Cherimoya (Annona cherimola Mill.)
1. Identity, Botanical Classification, and Common Forms
Botanical and Chemical Identity
Annona cherimola Mill. — also spelled cherimoyer and chirimoya, and called chirimuya by the Quechua people — is a species of edible fruit-bearing plant in the genus Annona, within the family Annonaceae, which also includes the closely related sweetsop and soursop. The Annonaceae family contains about 130 genera and 2,400 species and is one of the oldest families among the flowering plants, with an ancestry of roughly 95 million years.
In the NCBI taxonomy, cherimoya carries Taxonomy ID 49314 and is classified within the lineage: Magnoliidae → Magnoliales → Annonaceae → Annonoideae → Annoneae → Annona. Synonyms in older literature include Annona tripetala Ait. and Annona pubescens. Widely cultivated across tropical and subtropical regions today, A. cherimola originated in upland regions of the Americas; once believed to be native to the Andes of Ecuador and Peru, genetic research now places its origin in Honduras and Guatemala.
It is an evergreen subtropical tree species with genetic evidence indicating a Mesoamerican origin, despite its long association with cultivation in the Andean valleys of Ecuador, Peru, Bolivia, and Colombia at elevations between 700 and 2,400 meters. Main producers of cherimoya today are Spain, Peru, and Chile, with small production areas in California, Israel, and Madeira Island, Portugal.
Morphological Description
The fruit is irregularly heart- or pine cone-shaped, typically 10–20 cm in diameter, featuring thick green skin with overlapping scales that encloses creamy white, custard-like flesh embedded with 15–50 large, glossy black seeds; the edible pulp offers a distinctive sweet flavor reminiscent of a combination of banana, pineapple, papaya, peach, and strawberry. The flesh contains numerous hard, inedible, black, bean-like, glossy seeds, 1–2 cm long and about half as wide.
Common Names and Related Species
Cherimoya is known variously as custard apple, chirimoya, cherimolia, and Hanuman phal. The genus Annona also includes pawpaw (Asimina triloba), sugar apple (Annona squamosa), and the commercially important hybrid atemoya (A. cherimola × A. squamosa). The term "custard apple" is sometimes used loosely to refer to Annona reticulata rather than A. cherimola, and these are distinct species.
Common Forms and Preparations
Fruit pulp is often mixed with wine, milk (to make milkshakes), and yogurt, or processed into ice cream, sherbet, and baked goods such as cookies and pastries. Annona cherimola's main use by the population has been as fresh fruit and in desserts and bakery, but the seeds have been used as medicine and pesticides. In research contexts, plant parts are prepared as ethanolic, methanolic, or aqueous extracts from leaves, seeds, pulp, peel, bark, and roots. Leaf infusions (teas) are employed in traditional medicine in certain Latin American countries.
2. Traditional and Historical Use
Pre-Columbian and Andean Cultures
Cherimoya is a tree cultivated prior to and during the times of the Incas, dating back to 1200 BC in the inner valleys of Peru and Ecuador. Archaeological evidence from Ecuador shows that cherimoya was already known to the Valdivia culture (3500–1600 BC). Pre-Columbian cultures, including the Cupisnique (circa 1000–700 BC) and Moche (circa 200 BC), represented the fruit in phytomorphic ceramics — bottles and vessels modeled after its distinctive scaly form — reflecting its prominence in ancient Peruvian artistry and dietary practices.
The Moche culture of Peru had a fascination with agriculture and represented fruits and vegetables in their art; cherimoyas were often depicted in their ceramics. Cherimoya was a highly valued fruit among the Incas, who referred to it as the "pearl of the Andes."
Traditional Medicinal Uses
Indigenous peoples of the Andes, particularly in Peru and Ecuador, traditionally revered cherimoya for its digestive and restorative properties; the fruit's creamy pulp was commonly consumed to soothe the stomach, alleviate diarrhea, and improve appetite.
Traditionally, A. cherimola extract has been used for various purposes, mostly due to its potent toxic activity. Crushed seeds were used as an insecticide, and for the treatment of lice and parasitic skin infections. Cherimoya seeds and skin have also been used to treat lice or as a remedy for pneumonia and respiratory diseases.
Cherimoya leaves and seeds were employed in folk remedies; infusions or poultices made from the leaves were applied to treat skin irritations and infections, while crushed seeds were sometimes used, with caution, to address parasitic infestations. The dried flowers have been used as flavoring in snuff in Jamaica, while rural Mexicans have sometimes used a dilution of the seeds to induce vomiting or defecation.
Post-Columbian Spread
The Spanish brought the fruit to different parts of the world, especially around the Mediterranean. In Spain, cherimoya has been cultivated for centuries in the Granada province, leading to its recognition as a food of cultural importance. Annona cherimola Miller is a plant used in Mexican traditional medicine for the treatment of diabetes.
3. Key Constituents and Active Compounds
Overview of Phytochemical Classes
Phytochemicals such as flavonoids, tocopherols, tannins, acetogenins, saponins, and polyphenols have been isolated from A. cherimola roots, seeds, pulp, and leaves. In the edible part of cherimoya, compounds such as polyphenols, tocopherols, phytosterols, diterpenes, and triterpenes have been identified. With regard to the phytochemistry of Annona species, the main classes of constituents identified to date are acetogenins, alkaloids, phenols, and essential oils; alkaloids are mainly present in the leaves, whereas acetogenins are present in the seeds and found in smaller quantities in the pulp and leaves.
Annonaceous Acetogenins
Acetogenins represent the most toxicologically significant class of compounds in A. cherimola. Identified acetogenins in cherimoya include cherimolin-2 and almunequin. These plants contain a class of powerful, lipophilic complex I inhibitors — the annonaceous acetogenins. Specialized metabolites of Annona species with anticancer activity include alkaloids, acetogenins, terpenes, flavonoids, coumarins, cyclopeptides, and saponins, with distinct mechanisms of action.
Annonacin — the major acetogenin in the related species A. muricata and present in other Annona species — inhibits complex I in brain homogenates in a concentration-dependent manner and, when administered systemically, enters the brain parenchyma and decreases brain ATP levels by 44%. The acetogenin annonacin has been detected in alcoholic beverages made from A. cherimola pulp, as identified by HPLC-ESI-LTQ-Orbitrap analysis (Le Ven et al., 2014, J. Agric. Food Chem.).
Flavonoids and Polyphenols
The most prominent polyphenols include catechin, proanthocyanidins, and hydroxytyrosol. HPLC-DAD analysis of cherimoya leaf tea infusions revealed that the major flavonoid glycosides are rutin, narcissin, and nicotiflorin. One compound that stands out in the research is poncirin, a flavonoid found in cherimoya that has been shown to reduce oxidative damage by neutralizing free radicals; poncirin also appears to protect nerve cells through anti-inflammatory mechanisms, specifically by blocking a signaling pathway involved in neurological damage. Other identified compounds include rutin and quercetin-related flavonoids, which inhibit the enzyme xanthine oxidase — an enzyme that, when overactive, contributes to oxidative stress and is involved in conditions such as gout.
A comprehensive NMR and HPLC-TOF-MS characterization of cherimoya leaves classified 66 metabolites including sugars, amino acids, phenolic acids and derivatives, flavonoids, phenylpropanoids, and other polar compounds; major compounds identified included sucrose, glucose (α and β), proline, chlorogenic acid, and rutin. Flavonoid derivatives accounted for between 63% and 76% of the total phenolic content in those extracts.
Alkaloids
Alkaloids identified in cherimoya include annocherines, norisocorydine, cheritamine, and annonaine. Phytochemical analyses of cherimoya leaves showed large amounts of phenolic compounds — in particular proanthocyanidins — and identified 18 compounds, either flavonoids or alkaloids; biological activity assessment found antioxidative properties correlated with polyphenols, and antiproliferative activity against HeLa and HepG2 cell lines correlated with alkaloids.
Terpenes and Volatile Compounds
Terpenes in cherimoya include myrcene, pinene, linalool, caryophyllene, terpenolene, and germacrene. In the study of volatile components of Cuban Annona fruits, 47 volatile components were identified in A. cherimola; the major volatiles were α-thujene, α-pinene, terpinen-4-ol, and germacrene D.
Cyclopeptides
Cherimoya also contains cyclopeptides, specifically cherimola cyclopeptide E and cherimola cyclopeptide F.
Macronutrients and Micronutrients
100 g of fresh cherimoya pulp provides about 75 calories and contains no saturated fats or cholesterol; its flesh is a good source of soluble dietary fiber (approximately 3 g per 100 g, or about 8% of the recommended daily amount), which helps decrease the absorption of cholesterol in the gut. Analyzed fruits are a good source of ascorbic acid, with a mean value of 37.66 ± 8.41 mg per 100 g of pulp weight across seven cultivars in one comparative study. One whole cherimoya fruit contains 674 milligrams of potassium and 40 milligrams of magnesium. Cherimoya fruit is also a good source of B-complex vitamins, especially vitamin B-6 (pyridoxine); 100 g fresh fruit provides 0.257 mg, or approximately 20% of recommended daily levels.
The most abundant carotenoid identified in cherimoya is lutein, with values ranging from 129 to 232 µg per 100 g across cultivars.
4. Mechanisms of Action
Antioxidant Mechanisms
Cherimoya is an important source of natural bioactive compounds; in the edible part, polyphenols, tocopherols, phytosterols, diterpenes, and triterpenes have been identified. The polyphenolic fraction — particularly proanthocyanidins and flavonoids — demonstrates free-radical scavenging activity in multiple assays (DPPH, ABTS, FRAP). Polyphenol compounds are the most abundant dietary phytochemicals, and several biological actions are documented, including antioxidant, anti-inflammatory, antidiabetic, antiproliferative, antihypertensive, and antihyperlipidemic effects.
Anticancer Mechanisms (Preclinical)
Several Annona species exhibit anti-parasitic and anti-inflammatory activities; the ethanolic leaf extract of A. cherimola has been evaluated for anti-cancer and anti-proliferative properties on Acute Myeloid Leukemia (AML) cell lines in vitro. Annomolin and acetogenins, isolated from A. cherimola seed extracts, demonstrated a cytotoxic and pro-apoptotic effect in human prostate, breast, and colon cancer cell lines. The principal proposed mechanism is inhibition of mitochondrial respiratory complex I, causing energy depletion in rapidly dividing tumor cells.
Antidiabetic Mechanisms
In vivo and in silico pharmacological studies regarding the use of A. cherimola leaves identified flavonoids rutin and myricetin as sources of potential antidiabetic agents for type 2 diabetes control. During carbohydrate tolerance tests, all treatments reduced the postprandial peak similarly to control drugs; in molecular docking studies, rutin showed affinity in inhibiting α-glucosidase enzymes and myricetin in inhibiting the SGLT1 cotransporter.
Neurotoxic Mechanism of Acetogenins
In vitro and in vivo studies have reported that annonaceous acetogenins, especially annonacin, can damage multiple populations of neurons in the brain — including dopaminergic, cortical, and subcortical neurons — by promoting mitochondrial dysfunction. Annonacin can also induce the redistribution of abnormally phosphorylated tau from neurites to cell bodies in striatal neuronal cultures.
5. Scientific Evidence by Area of Use
5.1 Antioxidant Activity
Evidence level: Established in vitro; no controlled human trials.
The antioxidant activity of pulp, peel, and seeds of four cultivars from A. cherimola from Madeira Island was analyzed; the peel of the Madeira cultivar showed the highest antioxidant capacity (EC50 of 0.97 mg/mL) and total flavonoids (44.7 epicatechin equivalents per 100 g). Total phenolic content in the flesh of seven cultivars varied between 28.50 ± 1.92 (Fino de Jete) and 174.90 ± 11.69 (Chaffey) mg GAE per 100 g of pulp weight, with an average of 75.18 ± 57.94 mg GAE per 100 g.
The cherimoya skin, flesh, and juice were analyzed for antioxidant content using the oxygen radical absorbance capacity (ORAC) assay; the juice showed the highest antioxidant activity, while the flesh exhibited the lowest. All current antioxidant evidence is derived from in vitro laboratory assays; no randomized controlled human trials examining antioxidant endpoints for cherimoya have been published.
5.2 Anticancer Activity
Evidence level: Preliminary; in vitro and animal studies only; no human clinical trials.
A study evaluated the anti-cancer and anti-proliferative properties of A. cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines (Monomac-1 and KG-1) in vitro; the anti-proliferative effect was evaluated via cell viability assay, and the pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining; molecular mechanisms were determined through analysis of apoptotic protein expression via western blots. Treatment with A. cherimola seed ethanolic extract promotes a dose- and time-dependent inhibition of the proliferation of various AML cell lines, but not normal mesenchymal stem cells (MSCs).
Previous studies reported the anti-cancerous effect of A. cherimola ethanolic leaf extract on leukemia; a subsequent study aimed at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines — MDA-MB-231 and MCF-7 — in addition to investigating its toxicity on normal mesenchymal stem cells. All data from that study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.
Separate researchers investigated the antioxidant and anticancer properties on melanoma cells of ethanolic, methanolic, and aqueous Annona cherimola leaf extracts. Of the 166 species of the genus Annona, 29 have been studied for their anticancer activity in their extracts or compounds. All such results are derived from in vitro cell-line studies or animal models. No human clinical trials have been conducted to evaluate cherimoya extracts as anticancer agents.
5.3 Antidiabetic Activity
Evidence level: Preliminary; animal (in vivo) and in silico studies; no human clinical trials.
A 2022 study published in Plants investigated the antidiabetic and toxicological effects of tea infusion extracts from Annona cherimola Miller leaves — a plant used in Mexican traditional medicine for the treatment of diabetes — evaluating tea infusions from 1.5 g of leaf powder collected in May, June, July, and August, on streptozotocin-induced diabetic mice and for subchronic toxicity. Results showed that the tea infusion extract of the August sample exhibited the most significant antihyperglycemic activity; HPLC-DAD analysis revealed that flavonoid glycosides — rutin, narcissin, and nicotiflorin — were the major components, with the August sample containing the highest flavonoid concentration.
A 2025 in vivo and in silico study evaluated the antihyperglycemic activity of aqueous leaf and stem extracts of A. cherimola alone and combined with oral antidiabetic drugs, and assessed their effects on HbA1c percentage, lipid parameters, and toxicity, given that A. cherimola is traditionally used in Mexico to treat diabetes. Nine Annona species including A. cherimola were reviewed in relation to their phytochemical composition and biological activity; polar extracts from these plants induced a reduction in blood sugar levels in chemically induced type-2 diabetic rats, demonstrating the antidiabetic potential of species from this genus. All evidence remains at the preclinical stage; human trials are lacking.
5.4 Anti-inflammatory Activity
Evidence level: Preliminary; in vitro and animal evidence only.
Hepatoprotective, anti-inflammatory, and antitumoral properties have been described for A. cherimola extracts. Catechin and epicatechin, flavonoid antioxidants found in cherimoya, have been found to have powerful anti-inflammatory effects in test-tube and animal studies. No human intervention trials specifically investigating anti-inflammatory outcomes of cherimoya in human subjects have been identified in the peer-reviewed literature.
5.5 Cardiovascular / Antihypertensive Effects
Evidence level: Theoretical / nutritional; no dedicated human trials.
Cherimoya contains nutrients like potassium and magnesium that may help lower blood pressure; eating foods rich in these minerals can help blood vessels relax, which improves blood circulation; one fruit contains 674 milligrams of potassium and 40 milligrams of magnesium. The evidence for cardiovascular benefit is inferred from the general nutritional literature on potassium and magnesium intake rather than from dedicated cherimoya trials.
5.6 Eye Health
Evidence level: Nutritional / observational; no cherimoya-specific trials.
The most abundant carotenoid in cherimoya is lutein, with values ranging from 129 to 232 µg per 100 g. Lutein is found in the eyes, and may help protect against conditions such as age-related macular degeneration (AMD); it also appears to protect against cataracts, and a review of eight studies found that a high level of lutein in the blood was "significantly associated" with a lower risk of getting cataracts. These associations, however, derive from broader lutein literature — not from cherimoya-specific human studies.
5.7 Anticholinesterase / Neuroprotective Activity
Evidence level: Preliminary in vitro only.
Research on the essential oil of Annona cherimola leaves has assessed anticholinesterase activity (relevant to Alzheimer's-type cognitive decline). Antidiabetic and antioxidant reviews of Annona genus species found that seven out of nine studied species reported good antioxidant capacity profiles in different in vitro assays. Neuroprotective potential from flavonoid components (e.g., poncirin) has been proposed based on cell-signaling pathway experiments, but human clinical data are absent.
5.8 Skin and Cosmetic Applications
Evidence level: Patent-stage; limited peer-reviewed human data.
In addition to its organoleptic properties and nutritional value, A. cherimola has a certain potential use in folk medicine, particularly for the treatment of skin disorders. A patent application has described that aqueous seed extracts of Annona cherimola are effective in soothing and calming the human skin; specifically, such extracts enhance the activity of cannabinoid receptor-2 (CB2), inhibit the activity of STAT3, inhibit the expression of IL-1β, IL-8, and calcitonin gene-related peptide (CGRP), and reduce itching and redness and reduce pain perception of irritated skin. These findings are from proprietary research; independent peer-reviewed replication is limited.
6. Body Systems Associated with Cherimoya
- Digestive system: Traditional use for gastrointestinal complaints; dietary fiber content supports gut motility.
- Cardiovascular system: Potassium, magnesium, and vitamin C content implicated in blood pressure regulation and vascular function.
- Immune system: Like other tropical fruits, cherimoya is loaded with vitamin C, a nutrient that supports immunity by fighting infections and disease.
- Neurological system: Acetogenins act as mitochondrial complex I inhibitors; dual relevance to both neurotoxicity (annonacin) and potential anticancer activity.
- Endocrine / metabolic system: Flavonoids studied for antidiabetic potential via α-glucosidase inhibition and SGLT1 cotransporter interaction.
- Ocular system: Lutein content is relevant to retinal and lens health, consistent with the carotenoid's established role in ocular physiology.
- Integumentary system: Traditional topical use of leaf poultices; emerging cosmetic research on seed extracts for skin-calming effects.
7. Dosage Forms and Reported Dosages
No standardized therapeutic dosages for cherimoya extracts have been established by regulatory bodies (NIH ODS, EMA, WHO, ESCOP, or German Commission E). The following dosages have been reported in specific scientific studies only:
- Leaf tea infusion (antidiabetic, mouse study): Tea infusion extracts obtained from 1.5 g of leaf powder were evaluated on streptozotocin-induced diabetic mice and for subchronic toxicity.
- Rat intravenous annonacin study (neurotoxicity): Annonacin, the major acetogenin of A. muricata (closely related), was administered to rats intravenously via osmotic minipumps at 3.8 and 7.6 mg per kg per day for 28 days.
- Cosmetic seed extract: A patent describes a cosmetic skin care composition in which seed extract is present in an amount of 0.05 to 25.0% (w/w).
- Phenolic content (cultivar study): Total phenolic content in cherimoya flesh varied between 28.50 and 174.90 mg GAE per 100 g of pulp weight, depending on cultivar.
Although reliable, double-blind, placebo-controlled research on the medicinal uses of cherimoya is still lacking, the plant has been used for various purposes as part of traditional practices, mostly limited to its native regions.
8. Safety Considerations
Seed Toxicity
Cherimoya seeds are poisonous if crushed open. Contact of A. cherimola seed extract with the eyes has incidentally caused blindness, and ingestion of the extract caused gastrointestinal disturbances such as nausea, vomiting, flatulence, and atropine-like effects including photophobia and dryness of the mouth. Important toxic components of the seeds include the annonaceous acetogenins (ACGs).
Whole Plant Neurotoxins
Like other members of the family Annonaceae, the entire plant contains small amounts of neurotoxic acetogenins, such as annonacin, which appear to be linked to atypical parkinsonism in Guadeloupe. Acetogenins could be involved in the pathogenesis of certain neurodegenerative disorders, such as the high prevalence of atypical parkinsonism that occurs in Guadeloupe, in some parts of the Afro-Caribbean region, and among the Indian population residing in London and New Caledonia; this could be partially explained by the high consumption of dietary supplements and fruit products containing plant material from Annonaceae.
There is an unexpectedly high proportion of atypical forms of degenerative parkinsonism in the French Caribbean islands; residents of these islands are thought to be susceptible to Caribbean atypical parkinsonism (CAP) owing to their consumption of Annonaceae plant products containing the mitochondrial toxin annonacin. Experimental and epidemiological evidence suggests that the consumption of Annonaceae plant products could worsen disease severity and cognitive deficits in patients with CAP and Parkinson's disease.
Injection of acetogenins in mice increased the proportion of polychromatic erythrocytes, indicating the acetogenins' in vivo genotoxic capacity.
Bark Extract
An extract of the bark can induce paralysis if injected. This property is relevant to parenteral or highly concentrated preparations and does not apply to normal dietary consumption of the fruit pulp.
Edible Pulp vs. Non-Edible Parts
Only the pulp of cherimoya should be eaten; the skin and the seeds, which should not be crushed, should be discarded. Acetogenin concentrations are highest in seeds and bark, and substantially lower in the edible fruit pulp. The risk from occasional consumption of the ripe fruit pulp is generally considered low in the context of a varied diet, but the risk from concentrated extracts, high-frequency consumption, or consumption of non-pulp plant parts is not negligible given the established epidemiological association with atypical parkinsonism.
Anticancer Potential vs. Neurotoxic Risk — a Dual Profile
It has been proven that annonacin is selective to tumor cells, with over 87% of cell survival when the acetogenin is applied to non-tumoral liver cells (HEK-293). However, this selectivity has only been demonstrated in in vitro systems; the neurotoxic effects observed in animal models and epidemiological studies represent a significant safety concern that would need to be resolved before any therapeutic use of acetogenin-containing extracts in humans could be established.
Absence of Formal Drug Interaction Data
No formal pharmacokinetic drug interaction studies for cherimoya or its isolates in humans have been published in the peer-reviewed literature as of the time of this writing. Given the inhibitory effects of acetogenins on mitochondrial complex I, interactions with other mitochondria-affecting agents (e.g., metformin) are a theoretical concern that has not been studied in humans.
References
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