Annona squamosa L.

Last updated: 1 Jun 2016

Scientific Name

Annona squamosa L.

Synonyms

Annona asiatica L., Annona asiatica Vahl, Annona cinerea Dunal, Annona distincta Raeusch., Annona forskahlii DC., Annona forsskalii DC., Annona glabra Forssk. [Illegitimate], Annona squamosa Delile [Illegitimate], Guanabanus squamosus M. Gómez, Xylopia glabra L. [1]

Vernacular Name

Malaysia Nona sri kaya, buah nona, sri kaya [2]
English Sugar apple, sweetsop [2], custard apple, sweet sop of America [3]
China 番荔枝 (Fan li zhi) [4][5]
India Gandagaatra, sitaa phala, shubha, suda, ganda, gutea (Sanskrit); sharifaa, sitaphal (Hindi); sitaaphalam, siththa (Tamil); atta (Bengal, Sri Lanka); anusa (Gujerati); Seetapandu (Telagu); Sirpha (Malayalam) [3]
Indonesia Sirkaja (Javanese); sarikaja (Sundanese, Sumatra); atis (Ternate, Tidore) [2]
Thailand Noina (Central); makkhiap (North-eastern); lanang (Pattani) [2]; ma-o-chaa, manae, manonae, na-kloh-sae, noi naa, noinae [5]
Philippines Atis [2], ates, yates [5]
Cambodia Tiep baay, tiep srôk [2]
Vietnam Na, mang câù ta [2]
Nepal Aant, sarifa, shariphal [5]
Japan Ban-reishi [4]
France Attier, pomme cannelle [2]
Germany Zue-Kerapfel [3].

Geographical Distributions

Annona squamosa is widely distributed throughout tropical South America. Most atemoya hybrids resemble cherimoya in vigour and tree habit, but exhibit flowering and fruiting characteristics intermediate to both parents. It is grown commercially in Thailand, the Philippines and Malaysia, and the atemoya in Australia, Florida, Hawaii and Israel. [2]

Botanical Description

A. squamosa is a member of the Annonaceae family. It is a shrub or tree can grow up to 3-6 m tall. The leaves are oblong to narrowly elliptic, measuring 7-17 cm x 3-5.5 cm, slightly pubescent or glabrescent beneath. [2]

The flowers are extra-axillary, borne on slender peduncles of young branchlets and usually in clusters of 2-4 but sometimes solitary. The 3 outer petals are oblong, measure up to 2.5 cm long, green and purple at the base while the 3 inner petals are reduced to minute scales or absent. [2]

The fruit is a spherical or conical pseudocarp, measures 5-10 cm in diametre and formed of loosely cohering or virtually free carpels with the rounded ends projecting that render the tuberculate surface. The surface is greenish-yellow and with a powdery bloom. The pulp is white tinged with yellow. [2]

The seeds are oblong, deep brownish-black, compressed, with a pale swelling at the hilum or albumen filled with numerous transverse, brown lines of clefts. [6]

Cultivation

A. squamosa thrives in the tropics up to about 1000 m elevation and has the reputation of being a hardy, drought-resistant crop, particularly in India. This is only partly correct. Although the rest period and leaf fall enable the tree to survive a severe dry season, it requires adequate moisture during the growing season, and responds very well to supplementary irrigation. The importance of moisture is borne out by the fact that in India as well as Southeast Asia, fruit set is largely limited to the onset of the rains, notwithstanding the prolonged flowering season. [2]

Chemical Constituent

No documentation.

Plant Part Used

Leaves, bark, root, seeds and fruit. [6][7][8]

Traditional Use

The leaves, bark and unripe fruit is considered to possess strong astringent properties and this has been taken advantage of and used in the treatment of diarrhea and dysentery. [7] 

Fresh leaves when crushed and inserted into the nostrils can cut short fits of hysteria and faintaing according to Ayurvedic practitioners. Paste of the leaves is applied to non-healing ulcers [8]. The leaves has insecticidal activities and is used to remove head lice by applying a mixture of seed powder and leaf juice on the scalp. In Cuba, the leaves are taken to reduce gouty arthritis [7]. In Brazil the leaves forms part of a cough remedy syrup [6].

The fruits is considered invigorating, antibillious and antiemetic. The heart shaped fruit is considered a sedative to the heart. The fruits has expectorant properties and used to treat productive cough in India [7].  In Ayurveda the unripe fruit is given for diarrhea, dysenstery and atonic dyspepsia [8]. The dried powdered unripe fruits is used by the Indians to treat ulcers while the ripe fruit in paste form added to betel leaves form a good poultice to induce suppuration of tumours (abscesses)[7]. The Viadas on the other hand recommend bruising the ripe fruit and mixing it with salt to cause malignant tumours to suppurate [8].

The seeds are considered abortifacient and is applied to the uterus to procure abortion in India. [7][8]

The roots on the other hand is purgative and is used in the treatment of constipation and bloody dysentery [7]. Alkaloids from the roots exhibit antispasmodic activity and bronchodilatory properties. [6][7]

Preclinical Data

Pharmacology

Cytotoxic activity

Like other members of the Annonaceae family,  A. squamosa too have an array of acetogenin which produces cytotoxic effects. Amongst the acetogenin compounds isolated from various parts of the plant are bullatacin, bullatacinone and squamone from the bark, with tetrahydrosquamone and bullatacinone showing selectivity to MCF-7 human breast carcinoma [9]. Another compound isolated from the bark squamotacin also a bioactive acetogenin showed selectivity for hyuman prostate tumour cell line (PC-3) with a potency of over 100 million times that of Adriamycin [10]. Three mono-tetrahydrofuran (THF) ring acetogenins, each bearing two flanking hydroxyls and a carbonyl group at the C-9 position isolated again from the bark ((2,4-cis and trans)-Mosinone A, mosin B and mosin C) showed selectivity against human pancreatic tumour cell line, PACA-2, with potency 10-100 times that of Adriamycin [11]. It was further isolated three new annonaceous acetogenins, 4-deoxyannoreticuin, cis-4-deoxyannoreticuin, and (2,4-cis and trans)-squamoxinone which showed moderately significant cytotoxicities to six human tumour cell lines with (2,4-cis and trans)-squamoxinone showing selectivity against the pancreatic cell line (PACA-2) [12].  Another range of acetogenins was isolated from the bark of A. squamosa and identified bullacin to be selectively cytotoxic to MCF-7 (human breast adenocarcinoma) cell line [13].

The seeds of A. squamosa also contained annonaceous acetogenins which have cytotoxic activities. It was found that both organic and aqueous extracts induced apoptosis in MCF-7 and K-562 cells by nuclear condensation, DNA fragmentation, induction of reactive oxygen species (ROS0 generation and reduced intracellular glutathione levels suggesting that induction of apoptosis by both extracts is through oxidative stress [14]. Of the 8 mono-tetrahydrofuiran (THF)-type annonaceous acetogenis isolated and characterized,squadiolins A and B showed potency against human Hep G2 hepatoma cells and significant cytotoxic activity against human MDA-MB-231 breast cancer cells. Squafosacin B also exhibited significant cytotoxic activity against human Hep G2 and 3B hepatoma and MCF-7 breast cancer cells [15] .

Antimicrobial activity

Antiviral

The isolation of 14 kaurane derivatives and kaurane diterpines compounds had lead to the isolation of 16beta,17-dihydroxy-ent-kauran-19-oic acid. This compound showed significant activity against HIV replication in H9 lymphocyte cells with an EC50 value of 0.8 mg/mL. [16]

Anthelmintic

The seed extract of A. squamosa showed anthelmintic activity against sheep nematode Haemonchus contortus. The isolated compound was found to be able to inhibit the hatching of eggs of H. contortus. [17]

Antibacterial

From the leaf cuticular wax, two related compounds ie. 11-hydroxy-16-hentiaccontanone and its isomer 10-hydroxy-16-hentiacontanone was isolated and found to have antibacterial and antifungal activities when tested against selected Gram-positive and Gram-negative bacterial strains and selected fungal strains [18]. Essential oil distilled from the bark of A. squamosa showed significant antimicrobial activity against Baccillus subtilis and Staphylococcus aureus [19].

Antiheadlice

Various parts of A. squamosa has been used traditionally to eliminate headlice. It was found that the organic solvent extracts of the seeds and leaves were effective in reducing the population of headlice by up to 99% in a group of school girls. The petroleum ether extract seem to be the most effective even against benzyl benzoate emulsion [20]. An oleic acid and triglyceride were obtained with one oleate ester from the hexane seed extracts. These compounds were able to kill headlice within 11-50 minutes [21].

Anti-inflammatory and analgesic activity

Caryophyllene oxide was isolated from the unsaponified petroleum ether extract of bark of A. squamosa. This compound exhibit analgesic and anti-inflammatory activities in doses of 12.5 and 25 mg/kg body weight. The analgesic activity seems to be both centrally and peripherally mediated [22]. The seeds on the other hand contain cyclic peptides cyclosquamosin A, B, D, E, and H. The compound cyclosquamosin D was found to inhibit the production of pro-inflammatory cytokines within the lipopolysaccharide and Pam3Cys-stimulated J774A.1 macrophages [23]. 11 ent-kauranes were isolated from the stem of A. squamosa which showed immunomodulating effects in leukocytes [24]. In another study 16beta,17-dihydroxy-ent-kauran-19-oic acid was isolated. This compound show antioxidant along with anti-inflammatory activities [25].

Antioxidant activity

Water extract of the A. squamosa  leaves possess antioxidant activity as evidenced by increased activities of scavenging enzymes, catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutatione reductase (GR) and glutathione-s-transferase (GST) and decrease in malondialdehyde levels present in various tissues [26]. When compared to other Annona species (Annona reticulata & Annona muricata) the antioxidant activity of A. squamosa was the least effective [27].

Antidiabetic activity

Aqueous extract of the A. squamosa leaves showed antidiabetic activity by significantly reduced blood glucose, urea, uric acid and creatinine, but increased the activities of insulin, C-peptide, albumin, albumin/globulin ratio and restored all marker enzymes to near control levels [28][29]

Ethanol extract of the A. squamosa leaves possesses antidiabetic properties as seen in its ability to reduce fasting blood sugar level by 73% in STZ-induced diabetic rats and by 53% in severly diabetic rabbits. This extract also reduce the level of total cholesterol by 49%, the low-density lipoprotein (LDL) by 72%, triglycerides by 29% and increase high-density lipoprotein (HDL) by 30%. [30] 

It was found that quercetin-3-O-glucoside was responsible for most of the antidiabetic and antioxidant activities of the leaves of A. squamosa [32] .The fruit pulp was also found to posses antidiabetic properties [31]

Antihyperthyroidism activity

The A. squamosa seeds extract was evaluated for a possible ameliorative effect in the regulation of hyperthyroidism in mouse model. The results indicated that after 10 days of administration of the extract (200 mg/kg) all the effects of hyperthyroidism was reversed including a decrease in the hepatic lipid peroxidation. It was also found the the seed extract was more effective than propyl thiouracil (a standard antithyroid drug). Quercetin, a component of the extract, could be a mediator of the anti-hyperthyroid activity. [33]

Toxicity

No documentation.

Clinical Data

No documentation.

Dosage

No documentation.

Poisonous Management

No documentation.

Line drawing

 

83

Figure 1: The line drawing of A. squamosa [2]

References

  1. The Plant List. Ver1.1. Annona squamosa L. [homepage on the Internet]. c2013 [updated 2012 Apr 18; cited 2016 May 31]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2641034
  2. Annona squamosa L. In: Verheij EWM, Coronel RE, editors. Plant Resources of South-East Asia No. 2: Edible fruits and nuts. Wageningen, Netherlands: Pudoc; 1991.
  3. Panda H.  Herbs cultivation and medicinal uses. New Delhi: National Institute of Industrial Research, 2000; p. 144.
  4. Flora of China. Volume 19. Annona squamosa Linnaeus. [homepage on the Internet]. No date [cited 2016 Jun 09] Available from: http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200008509
  5. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume I A-B. Boca Raton, Florida: CRC Press, 2012; p. 312.
  6. Duke JA, Martinex RV. Amazonian ethnobotanical dictionary. Boca Raton, Florida: CRC Press, 1994; p. 22.
  7. Khare CP. Indian medicinal plants: An illustrated dictionary. Berlin: Springer, 2007; p. 53-54.
  8. Kapoor LD. CRC Handbook of Ayurvedic medicinal plants. Boca Raton, Florida: CRC Press, 1990; p. 41-42.
  9. Li XH, Hui YH, Rupprecht JK, et al. Bullatacin, bullatacinone, and squamone, a new bioactive acetogenin, from the bark of Annona squamosa. J Nat Prod. 1990;53(1):81-86.
  10. Hopp DC, Zeng L, Gu Z, McLaughlin JL. Squamotacin: An annonaceous acetogenin with cytotoxic selectivity for the human prostate tumor cell line (PC-3).  J Nat Prod. 1996;59(2):97-99
  11. Hopp DC, Zeng L, Gu ZM, Kozlowski JF, McLaughlin JL. Novel mono-tetrahydrofuran ring acetogenins, from the bark of Annona squamosa, showing cytotoxic selectivities for the human pancreatic carcinoma cell line, PACA-2. J Nat Prod. 1997;60(6):581-586.
  12. Hopp DC, Alali FQ, Gu ZM, McLaughlin JL. Mono-THF ring annonaceous acetogenins from Annona squamosa. Phytochemistry. 1998;47(5):803-809.
  13. Hopp DC, Alali FQ, Gu ZM, McLaughlin JL. Three new bioactive bis-adjacent THF-ring acetogenins from the bark of Annona squamosa. Bioorg Med Chem. 1998;6(5):569-575.
  14. Pardhasaradhi BV, Reddy M, Ali AM, Kumari AL, Khar A. Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: Role of reactive oxygen species and glutathione. J Biosci. 2005;30(2):237-244.
  15. Liaw CC, Yang YL, Chen M, et al. Mono-tetrahydrofuran annonaceous acetogenins from Annona squamosa as cytotoxic agents and calcium ion chelators. J Nat Prod. 2008;71(5):764-771.
  16. Wu YC, Hung YC, Chang FR, Cosentino M, Wang HK, Lee KH. Identification of ent-16 beta, 17-dihydroxykauran-19-oic acid as an anti-HIV principle and isolation of the new diterpenoids annosquamosins A and B from Annona squamosa. J Nat Prod. 1996;59(6):635-637.
  17. Souza MM, Bevilaqua CM, Morais SM, Costa CT, Silva AR, Braz-Filho R. Anthelmintic acetogenin from Annona squamosa L. seeds. An Acad Bras Cienc. 2008;80(2):271-217.
  18. Shanker KS, Kanjilal S, Rao BV, Kishore KH, Misra S, Prasad RB. Isolation and antimicrobial evaluation of isomeric hydroxy ketones in leaf cuticular waxes of Annona squamosa. Phytochem Anal. 2007;18(1):7-12.
  19. Chavan MJ, Shinde DB, Nirmal SA. Major volatile constituents of Annona squamosa L. bark. Nat Prod Res. 2006;20(8):754-757.
  20. Tiangda CH, Gritsanapan W, Sookvanichsilp N, Limchalearn A. Anti-headlice activity of a preparation of Annona squamosa seed extract. Southeast Asian J Trop Med Public Health. 2000;31 Suppl 1:174-177.
  21. Intaranongpai J, Chavasiri W, Gritsanapan W. Anti-head lice effect of Annona squamosa seeds. Southeast Asian J Trop Med Public Health. 2006;37(3):532-535.
  22. Chavan MJ, Wakte PS, Shinde DB. Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona squamosa L. bark. Phytomedicine. 2010;17(2):149-151. Epub 2009 Jul 2.
  23. Yang YL, Hua KF, Chuang PH, et al. New cyclic peptides from the seeds of Annona squamosa L. and their anti-inflammatory activities. J Agric Food Chem. 2008;56(2):386-392.
  24. Yang YL, Chang FR, Hwang TL, Chang WT, Wu YC. Inhibitory effects of ent-kauranes from the stems of Annona squamosa on superoxide anion generation by human neutrophils. Planta Med. 2004;70(3):256-258
  25. Yeh SH, Chang FR, Wu YC, Yang YL, Zhuo SK, Hwang TL. An anti-inflammatory ent-kaurane from the stems of Annona squamosa that inhibits various human neutrophil functions. Planta Med. 2005;71(10):904-909.
  26. Gupta RK, Kesari AN, Diwakar S, et al. In vivo evaluation of anti-oxidant and anti-lipidimic potential of Annona squamosa aqueous extract in Type 2 diabetic models. J Ethnopharmacol. 2008;118(1):21-25.
  27. Baskar R, Rajeswari V, Kumar TS. In vitro antioxidant studies in leaves of Annona species. Indian J Exp Biol. 2007 May;45(5):480-5.
  28. Kaleem M, Asif M, Ahmed QU, Bano B. Antidiabetic and antioxidant activity of Annona squamosa extract in streptozotocin-induced diabetic rats. Singapore Med J. 2006;47(8):670-675.
  29. Kaleem M, Medha P, Ahmed QU, Asif M, Bano B. Beneficial effects of Annona squamosa extract in streptozotocin-induced diabetic rats. Singapore Med J. 2008;49(10):800-804.
  30. Gupta RK, Kesari AN, Murthy PS, Chandra R, Tandon V, Watal G. Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals. J Ethnopharmacol. 2005;99(1):75-81.
  31. Panda S, Kar A. Antidiabetic and antioxidative effects of Annona squamosa leaves are possibly mediated through quercetin-3-O-glucoside. Biofactors. 2007;31(3-4):201-210.
  32. Gupta RK, Kesari AN, Watal G, Murthy PS, Chandra R, Tandon V. Nutritional and hypoglycemic effect of fruit pulp of Annona squamosa in normalhealthy and alloxan-induced diabetic rabbits. Ann Nutr Metab. 2005;49(6):407-413
  33. Panda S, Kar A. Annona squamosa seed extract in the regulation of hyperthyroidism and lipid-peroxidation in mice: possible involvement of quercetin. Phytomedicine. 2007;14(12):799-805.