Gen info
- Annona or Annona is a genus of flowering plants in the pawpaw/sugar apple family, Annonaceae. It is the second largest genus in the family after Guatteria, containing about 166 species.
- Etymology: The genus name Annona derives from anón, a Hispaniolan Taino word for the fruit.

Botany
• Anonas is a tree growing to a height of 10 meters or less. Leaves are shiny, oblong to oblong-lanceolate, up to 20 centimeters long, 2 to 5 centimeters wide, pointed at the tips, with petioles 1 to 1.5 centimeters long. Flowers are greenish-yellow, fragrant, 2 to 2.5 centimeters long, occurring in two or three together on lateral peduncles. Outer petals appear as in atis; the inner one is very small, narrowly oblong, or wanting. Fruit is large, heart-shaped, brownish-yellow, about 8 centimeters or more in diameter, with pentagonal areoles outside. Skin is thin, covering a cream-colored, fair-flavored, juicy, and sweet pulp.

• Annona reticulata is a small deciduous or semi-evergreen tree reaching 8 metres (26 ft) to 10 metres (33 ft) tall with an open, irregular crown. Slender leaves are hairless, straight and pointed at the apex (in some varieties wrinkled), 10 centimetres (3.9 in) to 20 centimetres (7.9 in) long and 2 centimetres (0.79 in) to 7 centimetres (2.8 in) wide. Yellow-green flowers are generally in clusters of three or four 2 centimetres (0.79 in) to 3 centimetres (1.2 in) diameter, with three long outer petals and three very small inner ones. Its pollen is shed as permanent tetrads. Fruits vary in shape, heart-shaped, spherical, oblong or irregular, varying in size from 7 centimetres (2.8 in) to 12 centimetres (4.7 in), depending on the cultivar. When ripe, the fruit is brown or yellowish, with red highlights and a varying degree of reticulation, depending again on the variety. Flesh varies from juicy and very aromatic to hard with a repulsive taste. 

Distribution
- Naturalized.
- Cultivated throughout the Philippines.
- Introduced from tropical America by the Spaniards.
- Native to Belize, Colombia, Costa Rica, El Salvador, Guatemala, Honduras, Mexico Central, Mexico Gulf, Mexico Northeast, Mexico Northwest, Mexico Southeast, Mexico Southwest, Nicaragua, Panamá, Venezuela.
- Now pantropic in cultivation.

Constituents
- Study of the bark obtained a crystalline alkaloid from the bark, C17H17NO3, named anonaine (0.03%).
- Another bark study identified the same alkaloid as belonging to the aporphine type, establishing it as 5-6 dioxymethylene-aporphine.
- The bark and seeds are high in tannic acid.
- Fruits yield 6.2% dextrose and 4.22% levulose.
- Study of seeds yielded thirteen compounds, eight annonaceous acetogenins (polyketides) annonareticin (1), 2, 4-cis-isoannonareticin (2-1), 2, 4-trans-isoannonareticin (2-2), solamin (3), murisolin (4), reticulacinone (5), annoreticuin (6), annomonicin (7), together with five other compounds identified as beta-sitosterol (8), daucosterol (9), sucrose (10), palmitic acid and stearic acid (12). 2, 4-cis-isoannonareticin (2-1) is a new annonaceous acetogenin. (29)
- Leaf extracts yielded steroids, terpenoids, tannin, saponin, phenols, alkaloids, and flavonoids. (31)
- Study of leaves yielded nine compounds: annonaretin A, a new triterpenoid (1), annonaretin A (1), kaurenoic acid (2), taraxerol (3), β-sitosterol (4), 16α-hydro-19-al-ent-kauran-17-oic acid (5), 6β-hydroxystigmast-4-en-3-one (6), and 17-acetoxy-16β-ent-kauran-19-oic acid 24 (7); purification of the ethyl acetate soluble afforded 16α-hydro-ent-kauran-17,19-dioic acid (8), and (2S)-di-O-methylquiritigenin (9). (see study below) (16)
- Leaf extract yielded nine compounds, viz., 1,2-Di(8-hydroxy-2-methyl quinolin-7-yl)ethane (1), trans- sesquilavandulyl acetate (2), decanoic acid, Methyl ester(CAS) (3), (Z,Z)-2,12-tetradecadiene (4), pentadecanoic acid, methyl ester(CAS) (5), 1-hydroxyoctan-4-one (6), diallyl 2-diazosuccinate (7), 5-ethyl-pyrogallol (8), (RS)-3-methyl-4(2-oxo-2-phenyl ethyl) cyclopent-2-en-1-one (9). (see study below)   (14)
- Nutritive value per 100 g of custard apple yielded: (Principle) energy 101 Kcal, carbohydrates 25.20g, protein 1.70 g, total fat 0.60 g, cholesterol 0 mg, dietary fiber 2.4g; (Vitamins) niacin 0.500 mg, pantothenic acid 0.135 mg, pyridoxine 0.221 mg, riboflavin 0.100 mg, thiamin 0.80 mg, vitamin A 33 IU, vitamin C 19.2 mg; (Electrolytes) sodium 3 mg, potassium 382 mg; (Minerals) calcium 30 mg, iron 0.71 mg, magnesium 18 mg, manganese 0,093 mg. phosphorus 21 mg. (Phyto-nutrients) epitachin 5.6 mg, proanthocyanidin monomers 6.2 mg, proanthocyanidin dimers 24.3 mg.
- Phytochemical screening of fruit rind and pericarp yielded carbohydrates, terpenoids, proteins, steroids, tannins, and phenols, with absence of alkaloids, flavonoids, saponins, and starch. Seeds yielded alkaloids, carbohydrates, terpenoids, proteins, steroids, and phenols, with absence of flavonoids, saponins, tannins, and starch. (46)
- Study for volatile oils yielded main compounds of camphene (0.2-6.6%), α-copaene (2.0-7.3%), ß-elemene (5.9-16.6%), ß-caryophyllene (8.3-14.9%), ß-bisabolene (0.4-10.2%), δ -cadinene (1.7-4.8%), and germacrene D (9.3-22.8%). (47)
- Qualitative phytochemical screening of A. reticulata leaf (L), bark (B), and seed (S) yielded starch. proteins, tannins, alkaloids, flavonoids, glycosides, and carbohydrates in leaves, bark, and seed; and saponins only in leaves.

Properties
- The fresh leaves are anthelmintic internally and suppurant and insecticidal externally.
- The bark is astringent and tonic.
- Studies have shown anthelmintic, anticancer, antioxidant, hepatoprotective, antibacterial, antiproliferative, analgesic, anti-inflammatory, insecticidal, antihyperglycemic, CNS depressant, larvicidal properties.

Parts used
Leaves, fruit, leaves, bark.

Uses
Edibility
- Fruit is edible but is not so prized in the Philippines as atis or guayabano.
Folkloric
- In the Philippines, leaves used as topicals and applied to the stomach of children suffering from indigestion: The leaves are warmed in open fire and applied to the stomach while still warm, kept in place by an abdominal binder, and renewed every 2 hours. Also used for babies.
- The powdered bark used for dysentery and diarrhea.
- Fresh leaves used as anthelmintic; externally used as suppurant.
- Fruit is anthelmintic; the dried unripe fruit is astringent and used for diarrhea and as vermifuge.
- The unripe fruit is dried, pulverized and used for diarrhea and dysentery.
- The roots used for epilepsy.
- Crushed leaves or paste of the fruit used as poultice for boils, abscesses and ulcers.
- Decoction of the bark is astringent and taken as tonic.
- Bark in powdered form used for diarrhea and dysentery.
- In severe diarrheal cases, a potent decoction is made from the leaves, bark and green fruits, boiled together for five minutes in a liter of water.
- Fragments of root bark are packed around the gums to relieve toothache.
- Root decoction as febrifuge.
- Used traditionally for treatment of epilepsy, dysentery, heart problems, parasite and worm infestations, constipation, hemorrhage, fever, ulcers, and as insecticide. Bark used as astringent and tonic.
- In Bangladesh, used for treatment of epilepsy, toothaches, tumors, fever, and dysentery. (42)
- In the West Indies, fruit is used as anthelmintic; the unripe and dried fruit used as astringent and vermifuge, and for diarrhea and dysentery.
- In Guiana, Antiles, and Reunion, sugared pulp used to make a refreshing drink; also used for diarrhea.
- The Amerindians use the roots to treat epilepsy.
- Malays and Chinese use it as tonic.
Others
- Ritual: Fruit used in the New Year tradition of "bilog-bilog" for good luck - a bowlful collection of fruits (anonas, mansanas, ubas, pakwan, pinya, bayabas, etc) with other sundry items like cotton, salt, and coins.
- Dye: Leaves used in tanning, yields a blue or black dye.
- Fiber: Young twigs yield a superior fiber.
- Cosmetics: Used in cosmetic formulations. Juice expressed from fresh pulp used in shampoos to kill lice. (43)

Studies
• Phytochemicals / Acetogenins: Study isolated two annonaceous acetogenins from the seeds of Annona reticulata: squamone and isoannonareticin. (2)
• Anthelmintic / Seeds / Bark: Study showed the ethanol extract of Annona reticulata exhibited anthelmintic activity, taking less time to cause paralysis of the earthworms, Pheretima posthuma. Activity was attributed to a compound present in fraction 2 of the ethanol extract, which was the most potent. (3) Extracts from the bark of A reticulata showed potent anthelmintic activity. (6) An ethanol extract of seeds showed potent anthelmintic activity against Pheretima posthuma when compared to the chloroform extract, but less potent when compared to standard drug. (26)
• Annonacin / Cytotoxicity / Anti-Cancer: Study of annonacin isolated from the seeds of A reticulata showed it caused significant cell death in various cancer lines and suggests a potentially promising anticancer compound. (4)
• Antioxidant Study: In a study of antioxidant potential of leaves of three different species of Annona, A reticulata showed better activity in quenching DPPH and superoxide radical than A squamosa and A muricata. (5)
• Antibacterial: Study of antibacterial activity of different extracts of leaf of A. squamosa and A. reticulata showed the methanol extract to have the highest inhibition against B. subtilis, Staph epidermis, Staph aureus and Vibrio alginolyticus. (8)
• Antiproliferative: Study showed the ethanol extract of A. reticulata roots to have significant antiproliferative activity against A-549, K-562, HeLa and MDA-MB human cancer cell lines attributed to the collective presence of acetogenins, alkaloids and the lower inhibitory effect on Vero cell line. Results suggest a chemopreventive potential. (9)
• Kaur-16-en-19-oic Acid / Analgesic / Anti-Inflammatory: Kaur-16-en-19-oic acid, isolated from the bark of A. reticulata, exhibited significant analgesic and anti-inflammatory activity. (10)
• Insecticidal / Leaf Powder: Study of the insecticidal properties of A. reticulata and M. azedarach leaf powder against maize weevil, S. zeamais, showed that the presence of the plant materials in the diet significantly reduced the number of progeny, prolonged the developmental period and reduced the developmental index. (11)
• Insecticidal / Seeds: Study showed the seeds to have insecticidal activity. Phytochemical screening was positive for alkaloids, steroids, phenolic compound, cyanogenic compound, lipid.
• Reticulacenone / Acetogenin: Study yielded an acetogenin, reticulacinone, together with rolliniastatin-2 and molvizarin from a hexane extract of the stem bark of A. reticulata. (13)
• Antimicrobial / Leaves: A methanol leaf extract showed to possess antibacterial and antifungal activity and also remarkable antioxidant effect. (see constituents above) (14)
• Starch Content / Fruits: Pulp of Annona reticulata fruits yields about 19% starch. The purified starch has paste characteristics comparable to corn starch. (15)
• Annonaretin / Leaf Constituents / NO inhibition / Anti-Inflammatory: Study of leaves yielded annonaretin, a new triterpenoid, together with nine compounds. Most of the purified compounds exhibited significant inhibition of NO. Results suggest a potential for use of the leaves as a herbal medicine in the treatment of inflammatory diseases and the development of anti-inflammatory agents. (see constituents above) (16)
• Anthelmintic / Leaves / Roots: Crude extracts of leaves was evaluated for in vitro anthelmintic activity on Indian adult earthworms Eisinia fetida. Results showed dose-dependent inhibition of spontaneous motility. A methanolic extract showed anthelmintic activity comparable to reference drug Albendazole. (17) Study evaluated the roots of Annona reticulata for in vitro anthelmintic activity on adult Indian earthworm Pheretima posthuma at doses of 20, 40, and 60 mg/ml. Results showed the extract was effective at all concentrations, but especially so at 60 mg/ml. Activity was attributed to synergistic effects of phytoconstituents. (34)
• Analgesic / CNS Depressant / Bark: Various bark extracts were evaluated for evaluated for analgesic and CNS depressant activities in animal models. All extracts showed significant central analgesic activity and statistically significant mild to moderate CNS depressant activity. (18)
• Antihyperglycemic Effect / Leaves: Study evaluated a hydroalcoholic extract of leaves for hypoglycemic activity against STZ-induced hyperglycemic rats. Results showed significant improvement in fasting blood glucose and oral glucose tolerance test with improvement in biochemical and physical parameters. (19) Study of methanol extract of leaves on glucose-loaded mice showed dose-dependent and statistically significant strong antihyperglycemic activity. (25)
• Anticancer / Human Melanoma / Roots: Study evaluated ethanol and aqueous extracts of roots for in vivo anticancer activity against melanoma cells in mice and in vitro activity on MDA-MB-435 human melanoma cells. The ethanol extract significant reduced tumor growth and exhibited a prominent inhibitory effect against melanoma cell lines. The inhibitory effect may be attributed to the presence of acetogenins and alkaloids. (20)
• Antimicrobial / Antioxidant / Leaves: Study evaluated the antioxidant and antimicrobial properties of methanolic root extract of Annona reticulata. Results showed dose dependent scavenging on DPPH assay. The extract also showed significant activity against all strains of bacteria tested, with the largest zone of inhibition against B. cereus. (23)
• Antidermatophytic / Biosynthesis of Silver Nanoparticles / Leaves: Study investigated the biosynthesis of silver nanoparticles using A. reticulata leaf aqueous extract. The synthesized particles showed antidermatophytic activity suggesting potential as an antimycotic agent. (24)
• Chromium Adsorption: Study reported the removal of Cr (VI) by activated charcoal prepared from two natural materials, namely: Annona reticulata and Pouteria sapota. Both exhibited good adsorption of Cr (VI), with potential for practical applications for removal of Cr from effluents coming from tanneries. (27)
• Starch Binder for Tablet Formulation / Fruit Mucilage: Study showed the suitability of Annona reticulata fruit mucilage as a binder to paracetamol tablets. (28)
• Analgesic / Anti-Inflammatory / Stem Bark: Study of stem bark extract of A. reticulata showed significant analgesic activity in three test models (Writhing test, Tail flick test, and Tail immersion test) and significant anti-inflammatory activity against carrageenan and histamine induced paw edema. (30)
• Mosquito Larvicidal / Aedes aegypti / Leaves: Study showed crude extract of leaves possesses remarkable larvicidal activity against Aedes aegypti, presenting a potential herbal alternative to eradicate the mosquito population in the larval stage. (31)
• Mosquito Larvicidal / Culex quinquefasciatus / Roots: Study showed crude and ethyl acetate root extracts of A. reticulata can be effectively used as larvicidal against Cx. quinquefasciatus mosquito species at very low concentration. (32)
• Hepatoprotection / Antioxidant / Bark: Study evaluated fractions of A. reticulata bark against hepatotoxicity and inflammation using in vitro and in vivo models. Results demonstrated all bark fractions, methanol extract and water fraction exhibited strong antioxidant ability and showed protection against CCl4-induced toxicity in HepG2 cell lines in rats. Both fractions also exhibited dose dependent anti-inflammatory activity against carrageenan induced inflammation in rats. Activity was attributed to inhibition of oxidative stress and inflammatory cytokines. (33)
• Anticancer / Leaves: Study evaluated a methanolic extract of leaves for anticancer potential using sulforhodamine B (SRB) cytotoxicity against cancer cell lines viz. colon cancer (HCT15), Human lung cancer (Hop65), and Human hepatoma (HEPG2) cell lines. Results showed moderate anticancer activities attributed to anticancerous phytochemicals like acetogenins. (35)
• Nephroprotective / Gentamicin and Cisplatin Induced Nephrotoxicity / Aerial Parts: Study of ethanolic extract of aerial parts of A. reticulata showed nephroprotective activity in gentamicin and cisplatin induced nephrotoxicity in rat models attributed to therapeutic phytoconstituents. (36)
• Hepatoprotective / Simvastatin Induced Toxicity / Leaves:Study evaluated the hepatoprotective effect of ethanolic extract of leaves in simvastatin induced hepatotoxicity in liver cells. Results showed significant hepatoprotective activity especially at higher dose. Activity was comparable to that of silymarin. (37)
• Antimicrobial / Pericarp: Study investigated unripe and ripe pericarp extracts of A. reticulata fruits for in vitro antimicrobial properties against three gram-positive bacteria (B. subtilis, E. faecalis, and S. aureus), gram-negative bacteria (E. coli, P. aeruginosa, and P. vulgaris) and three fungal strains (A. flavus, A. niger, and P. chrysogenum). All the extracts showed activity against at least one strain of bacteria and fungi. The ethanol extract showed the unripe pericarp exhibited the highest inhibition activity against the growth of E. coli. (38)
• Hepatoprotective / Antioxidant / Bark: Study evaluated bioactive guided fractions of A. reticulata bark against hepatotoxicity and inflammation using in vitro and in vivo models. Among all fractions of bark, the methanol extract and water fraction showed strong antioxidant ability and hepatoprotection against CCL4 induced toxicity in HepG2 cells lines and rats. Both fractions also showed dose dependent anti-inflammatory activity against carrageenan inflammation in rats. Activity was attributed to inhibition of oxidative stress and inflammatory cytokines. (39)
• Antiulcer / Seeds: Study evaluated ethanolic extract of A. reticulata for antiulcer activity in a pyloric ligation ulcer model in rats. Results showed antiulcer activity with significantly (p<0.001) decreased gastric volume secretion (2.1mL), total acidity (92 meq/L/100g) and ulcer index (33.4). (40)
• Antiplasmodial / Antimalarial: Study of A. muricata and A. reticulata extracts showed antiplasmodial activity with IC50s of <10 µg/ml, without cytotoxicity. Extracts and fractions from leaf, twig, root, stem bark and fruit of A. reticulata showed activities against Plasmodium falciparum. (41)
• Antiulcer / Leaves: Study evaluated an aqueous extract of A. reticulata leaves for antiulcer potential using ethanol and indomethacin induced ulcer model in rats. Standard drug used was famotidine. The extract and famotidine showed significant decrease in acid volume and contents. The extract showed significant improvement in glutathione and pH level. The antiulcer activity may be due to cytoprotective, antisecretory, and antioxidant potential of phytoconstituents in the extract. (42)
• Inhibition of NO Production / Leaves: Study of leaves yielded nine compounds, including annonaretin A, a new triterpenoid. Most of the purified compounds exhibited significant NO inhibition of LPS-activated mouse peritoneal macrophages, with IC50s in the range of 48.6 ± 1.2 and 99.8 ± 0.4 µM. (44)
• Acute Toxicity Study / Leaves: Acute toxicity study evaluated the safety of usage of AR leaf extract in nutraceutical formulations according to OECD 423 guidelines using a single dose of 2000 mg/kbw via oral gavage for 4 days in female Swiss albino mice. Results showed no mortality, signs of toxicity and changes in behavior, with no significant differences (p<0.05) in body and organ weight, no significant changes in hematological and biochemical blood parameters, with histopath showing normal architecture in liver, kidney, and pancrease. Results suggest safety in oral administration and use in nutraceutical formulations. (45)
• Antiepileptic / Leaves: Study evaluated the antiepileptic activity of methanolic and aqueous extracts of leaves of A. reticulata on seizures induced by chemical and electroconvulsive method i.e. PTZ and MES methods in Swiss albino rats. Results showed antiepileptic activity, with % protection increasing with increase in dose, with dose of 400 mg/kg showing very good activity, with reduction in duration and delay in latency of seizures. (47)
• Wound Healing / Leaves: Study evaluated the wound healing effect of A. reticulata leaf extract invitro and in streptozotocin induced diabetic mice model. The extract increased proliferation and migration of HDF (primary human dermal fibroblast), skin fibroblast, and keratinocyte significantly in a dose dependent manner; and increased expression of TGF-ß, CTGF, VEGF, α-SMA, MMP-2, MMP-9, collagen-1, collagen-3, and FAK. Expression of CTGF (connective tissue growth factor) and α-SMA (alpha smooth muscle actin) also increased significantly in wound tissue.  Mass spectrometric analysis revealed two compounds in the extract: quercetin and ß-sitosterol. Results suggest the leaf extract possesses a stimulatory effect in diabetic wound healing. (51)
• Antinociceptive / Leaves: In a study of methanolic extract of A. reticulata leaves for antinociceptive effect in acetic acid-induced gastric pain model in Swiss albino mice, extract doses of 50, 100, 200, and 400 mg/kbw reduced number of writhings by 47.0, 55.1, 67.3 and 69.4%, respectively, comparing favorably with standard antinociceptive drug, aspirin. (52)
• Cytotoxicity / Recombinant Caspase Inhibitory Effect / Leaves: Caspases (Cysteine-dependent aspartate specific proteases) are involved in apoptosis (programmed cell death), inflammatory responses, and cellular proliferation and differentiation. Study evaluated the invitro cytotoxicity and recombinant caspase inhibitory effect of a methanol extract of A. reticulata leaves (MEAR). The MEAR was evaluated for cytoxicity against Caco-2 (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and HEK (human kidney carcinoma) cell lines. Doxorubicin was used as standard. The MEAR showed good dose-dependent cytotoxicity against both Caco-2 and HepG2 cell lines. MEAR at 5 and 10 µg/ml exhibited 56.02 and 66.64% inhibition against caspase-6 and 76.35 and 87.03% inhibition against caspase-9, respectively. Results suggest cytotoxicity to colon and liver cancer cells and may possess anticancer activity. (53)
• Immunomodulatory / Leaves: Study evaluated the effects of A. reticulata leaf ethanol extract on various components of the immune system. The extract stimulated proliferation of human PBMC, monocytes (THP1), and macrophages significantly. The extract activated cultured macrophages (U937), enhanced lymphocyte proliferation along with expression of interleukins in human PBMC. Extract treated mice showed strong DTH response with significant rise in antibody titer. Treatment augmented the expression of IL-2 and IL-6 in mice PBMC. Results suggest immunomodulatory potential. (54)

Availability
Wild-crafted and cultivated.