Soursop (Annona muricata L.): A Comprehensive Reference
1. Identity and Botanical Description
1.1 Nomenclature and Taxonomy
Annona muricata Lin., commonly called soursop, is part of the Annonaceae family, which comprises more than 130 genera and 2,300 species. Also known as soursop, graviola, and guanabana, it is an evergreen plant mostly distributed in tropical and subtropical regions of the world. In Spanish-speaking regions the fruit is frequently called guanábana, in Brazil graviola, in Southeast Asia sirsak (Indonesian) or durian belanda (Malaysian), and in the French Antilles corossol. It is also recognized by many other indigenous names, including annone, anona, araticum grande, araticum-manso, coronsol, corossol épineux, grand corossol, cachiman épineux, mkononono, saput, sauersack, stachelannone, taggannona, and zuurzak.
1.2 Physical Characteristics
Annona muricata (Annonaceae), commonly called soursop due to the soured and acidic nature of the matured and ripe fruit pulp, is a small, upright evergreen tree growing 5–10 metres in height. It is easily recognisable by its prickly, heart-shaped green fruit, which can reach up to 12 inches in length. The leaves are obovate, oblate, and acuminate in shape, with a dark green, thick, and glossy upper surface. The fruits are dark green and prickly, and the flower petals are thick and yellowish. This plant is widely grown in tropical and subtropical areas, such as Southeast Asia, South America, and the rainforests of Africa.
1.3 Common Forms and Preparations
The fruits of A. muricata are extensively used to prepare syrups, candies, beverages, ice creams, and shakes. All parts of A. muricata are used in traditional medicine by people who live in tropical areas, with the leaves, stem bark, roots, and seeds primarily used as medicinal ingredients. As a dietary supplement, the plant is commercially available in multiple forms, including encapsulated leaf powder, standardised leaf extracts (aqueous and ethanolic), liquid tinctures, and loose-leaf teas for infusion. The plant produces edible fruit all year round and is widely used as a traditional medicine for skin disease, respiratory disease, and fever.
2. Traditional and Historical Use
2.1 Origins in the Americas
Soursop originates from tropical regions of the Americas, and its cultivation dates to precolonial times, when indigenous populations held it in high regard for its tangy flavour and therapeutic properties. The origins of soursop trace back particularly to the Caribbean and Central America, where indigenous peoples were among the first to cultivate and utilise it for its culinary and wellness properties. The leaves and bark of the soursop tree were also employed in traditional medicine, believed to treat ailments such as fever, pain, and infections, laying the foundation for soursop's enduring cultural significance.
2.2 Colonial-Era Spread
The arrival of European explorers in the Americas during the late 15th and early 16th centuries marked a turning point in the history of soursop. European explorers and colonisers encountered the fruit and began to document its uses and benefits, introducing soursop to other tropical regions through the extensive trade routes of the colonial era. By the 17th century, soursop had found its way to tropical regions of Asia and Africa, where it quickly adapted to the new environments.
2.3 Traditional Medicinal Uses by Region
A wide array of ethnomedicinal activities is attributed to different parts of A. muricata, and indigenous communities in Africa and South America extensively use this plant in their folk medicine. A. muricata leaves are used to treat headaches, insomnia, cystitis, and cancer; the seeds are used to treat parasitic infections; and the fruit is used to treat diarrhoea and neuralgia, eliminate worms and parasites, increase milk production in lactating women, and reduce fever.
In several tropical sub-Saharan countries such as Uganda, all parts of the plant are used to treat malaria, stomach ache, parasitic infections, diabetes, and cancer. Additionally, the seeds are used as anthelmintic and antiparasitic treatments, and the leaves, bark, and roots of A. muricata have been used for their anti-inflammatory, antihypertensive, sedative, antidiabetic, smooth muscle relaxant, and antispasmodic effects.
It is a shrubby plant located majorly in the rain forest regions of Nigeria, where it is used locally for several ethnomedicinal purposes—as a laxative and purgative, and for wound healing. In the Amazon basin, the plant is known as graviola; indigenous tribes have a deep-rooted relationship with the plant, viewing the leaves as a vital tool for internal cleansing, and in the mountainous regions of Peru, Graviola leaves have a long history as a traditional remedy for intestinal distress, with tribes brewing a bitter decoction of dried leaves to treat parasites and catarrh (inflammation of the mucous membranes).
The leaves and stems are also used in traditional medicine for symptoms associated with inflammation and infection. In some Caribbean countries, soursop/graviola is one of the common herbal remedies used among prostate, breast, and colorectal cancer patients.
3. Key Constituents and Active Compounds
3.1 Major Phytochemical Classes
The major compounds in A. muricata are acetogenins, alkaloids, flavonoids, essential oils, vitamins, carotenoids, amides, and cyclopeptides. Additionally, the plant contains minerals such as K, Ca, Na, Cu, and Fe. Among the secondary metabolites of A. muricata, acetogenins constitute approximately 49%, alkaloids 26%, flavonoids 19%, and others 6%, which are reported to be responsible for the plant's pharmacological activities.
The phytochemicals present in Annona muricata include alkaloids, flavonoids, carbohydrates, cardiac glycosides, saponins, tannins, phytosterols, terpenoids, and proteins.
3.2 Annonaceous Acetogenins
Phytochemical studies reveal that annonaceous acetogenins are the major constituents of A. muricata. More than 100 annonaceous acetogenins have been isolated from leaves, barks, seeds, roots, and fruits of A. muricata. These molecules are structurally distinct from most other plant compounds because they are derivatives of very long-chain fatty acids, typically containing 32 to 37 carbon atoms. The structure of an acetogenin resembles a long, waxy hydrocarbon chain with a specialised polar head and ring systems.
Key named acetogenins isolated from A. muricata include annonacin, annomuricins A and B, annopentocin, annohexocin, bullatacin, squamocin, and muricatacin. Annonacin was the most abundant acetogenin reported in both leaves and fruit of A. muricata, but has also been reported in seeds, peel, and roots.
3.3 Alkaloids
The alkaloids identified in A. muricata include coreximine and reticuline. Additional alkaloids found in the plant include nornuciferine, xylopine, atherosperminine, asimilobine, and s-norcorydine, as identified by phytochemical screening. Rutin, xi-anomuricine, kaempferol-3-O-rutinoside, nornuciferine, xylopine, atherosperminine, caffeic acid, asimilobine, s-norcorydine, loliolide, annohexocin, annomuricin, annopentocin, and sucrose have been identified as extract bioactive components.
3.4 Flavonoids and Phenolic Compounds
The phenolic compounds in A. muricata, such as quercetin and gallic acid, are reported to be the compounds most responsible for the antioxidant capacity of the plant. Rutin has been identified as the predominant phenolic compound in ethanolic leaf extracts. The acidified ethanolic extract showed the highest phenolic content, with rutin as the predominant compound. Other polyphenols identified in various plant parts include kaempferol and caffeic acid. Flavonoids such as quercetin and kaempferol have been studied for their antioxidant capabilities, which can help in reducing oxidative stress.
3.5 Nutritional Composition of the Fruit
Soursop fruit is sweet with an exotic flavour and loaded with essential vitamins, minerals, and antioxidant-rich polyphenolic compounds. Soursop (Annona muricata) exhibits significant nutritional properties, being rich in protein, lipids, fibre, and minerals. Proximate composition of the pulp and juice has been reported to include protein (0.58–7.45%), lipid (0.10–0.74%), fibre (1.26–24.23%), ash (1.29–2.22%), carbohydrate (8.63–21.0%), and moisture (45.0–88.23%). Soursop also contains vitamins C and B, potassium, iron, folate, zinc, and magnesium.
4. Mechanisms of Action
4.1 Mitochondrial Complex I Inhibition
Acetogenins are powerful cytotoxic agents that bind to and potently inhibit ubiquinone oxidoreductase in mitochondrial complex I (a membrane-bound protein component of the mitochondrial electron transport system) and ubiquinone-linked NADH oxidase in the plasma membranes. Acetogenins bind tightly within the ubiquinone-binding channel of Complex I, blocking the transfer of electrons, which effectively shuts down the entire electron transport chain.
Annonacin displays its toxic effects on the cell by the suppression of mitochondrial complex I, which results in ATP depletion, and the repression of ubiquinone-linked NADH oxidase that is vital for expression in cancer cell membranes, which kills the cancer cell and arrests the proliferation of cells.
4.2 Apoptosis Induction in Cancer Cells
These acetogenins preferentially destroy cancer cells through the action as a DNA topoisomerase I toxin, prevent cancer cells from entering their G1 phase, activate pathways linked to Bax and caspase-3, and block NADH-ubiquinone oxidoreductase (complex I) in mitochondria. In vivo studies demonstrated tumour growth inhibition exceeding 60% in xenograft models using acetogenin-rich fractions; these findings are supported by mechanistic studies showing induction of apoptosis via caspase-3 activation and cell cycle arrest at G1 phase.
4.3 Antidiabetic Mechanisms
The inhibitory effects of soursop fruit parts on key enzymes linked to type-2 diabetes (α-amylase and α-glucosidase) and hypertension [angiotensin-I converting enzyme (ACE)] have been investigated. The data revealed that aqueous extracts of soursop fruit parts inhibited α-amylase, α-glucosidase, and ACE activities in a dose-dependent manner; the pericarp extract had the highest α-amylase (EC50 = 0.46 mg/mL), α-glucosidase (EC50 = 0.37 mg/mL), and ACE (EC50 = 0.03 mg/mL) inhibitory activities.
In vitro studies found that pulp- and leaf-based extracts of soursop exhibited greater enzymatic inhibition than acarbose and greater alpha-glucosidase inhibition than alpha-amylase; an in silico study reported that the enzymatic inhibition of soursop is not competitive and pointed to acetogenins as a main active component.
4.4 Antihypertensive Mechanisms
Studies suggest the potential ameliorative effects of Annona muricata leaf extracts against hypertension in animal models; notably, studies have shown the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, reflected in their ability to attenuate oxidative stress and inflammatory cytokines in hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.
4.5 Antioxidant Activity
Perceived health benefits of graviola are in part attributed to its antioxidant properties. Soursop extracts can scavenge radicals, reduce Fe³⁺ to Fe²⁺, and chelate Fe²⁺. Fruit extracts have been found effective in scavenging DPPH radicals (78.6%) at a concentration of 250 µl/mL, as well as inhibiting lipid peroxidation (16.2%).
5. Scientific Evidence by Health Area
5.1 Anticancer Activity
Nature of evidence: Predominantly in vitro and animal studies; human clinical evidence is extremely limited and preliminary.
In vitro investigations have shown that Annona muricata extracts exhibit remarkable cytotoxicity against various cancer cell lines. Research has revealed potent activity against pancreatic cancer cells (PANC-1, IC50 = 4.6 µg/mL) through mitochondrial disruption. A study using leaf methanol extract (LMAM) exhibited significant inhibition of MCF-7 breast cancer cells with an IC50 value of 85.55 µg/mL; Hoechst staining showed morphological features characteristic of apoptosis in LMAM-treated cells, and cell cycle analysis confirmed a 30% rise in the G1 phase upon treatment with 100 µg/mL LMAM, thus inducing cell cycle arrest.
Among the numerous phytochemicals in A. muricata, acetogenins and flavonoids have demonstrated outstanding cytotoxic properties on several in vivo and in vitro cancer models. Acetogenins from A. muricata exhibited potent anticancer effects (IC50 = 14.69 µM) on multidrug-resistant breast tumours via alteration of mitogen-activated protein kinase (MAPK) signalling and induction of apoptosis in MCF-7/ADR cells via the mitochondrial pathway.
At the clinical level, evidence is extremely scarce. A study that administered 300 mg of A. muricata leaf water extract to patients with colorectal cancer in capsule form after breakfast reported inhibition of colorectal cancer cell growth (DLD-1 and COLO 205); the A. muricata leaf water extract was reported to have selective inhibitory activity against colorectal cancer cells and not inhibit normal cell growth. The inhibition was modulated by acetogenin activity in the complex I mitochondrial electron transport chain, hampering ATP formation needed for cancer cell growth. Consumption of 5 g of leaf extract powder and seeds of A. muricata three times per day accompanied by lifestyle modifications was shown to help the healing process in patients with colon cancer in a separately reported study.
Graviola/soursop is also widely promoted as an alternative treatment for cancer, although clinical evidence is lacking. Research has identified the need for clinical research to explore mechanisms of action, effective and tolerable dose, and any adverse effects, including potential drug interactions with Annona muricata, to inform its use in the management of cancer, either alone or as part of an integrated treatment approach. It must be emphasised that most of these studies have been concerned with the in vitro anti-cancer evaluation of isolates on various cancer cell lines.
5.2 Antidiabetic Effects
Nature of evidence: In vitro enzyme inhibition assays and animal models; no robust human clinical trials identified.
In animal models, graviola extracts showed antidiabetic effects. An aqueous A. muricata leaf extract given for 24 weeks to obese mice led to significant weight loss compared with both the normal control (P=0.003) and obese untreated controls (P=0.034), particularly with a 100 mg/kg extract dose. Intestinal glucose absorption was decreased (P<0.05) while muscle tissue glucose absorption was increased; significant improvements in basal insulin levels (P<0.001) and overall insulin levels (P<0.05) in a diabetic model were also demonstrated with the extract compared with controls.
In vitro, the phenolic contents in soursop fruit part extracts ranged from 85.65 to 560.21 mg/100 g, with the pericarp showing the greatest enzyme-inhibitory activity. These in vitro results require further validation in human clinical settings, which have not been adequately performed to date.
5.3 Antihypertensive Effects
Nature of evidence: In vitro ACE inhibition and rat models; no identified human clinical trials.
The Annona muricata leaf extract (AMLE) significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure in rat models of L-NAME-induced hypertension. In a murine model, graviola also showed hypotensive effects, and may have additive effects with antihypertensive drugs. The clinical relevance of these findings for human hypertension management has not been established.
5.4 Antiparasitic and Antimalarial Activity
Nature of evidence: In vitro, in vivo (animal), and limited in silico studies; no adequate human trials identified.
Among 49 research articles reviewed from 1981 to 2021, A. muricata's activities were shown to include antiprotozoal activity (10% of studies reviewed). Numerous investigations have substantiated antiparasitic, antimalarial, and anticonvulsant activities among others in A. muricata. These studies have predominantly been conducted in animal or laboratory settings.
5.5 Antiulcer Activity
Nature of evidence: Animal and in vitro studies only.
In animal models, graviola extracts showed antiulcer effects. In the comprehensive review of 49 published studies, antiulcer activity constituted the second most common pharmacological finding (17% of studies), though all of the reviewed evidence was preclinical.
5.6 Antimicrobial and Antifungal Activity
Nature of evidence: In vitro studies only; no human trials.
Research demonstrated a significant inhibitory effect of A. muricata extract, with the ability to reduce fungal growth by 58% and cell density by 65% in Candida albicans; the extract affected both the fungal plasma membrane and cell wall integrity, with significant reduction in cell viability. These findings show that the A. muricata extract is a source of chemical diversity, which acts as a potential antifungal agent with promising application to the therapy of infections caused by C. albicans.
5.7 Antiviral Activity
Nature of evidence: In vitro and laboratory surrogate models; no human trials.
A. muricata extracts have shown effectiveness against viruses because they can decrease viral replication. Studies characterising both aqueous and ethanolic leaf extracts have evaluated antiviral effects using bacteriophage surrogates, but to date no evidence of the antiviral capacity of soursop leaves specifically on enteroviruses has been reported.
5.8 Wound Healing
Nature of evidence: Animal (in vivo) studies only.
Two doses of A. muricata ethyl acetate extract showed significant wound healing activity in both macroscopic and microscopic analyses of wounds; wound treatment with an ointment containing A. muricata ethyl acetate extract caused a significant increase in antioxidant levels and a decrease in MDA level in wound tissues compared with those in the vehicle control. A. muricata bark and leaf extracts also showed wound healing effects compared with untreated wounds.
5.9 Neurological and Cognitive Effects
Nature of evidence: Animal studies; no human trials. Note: evidence cuts both ways — potential cognitive benefit but also well-documented neurotoxic risk (see Section 7).
Cognitive impairment caused by scopolamine was improved by A. muricata extracts at 50 and 100 mg/kg in animal studies, suggesting that the extracts at those dosages can improve cognitive function in the experimental model. However, this must be contextualised against the substantial body of evidence documenting the neurotoxic potential of annonacin (discussed below).
6. Body Systems and Health Areas of Association
- Oncology: Predominantly in vitro cytotoxic and pro-apoptotic activity across multiple cancer cell lines; preliminary and methodologically weak clinical data.
- Metabolic / Endocrine: In vitro and animal evidence for inhibition of carbohydrate-metabolising enzymes (α-amylase, α-glucosidase) relevant to blood glucose regulation.
- Cardiovascular: In vitro ACE inhibition and animal model evidence for blood pressure reduction and lipid profile improvement.
- Gastrointestinal: Traditional and animal-study evidence for antiulcer, antidiarrhoeal, and antiparasitic effects.
- Infectious Disease: In vitro evidence for antibacterial, antifungal, antiviral, and antiprotozoal/antimalarial properties.
- Integumentary: Animal model evidence for wound healing acceleration.
- Neurological: Animal model evidence for cognitive modulation; offset by documented neurotoxic risk in epidemiological and animal data.
- Antioxidant / Immunomodulatory: Established free radical scavenging and anti-inflammatory activities across multiple in vitro and animal studies.
7. Dosage Forms and Doses Reported in Studies
Soursop/graviola is available commercially as whole dried leaf, encapsulated leaf powder, standardised extracts (aqueous, ethanolic, or methanolic), liquid tinctures, and fruit juices. The following dosage levels have been reported in published studies — not as recommendations, but as a factual record of what has been tested:
- 300 mg of A. muricata leaf water extract in capsule form, administered after breakfast, was reported in a study of colorectal cancer patients.
- Consumption of 5 g of leaf extract powder and seeds three times per day accompanied by lifestyle modifications was reported in a study examining colon cancer healing.
- A 100 mg/kg dose of aqueous A. muricata leaf extract was administered for 24 weeks to obese mice in a weight-loss and metabolic study.
- Doses of 50 and 100 mg/kg of methanol extract were used in a mouse model of scopolamine-induced cognitive impairment.
- In cytotoxic in vitro studies, concentrations ranging from 25–250 µg/mL were assessed against MCF-7 breast cancer cells, with treatment concentrations of 50 and 100 µg/mL used in follow-up mechanistic assays.
No standardised, evidence-based dosing regimen for any indication has been established in human clinical trials.
8. Safety Considerations and Drug Interactions
8.1 Neurotoxicity and Atypical Parkinsonism — The Primary Safety Concern
The most extensively documented and clinically significant safety concern with soursop is neurotoxicity attributable to annonacin and related acetogenins. The most serious safety concern with graviola involves the same acetogenins that make it biologically interesting; annonacin, the most abundant acetogenin in graviola, is fat-soluble enough to cross the blood-brain barrier, and once there, it can damage neurons by disrupting their energy production.
Annonacin has been linked to the abnormally high incidence of progressive supranuclear palsy and atypical Parkinsonism in the Caribbean island of Guadeloupe, where consumption of fruits such as the soursop (Annona muricata) is common. Of 87 people with Parkinsonism transferred to one clinic between 1996 and 1998, 25% had Parkinson's disease, while 36% had progressive supranuclear palsy and 39% had atypical Parkinsonism.
Overconsumption of graviola fruit and products made from it has been linked to an atypical form of Parkinson's disease that does not respond to the standard treatment (l-DOPA). More recently, it was shown that chronic consumption of graviola juice can trigger and aggravate the phosphorylation of cerebral tau protein, leading to tau pathologies, including Parkinson's disease.
This class of polyketides (acetogenins) are among the most potent inhibitors of complex I of the mitochondrial respiratory chain known in nature, some 50-fold more potent than the class complex I inhibitor MPP⁺ and two times more potent than rotenone in inducing neuronal death.
In rat studies, 28 days of annonacin exposure caused a 32% loss of dopamine-producing neurons in a brain region critical for movement, along with significant damage to other neuron types; the pattern of brain damage closely resembled what is seen in patients with Parkinson's disease.
There is more annonacin in graviola fruit (768 µg/g dry weight) than in the leaves (306 µg/g dry weight). A tea made from 2.5 g of graviola leaves added to 237 ml (one cup) of water at 90°C for 10 minutes had only 0.213% of the annonacin that was present in the entire leaves. Despite this attenuation via infusion, if a tea made from graviola leaves can cause damage to the brain and liver of rats, the fruits and seeds of this and other plants in the Annonaceae family probably can too, but at much lower doses; similarly, the entire leaves that are sold as dietary supplements could be toxic.
The evidenced neurotoxic mechanisms were via the inhibition of neuronal mitochondrial complex I and dysfunctions of the tau protein. Acetogenins demonstrated punctual and selective anti-cancer action, though their selectivity remains unclear, and effects associated with neurodegeneration have been identified. The evidence of neurotoxicity and cytotoxicity converges in a selectivity relationship associated with cells that require high energy demand, which seems to be a key feature for understanding these synergistic effects.
8.2 Hepatotoxicity
It has been shown by epidemiological studies in human populations (such as those from the Caribbean island of Guadeloupe and those from New Caledonia) with high and prolonged intakes of soursop fruit pulp that annonacin is associated with the occurrence of a neurodegenerative disease known as atypical parkinsonism. This finding, together with the known effects of the acetogenins on mitochondrial toxicity, makes the consumption of soursop, its concentrates, and derivatives without purification a matter of concern. Animal studies have also noted cytoplasmic vacuolisation and eosinophilic hepatocyte changes in the livers of rats given soursop leaf preparations.
8.3 Potential Drug Interactions
In a murine model, graviola showed hypoglycaemic effects and may have additive effects with antidiabetic drugs; clinical relevance is not known. In a murine model, graviola also showed hypotensive effects and may have additive effects with antihypertensive drugs.
Scientific studies evaluating the potential enhancing or additive effects of Annona muricata with conventional antineoplastic drugs remain limited; one study aimed to assess the cytotoxic effects of an aqueous AM infusion alone and in combination with standard antineoplastic drugs in cancer cell lines, while also evaluating its safety in healthy cells. In human leukocytes, treatment with AM infusion alone at concentrations of 125 and 250 µg/mL resulted in a noticeable decrease in cell viability; when combined with antineoplastic drugs, the infusion further amplified cytotoxic effects. This finding raises questions about the safety of concurrent use of soursop preparations and conventional chemotherapy, but has not been evaluated in human clinical trials.
8.4 Caution in Specific Populations
Chronic exposure to acetogenins can potentiate neural damage; thus, moderate consumption of infusions, extracts, and pulp of Annonaceae fruits is recommended based on the existing evidence. The whole fruit provides real nutrients, particularly fibre, vitamin C, and potassium, without the concentrated doses of acetogenins found in leaf-based supplements; supplement forms carry more uncertainty, both in terms of potential benefits and the neurotoxicity risk that comes with higher, more frequent exposure to annonacin.
Use of annonacin-containing products in Guadeloupe often lasts from early childhood through old age, and daily consumption is not uncommon; it was discovered that atypical Parkinsonism was predominant in elderly males who regularly consume annonacin-containing herbal teas. The cumulative pattern of exposure is therefore a critical variable in risk assessment.
9. Overall Evidence Assessment
From 49 research articles obtained from 1981 to 2021, A. muricata's activities were shown to include anticancer (25%), antiulcer (17%), antidiabetic (14%), antiprotozoal (10%), antidiarrhoea (8%), antibacterial (8%), antiviral (8%), antihypertensive (6%), and wound healing (4%). The breadth of these activities is well-documented in preclinical research. However, the overwhelming majority of evidence for therapeutic benefit derives from in vitro cell-based assays and animal models. The translation of these findings to established clinical efficacy in humans has not occurred for any indication. The single most important and well-substantiated finding concerning soursop in humans is not a benefit but a risk: the association between regular and high-volume consumption of soursop products and atypical parkinsonism, documented epidemiologically in Guadeloupe and New Caledonia and mechanistically explained by annonacin's potent Complex I inhibition in dopaminergic neurons.
References
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