosage and with special caution.

Note: In the presence of chronic conditions, reduced general tolerance, as well as when using the drug for the first time, it is necessary to conduct a preliminary assessment of the individual reaction. In case of doubt, a specialist consultation is required. All these contraindications are template and do not replace a clinical decision.

Side Effects of Annona muricata

Oral administration: With internal use, reactions from the digestive system, changes in general well-being, individual sensitivity are possible. Side effects may include subjective discomfort, digestive reactions or short-term changes in mood and sleep. In most cases, the reactions are mild and reversible upon discontinuation of the drug. If persistent or increasing symptoms occur, the intake should be discontinued.

Application to the skin: External use may be accompanied by local reactions, such as burning sensation, redness, itching, dry skin or peeling. In some cases, increased sensitivity of the skin to external stimuli may be observed. With increased dosage, prolonged use or application under a bandage, skin maceration is possible. All reactions are completely reversible after cessation of use.

Contact with mucous membranes: Upon contact of the drug with mucous membranes, irritation, tingling, burning sensation, increased lacrimation, short-term increase in secretion or discharge are possible. Less often — swelling, sensation of a foreign body, reflex cough or sneezing. Side effects are usually reversible and disappear after rinsing the mucous membrane with clean water or stopping use.

Instillation into the nose and ears: Local reactions may occur: increased mucus secretion, tingling, short-term itching or discomfort. With a sensitive mucous membrane — sneezing, tickling or a feeling of congestion are possible. In the ear form — a short-term feeling of pressure or "plug". Symptoms are reversible and do not require special treatment if they resolve on their own.

Note: Side effects, as a rule, are associated with an individual reaction of the body, exceeding the recommended dosage, prolonged continuous use or non-compliance with the route of administration. Before use, it is recommended to conduct a trial use or skin test. All symptoms are reversible with the right tactics. In case of persistent or systemic reactions, it is necessary to stop using the drug and, if necessary, consult a specialist.

Geography of Use and Traditional Medicine of Annona muricata

Soursop is traditionally used in the folk medicine of tropical regions of Central and South America, including the territories of Mexico, Brazil, Colombia, Peru and Ecuador. Its use is widespread in the Caribbean basin, especially in Haiti, Jamaica, Cuba and the Lesser Antilles, as well as in West Africa, Indonesia, India, the Philippines and Thailand. In the cultures of these peoples, soursop is revered as a plant of power capable of "cleansing the body and spirit." In rural areas of Colombia and Peru, the leaves are brewed as a warm infusion, which is taken internally and used externally. In Jamaica, an infusion of the bark is used in purification rituals after funerals. In the folk medicine of the West Indies, fresh fruit juice was considered a cooling agent used in the high heat season. In Nigerian herbal practice, soursop is part of mixtures for steam baths. In Thai traditional village medicine, the leaves are used in compresses and as additives to decoctions for febrile conditions. In ethnographic materials from Central America, the plant is mentioned as an element of ritual cleansing of the dwelling — the leaves are burned on coals to expel the "spirit of disease." The first recorded mentions of soursop as a medicinal plant appear in the chronicles of Spanish missionaries of the 16th century, who described the local healing practices of the Aztecs and Taíno. In the folklore of Afro-Caribbean communities, soursop was also used as an amulet against night fears, tied to the head of a child's bed.

Pharmacodynamics of Annona muricata

Soursop exerts a multi-level pharmacological effect due to the presence of acetogenins, flavonoids and alkaloids. The main effects include antioxidant, anti-inflammatory, spasmolytic and sedative actions. The effect on the nervous system manifests itself in the form of central inhibition associated with modulation of GABA receptors. Immunomodulatory effects are realized through a decrease in the activity of pro-inflammatory cytokines. Extracts exhibit cytotoxic activity at the cellular level, which may be associated with inhibition of mitochondrial enzymes. The systemic level of action is combined with a tissue-specific effect on the liver, mucous membranes and peripheral nervous system.

Pharmacokinetics of Annona muricata

Upon oral administration, the active compounds of soursop, primarily acetogenins, are absorbed in the small intestine. Bioavailability may vary depending on the dosage form: infusions and extracts are absorbed faster, powders — more slowly. Metabolism occurs mainly in the liver with the participation of cytochrome P450 enzyme systems. Distribution of compounds is observed in tissues with a high lipid content, including the brain, which is confirmed by studies revealing neurotropic activity. Excretion is carried out with bile and urine, partially through the intestines. With transdermal and mucosal routes of administration, biological action is limited to the local level with minimal systemic penetration.

Mechanisms of Action and Scientific Rationale of Annona muricata

The main pharmacologically active components of soursop — acetogenins, including annonacin, as well as flavonoids and alkaloids — demonstrate a wide range of mechanisms of action. Acetogenins inhibit complex I of the mitochondrial electron transport chain, leading to disruption of cellular energy metabolism and apoptosis. In addition, they suppress the activity of NF-κB and reduce the expression of pro-inflammatory cytokines. Flavonoid components of soursop affect oxidative stress, stabilizing the activity of antioxidant enzymes (e.g., SOD and GPx). Some studies indicate inhibition of AChE and potentiation of GABAergic activity. Interaction with MAPK and JAK/STAT signaling cascades, as well as a decrease in COX-2 expression, has been shown.

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

Synergy of Annona muricata

Reliable in vitro and in vivo data confirm the synergistic interaction of soursop with turmeric, ginger and black cumin. The complex with curcumin enhances the inhibition of NF-κB and increases the apoptotic activity of acetogenins against tumor cells. In combination with ginger zingiberene, potentiation of antioxidant activity and a decrease in the level of reactive oxygen species are observed. Soursop acetogenins used together with thymoquinone of Nigella sativa exhibit an additive and modulating effect on pro-inflammatory cascades. The proposed point of synergy is the joint inhibition of COX-2 and suppression of the expression of IL-6 and TNF-α cytokines. The general vector of action is systemic, mainly at the level of immune and cellular regulation.

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