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PHYTOCHEMISTRY AND PHARMACOLOGICAL ACTIVITIES OF ANNONA SQUAMOSA: REVIEW Chandraprakash Dwivedi 1 *, Corresponding Author: Chandraprakash Dwivedi * [email protected] Apollo College of Pharmacy, Anjora, Durg, Chhattisgarh 491001, India 1 ABSTACT: This review covers the pharmacological properties of different parts of Annona squamosa and biologically active constituents responsible for treatment potentials. A considerable attention to the benefits of biologically active chemicals could attribute to the development of potent drugs to certain pathologies. In various indigenous and traditional sources of medicine plants have been extensively used for Treatments. Various parts of plants such as the leaves, fruits, the barks,

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PHYTOCHEMISTRY AND PHARMACOLOGICAL ACTIVITIES OF

ANNONA SQUAMOSA: REVIEW

Chandraprakash Dwivedi1 *,

Corresponding Author:

Chandraprakash Dwivedi*

[email protected]

Apollo College of Pharmacy, Anjora, Durg, Chhattisgarh 491001, India1

ABSTACT:

This review covers the pharmacological properties of different parts of Annona squamosa and biologically active constituents responsible for treatment potentials. A considerable attention to the benefits of biologically active chemicals could attribute to the development of potent drugs to certain pathologies. In various indigenous and traditional sources of medicine plants have been extensively used for Treatments. Various parts of plants such as the leaves, fruits, the barks, roots and even the seeds are being used for preparation of medicine.

Keywords:- Cultivation , treatment, production, anti-cancer,drug

INTRODUCTION:

The genus name, ‘Annona’ is from the Latin word ‘anon’, meaning ‘yearly produce’, referring To the production of fruits of the various species in this genus. A. squamosa has been named botanically from Jamaica. Annona squamosa is also been extensively used as traditional medicine in various culture. Annona squamosal L. (Annonaceae), commonly known as the custard apple tree is a native of West Indies. But the cultivation is present throughout India, because of its edible nature.1 it is a fruit tree considered as a native of Central America also and hence have a wider cultivation throughout the regions of tropics. The taste of the pulp of the fruit is really sweet because of its higher sugar content of about 58% of dry mass, and hence it is found clear that the fruit pulp possess a high calorie value. This plant was reputed to contain several medicinal properties.2

The leaves of the plants have been used as insecticide, anthelmintic, styptic, externally used as suppurant. Unripe and dried Fruit work as antidysenteric. Bark is used as powerful astringent, antidysenteric and vermifuge. Rootbark, leaves and stems gave isoquinoline alkaloids. Powdered seeds are used to kill head-lice and fleas but care should be taken that the powder does not come in contact with the eyes as this causes great pain. Two acetogenins, annoreticuin and isoannoreticuin, isolated from the leaves, were found to be selectively cytotoxic to certain human tumours. The leaves and stems also gave alkaloids dopamine, salsolinol and coclaurine this article intends to provide an overview of the chemical constituents present in various parts of Annona squamosa Linn & their pharmacological actions.3, 4

GENERAL INFORMATION:-

Plant Profile

Scientific classification -

Domain: Eukaryota

Kingdom: Plantae

Class: Angiosperms

Division: Magnolids

Order: Magnoliales

Family: Annonaceae

Genus: Annona

Species: Reticulata

Botanical name: Annona retiulata

Synonyms: Shubha, Sitaphala

Common names: Custerd apple,

Vernacular names

Hindi: Sitaphal, Sharifa

Assamese: Atlas, Ata

Gujrat: Sitaphal

Punjub: Sharifa

Oriya: Ato

LOCAL NAMES5

Arabic (gishta) ; Bengali (ata); Creole (cachiman); Dutch (kannelappel); English (sweet sop,custard apple, sugar apple); Filipino (atis); French (cachiman canelle,pomme de cannelle,attier); German (Rahm-, Rahmapfel, Zimtapfel,Sübsack); Hindi (sitaphal,ata,sharifa) Indonesian (sarikaja,atis); Italian (pomo canella); Javanese (sirkaja); Khmer (tiep baay,tiep srôk); Lao (Sino-Tibetan) (khièb); Malay (nona sri kaya,sri kaya,buah nona); Mandarin (fan-li-chi); Portuguese (atta, fructa do conde); Sanskrit (sitaphal);Spanish (candongo,chirimoya,fructo do conde,anón,anona blanca,pinha,saramuya,anona); Swahili (mtomoko, mtopetope); Thai (lanang,makkhiap,noina); Urdu (sharifa); Vietnamese (na,mang câú ta).

Fig 1: Annona Squamosa Fruit and Seeds

BOTANIC DESCRIPTION 6

Annona squamosa is a small, semi-deciduous tree, 3-7 m in height, with a broad, open crown or irregularly spreading branches; bark light brown with visible leaf scars and smoothish to slightly fissured into plates; inner bark light yellow and slightly bitter; twigs become brown with light brown dots (lenticels). Leaves occur singly, 6-17 x 3-6 cm, lanceolate or oblong lanceolate, pale green on both surfaces and glabrate or nearly so; sides sometimes slightly

unequal; edges without teeth, inconspicuously hairy, at least when young, minutely dotted on examination with a lens; thin, dull green to dark green on top surface, and pale blue-green and covered with bloom on underside; apex short or long pointed; base short pointed or rounded; petioles 0.6-1.3 cm long, green, sparsely pubescent. Flowers greenish-yellow, fragrant, on slender hairy stalks, produced singly or in short lateral clusters about 2.5 cm long, 2-4 flowers but not at the base of the leaves; sepals pointed, hairy, green, about 16 mm long; 3 outer petals oblong, thick and rounded at the tips, fleshy, 1.6-2.5 cm long, 0.6 cm wide, yellow-green, slightly hairy, inside light yellow and keeled with a purplish or reddish spot at the thin, enlarged base; inner petals 3 minute, ovate, pointed scales; stamens very numerous, crowded, white, less than 16 mm long; ovary light green, styles white, crowded on the raised axis. The aggregate fruit formed from the numerous pistils of a flower, which are loosely united, is soft and distinct from other species of the genus. Each pistil forms a separate tubercle, mostly 1.3-1.9 cm long and 0.6-1.3 cm wide. Fruit is round, heart shaped, ovate or conical, 5-10 cm in diameter, with many round protuberances; greenish-yellow when ripe, with a white, powdery bloom; the pulp is white, edible and sweetly aromatic; in each carpel is embedded a seed, oblong, shiny and smooth, blackish or dark brown, 1.3-1.6 cm long, numerous. The genus name, ‘Annona’ is from the Latin word ‘anon’, meaning ‘yearly produce’, referring to the production of fruits of the various species in this genus. A. squamosa has been named botanically from Jamaica.

BIOLOGY7

Trees start to bear fruit when 3-4 years old. In Puerto Rico and the Virgin Islands, flowering and fruiting occur throughout the year. In India, the leaves fall in January-February and are renewed in April-May when the flowers appear, and fruiting is in July-August.

Origin and Distribution8

The custard apple is believed to be a native of the West Indies but it was carried in early times through Central America to southern Mexico. It has long been cultivated and naturalized as far south as Peru and Brazil. It is commonly grown in the Bahamas and occasionally in Bermuda and southern Florida.

Apparently it was introduced into tropical Africa early in the 17th century and it is grown in South Africa as a dooryard fruit tree. In India the tree is cultivated, especially around Calcutta, and runs wild in many areas. It has become fairly common on the east coast of Malaya, and more or less throughout southeast Asia and the Philippines though nowhere particularly esteemed. Eighty years ago it was reported as thoroughly naturalized in Guam. In Hawaii it is not well known.

Cultivars

No named cultivars are reported but there is considerable variation in the quality of fruit from different trees. The yellow-skinned types seem superior to the brownish, and, when well filled out, have thicker and juicier flesh. Seeds of a purple-skinned, purple-fleshed form, from Mexico, were planted in Florida and the tree has produced fruit of unremarkable quality.

Climate

The custard apple tree needs a tropical climate but with cooler winters than those of the west coast of Malaya. It flourishes in the coastal lowlands of Ecuador; is rare above 5,000 ft (1,500 m). In Guatemala, it is nearly always found below 4,000 ft (1,220 m). In India, it does well from the plains up to an elevation of 4,000 ft (1,220 m); in Ceylon, it cannot be grown above 3,000 ft (915 m). Around Luzon in the Philippines, it is common below 2,600 ft (800 m). It is too tender for California and trees introduced into Palestine succumbed to the cold. In southem Florida the leaves are shed at the first onset of cold weather and the tree is dormant all winter. Fully grown, it has survived temperatures of 27º to 28ºF (-2.78º to 2.22ºC) without serious harm. This species is less drought-tolerant than the sugar apple and prefers a more humid atmosphere.

Soil

The custard apple does best in low-lying, deep, rich soil with ample moisture and good drainage. It grows to full size on oolitic limestone in southern Florida and runs wild in light sand and various other types of soil in the New and Old World tropics but is doubtless less productive in the less desirable sites.

Propagation9

Seed is the usual means of propagation. Nevertheless, the tree can be multiplied by inarching, or by budding or grafting onto its own seedlings or onto soursop, sugar apple or pond apple rootstocks. Experiments in Mexico, utilizing cherimoya, llama, soursop, custard apple, Annona sp. Af. lutescens and Rollinia jimenezii Schlecht. as rootstocks showed best results when custard apple scions were side-grafted onto self-rootstock, soursop, or A. sp. Af. lutescens. Custard apple seedlings are frequently used as rootstocks for the soursop, sugar apple and atemoya.10

Culture

The tree is fast-growing and responds well to mulching, organic fertilizers and to frequent irrigation if there is dry weather during the growing period. The form of the tree may be improved by judicious pruning.11

Harvesting and Yield

The custard apple has the advantage of cropping in late winter and spring when the preferred members of the genus are not in season. It is picked when it has lost all green color and ripens without splitting so that it is readily sold in local markets. If picked green, it will not color well and will be of inferior quality. The tree is naturally a fairly heavy bearer. With adequate care, a mature tree will produce 75 to 100 lbs (34-45 kg) of fruits per year. The short twigs are shed after they have borne flowers and fruits.12, 13

Pests and Diseases

The custard apple is heavily attacked by the chalcid fly. Many if not all of the fruits on a tree may be mummified before maturity. In India, the ripening fruits must be covered with bags or nets to avoid damage from fruit bats. A dry charcoal rot was observed on the fruits in Assam in 1947. In 1957 and 1958 it made its appearance at Saharanpur. The causal fungus was identified as Diplodia annonae. The infection begins at the stem end of the fruit and gradually spreads until it covers the entire fruit.14,15

Food Uses

In India, the fruit is eaten only by the lower classes, out-of-hand. In Central America, Mexico and the West Indies, the fruit is appreciated by all. When fully ripe it is soft to the touch and the stem and attached core can be easily pulled out. The flesh may be scooped from the skin and eaten as is or served with light cream and a sprinkling of sugar. Often it is pressed through a sieve and added to milk shakes, custards or ice cream. I have made a delicious sauce for cake and puddings by blending the seeded flesh with mashed banana and a little cream.11,12

Food Value Per 100 g of Edible Portion*

Calories

80-101

Moisture

68.3-80.1 g

Protein

1.17-2.47 g

Fat

0.5-0.6 g

Carbohydrates

20-25.2 g

Crude Fiber

0.9-6.6 g

Ash

0.5-1.11 g

Calcium

17.6-27 mg

Phosphorus

14.7-32.1 mg

Iron

0.42-1.14 mg

Carotene

0.007-0.018 mg

Thiamine

0.075-0.119 mg

Riboflavin

0.086-0.175 mg

Niacin

0.528-1.190 m

Ascorbic Acid

15.0-44.4 mg

Nicotinic Acid

0.5 mg

*Minimum and maximum levels of constituents from analyses made in Central America, Philippines and elsewhere.

Toxicity

The seeds are so hard that they may be swallowed whole with no ill effects but the kernels are very toxic. The seeds, leaves and young fruits are insecticidal. The leaf juice kills lice. The bark contains 0.12% anonaine. Injection of an extract from the bark caused paralysis in a rear limb of an experimental toad. Sap from cut branches is acrid and irritant and can severely injure the eyes. The root bark has yielded 3 alkaloids: anonaine, liriodenine and reticuline (muricinine).16

Other Uses

The leaves have been employed in tanning and they yield a blue or black dye. A fiber derived from the young twigs is superior to the bark fiber from Annona squamosa. Custard apple wood is yellow, rather soft, fibrous but durable, moderately close-grained, with a specific gravity of 0.650. It has been used to make yokes for oxen.17

Medicinal Uses: 

The leaf decoction is given as a vermifuge. Crushed leaves or a paste of the flesh may be poulticed on boils, abscesses and ulcers. The unripe fruit is rich in tannin; is dried, pulverized and employed against diarrhea and dysentery. The bark is very astringent and the decoction is taken as a tonic and also as a remedy for diarrhea and dysentery. In severe cases, the leaves, bark and green fruits are all boiled together for 5 minutes in a liter of water to make an exceedingly potent decoction. Fragments of the root bark are packed around the gums to relieve toothache. The root decoction is taken as a febrifuge.18

PHARMACOLOGICAL ACTIVITIES:

Antibacterial and wound healing activity:

In the above study leaves of Annona squamosa (Linn.) were exhaustively extracted by soxhlet apparatus with different solvents like petroleum ether, solvent ether, chloroform, alcohol and chloroform water in ascending order of the polarity. All the five extracts were subjected to antibacterial screening by using the cup plate method. The petroleum ether, alcoholic and chloroform water extract showed maximum zone of inhibition. So these extracts were taken for wound healing activity. The petroleum ether extracts of Annona squamosa leaves were used in all models showed significant results.20 All the results were significant for different parameters in wound healing activity when compared with control group.11

The antibacterial screening by agar cup method indicates that highest zone of inhibition was shown by the methanol extract followed by petroleum ether and aqueous extracts for Annona squamosa leaf. Extracts of Annona squamosa inhibited the growth of all test strains except Salmonella typhimurium. Aqueous extracts showed less activity than methanol extracts possibly because i) the same active substances were present in water extracts, but in low concentrations ii) active substances were soluble in organic solvents and therefore, not present in water extracts . The antibacterial action of the extracts is more pronounced on Gram-positive than on Gramnegative bacteria, and these findings correlate to the observations of previous screenings of medicinal plants for antibacterial activity. Bacillus subtilis, Staphylococcus epidermidis, Staphylococcus aureus and Vibrio alginolyticus were the most sensitive bacterial strains in the present experiments. Annona squamosa had strong antibacterial activity against these bactirial stains.21, 22

Anti-tumor Activity

The defatted seed of Annona squamosa was screened for the antitumor activity.Cancers are the leading cause of death worldwide. In recent years, researchers have emphasized on the anti-tumor actions of seeds, pericarp and bark of herbs, and active plant chemicals have been identified for their anti-cancer properties.23 the seed oil exhibits anti-tumor activity in H22 xenograft bearing mice with a maximal inhibitory rate of 53.54% by oral route. The anti-tumor effect was proved to be down regulation of Interleukin-6/Jak/Stat3 signaling pathway by its main chemical constituents – unsaturated fatty acids. Annonaceous acetogens are recognized anticancer agents from Annona squamosa. 12,15-cissquamostatin-A and bullatacin were identified from seed oil and showed significant anti-cancer effects in human cancer cell lines and in H22 cells in mice . Squamoxinone-D was found selectively active against H460 cell line.24

The bark contains chemical constituents which have cytotoxic properties. Annosquamosin A, B and C, isolated from the bark have been shown to inhibit the growth of 95-D lung cancer cells and A2780 ovarian cancer cells. Treatment with the bark extract also reduced chromosomal aberration and the frequency of micronucleated polychromatic erythrocytes in 7, 12 dimethylbenz(a) antracene (DMBA)-induced genotoxicity in hamster models. Moreover, the bark extract reduces lipid peroxidation and potentiates antioxidant activities to inhibit tumor growth. Mosin A, B and C, annoreticuin-9-one, squamotacin, bullacin B, tetra hydrosquamone and bullatacinone have been demonstrated to have cytotoxic activities in different cancer lines.25, 26

Anticancer effect of Annona squamosa demonstrates selectivity for different cancer cells. In the study of Wang and colleagues, crude extract and ethanol acetate extract of Annona squamosa had significant anti-tumor actions on human epidermoid carcinoma cell line KB-3-1 and colon cancer cell line HCT-116 but not on hepatocellular carcinoma cell line BEL-7404, lung cancer line H460, prostatic cancer cell line DU145 and breast carcinoma cell line MDA-MB-435. Both leaf and seed extracts of Annona squamosa are active against Jurkat and HL60cell lines. Squamocin P and annosquatin III present in the seeds demonstrate selective inhibitory effect on SMMS 7721/T and MCF-7/ADR cell lines respectively.27

The extract was of aqueous and organic solvent. The parameter which was checked for the conclusion of the activity were estimation of intracellular ROS, estimation of intracellular GSH, DNA fragment analysis, and quantization of apoptosis. The study was carried out on rat histolytic cells tumor cell line AK-5. The study resulted significant apoptotic tumour cell death with enhanced caspase-3 activity, down regulation of antiapoptotic genes Bcl-2 and Bcl. Enhanced the generation of intracellular ROS, which correlated well with the decreased levels of intracellular GSH. In addition, DNA fragmentation and annexin-V staining confirmed that the extracts induced apoptosis in tumour cells through the oxidative stress. Aqueous extracts of A. squamosa seeds possessed significant antitumor activity in vivo against AK-5 tumor.28,29

Antidiabetic Activity:-

Study carried out on Annona squamosa have reviled that the plant posses antihyperglycemic effect. The study was done using Male albino Wistar rats. The diabeties was induced using streptozotocin. The study resulted that Oral administration of A. squamosal aqueous extract to diabetic rats for 30 days significantly reduced blood glucose, urea, uric acid and creatinine, but increased the activities of insulin, Cpeptide, albumin, albumin/globulin ratio and restored all marker enzymes to near control levels.30, 31

The present work has detected the antidiabetic activity of A. squamosa root extract in STZ induced hyperglycemia in rats. STZ induced diabetes mellitus and insulin deficiency lead to increased blood glucose level. When A. squamosa root extract was administered to diabetic rats, hypoglycaemia was observed after 2 hrs, with the maximum effect being seen at 6 h.From the results it is assumed that the root extract could be responsible for stimulation of insulin release and observed restoration of blood glucose level. Further, the observed decreased blood glucose lowering effect of the extract in STZ- induced diabetic rats could also possibly be due to increased peripheral glucose utilization.32 It has been reported that using medicinal plant extract to treat STZ-induced diabetic rats results in activation of ßcells and insulinogenic effects. The antihyperglycemic activity of the Aq. Extract of Annona squamosa roots was comparable with glibenclamide, a standard hypoglycaemic drug. the ethanolic extract of Annona squamosa Linn leaves posses considerable hypoglycemic activity in normal rats. The dose of 350 mg/kg body weight reduced the fasting blood glucose level by 6.0% within 1 h, whereas, the peak blood glucose at 1 h during glucose tolerance test was reduced by 17.1% in normal rats. Treatment of alloxan-induced diabetic rabbits for 15 days with a dose of 350 mg/kg of extract reduces fasting blood glucose by 52.7 % and urine sugar by 75%. The dose of 350 mg/kg body weight of ethanolic extract in 10-day treatment of a group of STZ-diabetic rats produced 73.3% fall in FBG level and no sugar was observed in fasting urine. An aqueous extract of A. squamosa leaves found to lower considerable fasting plasma glucose level in streptozoto cinnicotinamide induced type 2 diabetic rats. The findings of the study support the antidiabetic claims of A. squamosa.33, 34

Antihyperlipidemic Activity:-

This study shows the effect of Polyherbal formulation of Annona squamosa on blood glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in streptozotocin induced diabetic rats. Aqueous extract of Polyherbal formulation of Annona squamosa was administered orally (200 mg/kg body weight) for 30 days. The different doses of Polyherbal Formulation on blood glucose and plasma insulin in diabetic rats were studied and the levels of lipid peroxides and tissue lipids were also estimated in streptozotocin induced diabetic rats.35 The effects were compared with tolbutamide. Treatment with Polyherbal formulation and tolbutamide resulted in a significant reduction of blood glucose and increase in plasma insulin. Polyherbal formulation also resulted in a significant decrease in tissue lipids and lipid peroxide formation. The decreased lipid peroxides and tissue lipids clearly showed the antihyperlipidemic and antiperoxidative effect of Polyherbal formulation apart from its antidiabetic effect.36

Antioxidant – Activity:-

The free radical scavenging potential of the leaves of A. squamosa Linn was studied by using different antioxidant models of screening. The ethanolic extract at 1000 microg/ml showed maximum scavenging of the radical cation, 2,2-azinobis- (3- ethylbenzothiazoline-6 sulphonate) (ABTS) observed upto 99.07% followed by the scavenging of the stable radical 1,1-diphenyl, 2-picryl hydrazyl (DPPH) (89.77 %) and nitric oxide radical (73.64%) at the same concentration. However, the extract showed only moderate scavenging activity of superroxide radicals and antilipid peroxidation potential, which was performed using rat-brain homogenate. The findings justify the antioxidant activity of A. squamosa.37, 38

Insecticidal Activity:-

The present study investigatied Insecticidal activity of ethanolic extract of Annana squamosa.

The preliminary phytochemical investigation was carried out to identify the various constituents present in the extract.39, 40 It was found that the Annana squamosa contain alkaloids, protein, amino acid, carbohydrate, glycosides, phytosterols, tannins and phenolic compounds.The ethanol extract of Annona squamosa produced significant Knockdown” (KD50) in the Concentration 1% w/v and 5% w/v tested 23.1 min and 11.4 min for respectively. The mortality (100%) was achieved at 39.6±1.4 and 14.5±1. 1min for 1% w/v and 5% w/v concentration respectively. No mortality of the insects was found in any of the controls u“p to 100 hours.The ethanolic Annana squamosa extract showed potent activity against Sitophilus oryzae pest. The finding of new insecticidal activity is of great economic importance both from the agronomic and preventive medicine point of view.41, 42

Chemoprevantive & Antilipidperoxidative:-

The chemopreventive and antilpidperoxidative potential of Annona squamosa bark extracts in

DMBA induced hamster buccal pouch carcinogenesis.43 Oral squamous cell carcinoma was Induced in hamster buccal pouches by painting with 0.5% 7, 12-dimethylbenz (a) anthracene (DMBA) three times per week for 14 weeks. We observed 100% tumor formation in DMBA patient hamsters. Oral administration of aqueous & ethanolic bark extracts of Annona squamosa at a dose of 500 mg kg -1 body weight & 300 mg kg -1 body weight, respectively prevented the tumor formation as well as decreased the levels of lipid peroxidation by products & enhanced the antioxidants defens mechanism in DMBA painted hamsters. The effect of ethanolic bark extract is however more potent than aqueous extract of Annona squamosa barks. Our results suggest that Annona squamosa bark extracts exert their anticarcinogenic effect by modulating the status of lipid peroxidation & antioxidants in DMBA painted hamsters.44

Molluscicidal activity

In search for plant molluscicides for the vector control of schistosomiasis, Ethanolic extracts from A. squamosa Linn root was evaluated against adult forms and egg masses of Biomphalaria glabrata. Results from accurate experiments indicate that the analyzed extracts possess properties lethal to Biomphalaria glabrata .45The molluscicidal activity of leaves, bark and seed of A. squamosa against the snail Lymnaea acuminata was studied. The toxicity of powder from leaves, bark, and seed of custard apple against the snail was time - and dose -dependent. After 24h the toxicity of the seed (LC50=377.8 mg/litre) was higher than that of the leaf (LC50=381 mg/litre) and bark (LC50=458 mg/litre). The acetogenins extracted from the seed were highly toxic against the snail (LC 50=2 mg/litre at 96 h).46,47

Antiplasmodial activity

The antiplasmodial activity of methanolic extract of plant A. squamosa Linn was tested on chloroquine sensitive strain 3D7 and chloroquine resistant strain Dd2 of P. falciparum. The methanolic extract of A. squamosa leaves showed high antiplasmodial activity with IC50 values of 2 and 30 microg/ml on 3D7 and Dd2, respectively. While stem bark showed moderate activity with IC50 values of 8.5 and 120 microg/ml on Dd.48, 49

Leaf ethyl extract of Annona squamosa has promising antimalarial activity against chloroquine-sensitive and chloroquine resistant strains of Plasmodium falciparum N-Nitrosoxylopine, roemerolidine and Duguevalline isolated from Annona squamosa leaf extract are known alkaloids responsible for antimalarial properties .50, Similarly, the bark extract also exhibited IC50 of 30μg/ml against blood stage Plasmodium falciparum.51

Vasorelaxant activity

A cyclic octapeptide, cyclosquamosin B, isolated from the seeds of A. squamosa Linn showed a vasorelaxant effect on rat aorta. It showed a slow relaxation activity against norepinephrine (NE)- induced contractions of rat aorta with/without endothelium. 52,53It showed inhibition effect on vasocontraction of depolarized aorta with high concentration potassium, but moderately inhibition effect on NE-induced contraction in the presence of nicardipine. These results showed that the vasorelaxant effect by cyclosquamosin B might be attributed mainly to inhibition of calcium influx from extra cellular space through voltagedependent calcium channels54.

Anti-platelet activity

The ent-kaurane diterpenoids, which are isolated from stem of A. squamosa Linn are investigated for anti-platelet activity. The ent-kaurane diterpenoids ‘ent-Kaur-16-en-19-oic acid’ and ‘16alpha-hydro- 19-al-ent-kauran-17-oic acid’ showed complete inhibitory effects on rabbit platelet aggregation at 200 microM .55

Antifertility activity

The seed extract of A. squamosa Linn was investigated for post coitus antifertility activity.

The seed extract of A squamosa Linn shows antiimplantational and abortifacient activities56.

Antiviral activity

A kaurane diterpenoid 16β, 17-dihydroxy-entkauran- 19-oic acid was isolated from A. aquamosa Linn and investigated for their activity against HIV virus. The 16β, 17-dihydroxy-ent-kauran-19- oic acid showed significant activity against HIV replication in H9 lymphocyte cells56.

Antioxidant activity

For the study of antioxidant activity the leaves extract were used. The chemical constituent were isolated and was subjected to IR, LC-MS and the compound was confirmed flavones type compound on the basis of spectral data. The in vitro antioxidant activity of isolated compound Annona squamosa L was evaluated by free radical scavenging activity of different concentrations (10μg, 50 μg, and 100 μg) using 1, 1-diphenyl-2 picryl hydrazil method (DPPH). The results of assay were then compared with synthetic antioxidant Butylated hydroxyl anisole (BHA).The isolated compound exhibit (9.62, 24.28, and 45.62%) significant free radical scavenging activity 57.

Anti-arthritic, anti-inflammatory and analgesic activity

The above activities were screened using combined extract of Annona squamosa and Nigella sativa was evaluated and validated in various animal models.58 Arthritis was induced by Complete Freund`s Adjuvant (CFA) injection in metatarsal footpad of Sprague- Dawley rats. Degree of inflammation was evaluated by hind paw swelling and body weight, estimation of AST, ALT and TP supported by histopathology of knee joint. The result of combine extract was significant decrease in paw volume, increase body weight and reduction in elevated levels of ALT, AST and TP. For anti-arthritic activity the histopathological reviled the fact that there was significant reduction in neutrophils infiltration, pannus formation and bone of the animal

Treated with plant extract. The extract reviled that it has analgesic and anti-inflammatory activity in dose dependent manner when compared to comparable with the reference standard drugs, pethidine sulfate and indomethacin .59

MARKETED PRODUCT OF ANNONA SQUAMOSA:

Custard Apple Seed Oil 100% Natural Pure Undiluted Uncut Essential Oil 100 ML by Blooming Alley

Custard Apple Seed Oil (ANNONA SQUAMOSA) 100% Natural Pure Carrier Oil (30ml)

Healthvit Sitaphal /Sugar-Apple (Annona Squamosa) Powder 100gms The fruit is good for heart, skin, and bone, and maintains blood pressure.sitaphal is also helpful in curing of boils, ulcers and gum related problems. The bark of Sitaphal can be used in case of toothache and

gum pain.

Use: Mix 1 Teaspoon full of Sitaphal Powder in 200ml or as directed by physician.

Item details

Handmade item

Material

Custard Apple Seed Oil

100% Pure, Natural & Therapeutic Grade Custard Apple Seed Carrier Oil - 5ml to 500mlAromatic Description: It has a sweet, woodsy aroma.

CONCLUSION:

The extensive survey literature reviewed that Annona squamosa Linn, is an important medicinal plant with diverse pharmacological spectrum annona squamosal which is commonly known as custard apple in English and sitafal in Hindi having various pharmacological activity such ad antidiabetic, analgesic, anti-inflammatory, wound healing, antimalarial, cytotoxic, anti-oxidant, anti-microbial and few more. Some compounds have been isolated and reported from the extract of various part of the plant possessing good pharmacological activity.

REFERENCE:

1. Win Min Oo, Myat Mon Khine, Pharmacological Activities of Annona squamosa: Updated Review, International Journal of Pharmacy and Chemistry 2017; 3(6): 86-93.

2. Kapoor L.D ( 2005), Hand book of Ayurvedic Medicinal Plants, CRC Press LLC, First Indian, Reprint, p. 41–42, ISBN No. 0-8493- 2929-9.

3. Sathe MV; Chaudhari BG; Singh SP; Hole AD (2006), Pharmacognostical study of Annona squamosa Linn. Leaf. Regional Res. Institute (Ay.) Pune – Paper communicated for publication to CCRAS, New Delhi.

4. Chopra RN; Chopra IC; Varma BS (1998), Supplement to Glossary of Indian Medicinal Plants, National Institute of Science Commun ication, CSIR, New Delhi.

5. Morton J. (1987), Sugar apple. Fruits Warm Climate. 69–72.

6. Mishra A.; Dogra J. V.V.; Singh J.N; Jha (1979), Post-coital antifertility activity of Annona squamosal and Ipomea fistulosa. Planta Medica. 35: 283–285.

7. Forgacs, P., Desconclois, J. F., Provost, R. and Tiberghien et Touche (1980), A., Un Nouvel Heteroside Nitre Extrait D’ Annona squamosa. Phytochemistry 19: 1251–1252.

8. Yang T. H. and Chi-Ming C. (1972), Structure of squamolone, a novel diazepine from Annona squamosal, L. J. Chin. Chem. Society. (Taipei). 19: 149–151.

9. The Wealth of India (Raw Materials), Revised edition,( 2003), Council of Industrial and Scientific Research, New Delhi, 279–294.

10. Chopra. R.N. ; Nayar. S.L. (1986), Glossary of Indian Medicinal Plants, Council of Scientific and Industrial Research, New Delhi.

11. Li X. H; Hui Y. H; and Rupprecht J. K.(1990), Bullatatacin, bullatacinone, and squamone: a new acetogenin from the bark of Annona squamosa. J. Natural Product. 53: 81–86.

12. Fujimoto Y et al. (1988), Squamocin, a new cytotoxic bis-tetrahydrofuran containing acetogenin from Annona squamosa, Chem. Pharm. Bull. (Tokyo).36(12) : 4802-4806.

13. Kirtikar KR and Basu BD: Indian Medicinal Plants, Published by International Distributors, Edition 2, Vol.1, 66-68.

14. The Wealth of India, A Dictionary of India Raw Material and Industrial Products, Second Supplement Series Raw Material, Published and Printed by National Institute of Science Communication and Scientic and Industrial Research, Vol. A-F, 72-73.

15. Morton and Julia: Fruits warm of climate Annona squamosa, 2013; 6: 69. Natural Resources Conservation Service (NRCS), Plants Annona squamosa United States Department of Agriculture 2008: 4-17.

16. Germplasm Resources Information Network (GRIN), Taxonomy for Plants. USDA, ARS, National Genetic Resources Program 1997: 7-11.

17. Wunderlin R and Hansen B: Synonyms of Annona squamosa Atlas of Florida Vascular Plants 2008; 24-27.

18. Raj SD, Vennila JJ, Aiyavu C and Selvam P: The heapatoprotective effect of alcoholic extract of Annona squamosa leaves on experimentally induced liver injury in swiss albino mice. International Journal of Integrative Biology 2009; 5(3):182-186.

19. Crane JH, Balerdi CF and Maguire I: Sugar apple growing in the Florida Home Landscape 1994; 4:4-19.

20. Chitra Shenoy, M B Patil and Ravi Kumar, Antibacterial and Wound Healing Activity of the Leaves of Annona squamosa Linn, Research Journal of Pharmacognosy andn phytochemistry ,Volume 01, Issue 01, July- August, 2009.

21. A Dholvitayakhun, N Trachoo, U Sakee, and TP Cushnie, Potential applications for Annona squamosa leaf extract in the treatment and prevention of foodborne bacterial disease, Nat Prod Commun, 8 (2013) 385-388.

22. P Shokeen, K Ray, M Bala, and V Tandon, Preliminary studies on activity of Ocimum sanctum, Drynaria quercifolia, and Annona squamosaagainst Neisseria gonorrhoeae, Sex Transm Dis, 32 (2005) 106-111.

23. LP Padhi, SK Panda, SN Satapathy, and SK Dutta, In vitro evaluation of antibacterial potential of Annona squamosa L. and Annona reticulata L. from similipal biosphere reserve, Orissa, India., J AgriTech, 7 (2011) 133-142.

24. M Yusha'u, DW taura, B bello, and N Abdullahi, Screening of Annona squamosa extracts for antibacterial activity against some respiratory tract isolates, Int Res J Phar Pharmacol, 1 (2011) 237-241.

25. KS Shanker, S Kanjilal, BV Rao, KW Kishore, S Misra, and RB Prasad, Isolation and antimicrobial evaluation of isomeric hydroxy ketones in leaf cuticular waxes of Annona squamosa,Phytochem Anal, 18 (2007) 7-12

26. MM Rahman, S Parvin, M Ekramul Haque, ME Islam, and MA Mosaddik, Antimicrobial and cytotoxic constituents from the seeds of Annona squamosa, Fitoterapia, 76 (2005) 484- 489.

27. HM Kotkar, HM, PS Mendki, SV Sadan, SR Jha, SM Upasani, and VL Maheshwari, Antimicrobial and pesticidal activity of partially purified flavonoids of Annona squamosa, Pest Manag Sci, 58 (2002) 33-37.

28. JBS Kachhawa, N Sharma, S Tyagi, and KK Sharma, Screening of stem bark methanol extract of Annona squamosal for antibacterial activity, Inter J CurrPharm Res, 4 (2012) 48- 50.

29. P Taylor, M Arsenak, MJ Abad, A Fernandez, B Milano, R Gonto, MC Ruiz, et al., Screening of venezuelan medicinal plant extracts for cytostatic and cytotoxic activity against Tumor cell lines, Phytother Res, 27 (2013) 530-539.

30. RM Yang, WM Li, WJ Hu, WH Huang, CY Zhu, JG Yu, X Zhao, DY Cai, and NN Gao, Anticancer effect of total annonaceous acetogenins on hepatocarcinoma, Chin J Integr Med, 21 (2015) 682-688.

31. Y Miao, X Xu, F Yuan, Y Shi, Y Chen, J Chen, and X Li, Four cytotoxic annonaceous acetogenins from the seeds of Annona squamosa, Nat Prod Res 30 (2016): 1273-1279.

32. Y Chen, J Chem, Y Wang, S Xu, and X Li, Six cytotoxic annonaceous acetogenins from Annona squamosa seeds, Food Chem 135 (2012): 960-966.

33. HJ Yang, N Zhang, JW Chen, and MY Wang, Two new cytotoxic acetogenins from Annona squamosa, JAsian NatProd Res 11 (2009) 250-256.

34. BV Pardhasaradhi, M Reddy, AM Kumari, AL Ali, and A Khar, Differential cytotoxic effects of Annona squamosa seed extracts on human tumor cell lines: role of reactive oxygen species and glutathione, J Biosci, 30 (2005): 237-244

35. BV Pardhasaradhi, M Reddy, AM Ali, AL Kumari, and A Khar, Antitumor activity of Annona squamosa seed extracts is through the generation of free radicals and induciton of apoptosis, Indian J biochem Biophys 41 (2004) 167-172.

36. DC Hopp, L Zeng, Z Gu, and JL McLaughlin, Squamotacin: an annonaceous acetogenin with cytotoxic selectivity for the human prostate tumor cell line (PC-3), J Nat Prod,59 (1996) 97-99.

37. L Sun, H Zhu, L Gan, J Mo, F Feng, and C Zhou, Constituents from the bark of Annona squamosaand their anti-tumor activity, Zhongguo Zhong Yao Z Zhi. 37 (2012) 2100-2104

38. K Suresh, S Manoharn, and D Blessy, Protective role of Annona squamosa linn bark extracts in DMBA induced genotoxicity, Kathmandu Univ Med J 6 (2008) 364-369.

39. K Suresh, S Manoharan, K Panjamurthy, and K Kavitha, Chemoprotective and antilipidperoxidative efficacy of Annona squamosa bark extracts in experimental oral carcinogenesis, Pak Jf Bio Sci, 9 (2006) 2600-2605.

40. Khar Ashok, Antitumour activity of Annona squamosa seed extracts is through the generation of free radicals and induction of apoptosis, Indian Journal of Biochemistry & Biophysics Vol. 41, August 2004, pp. 167- 172.

41. Kaleem M, Medha P, Ahmed Q U, Asif M, Bano B, Beneficial effects of Annona squamosa extract in streptozotocin-induced diabetic rats, Singapore Med J, 2008; 49 (10) : 800.

42. RK Gupta, AN Kesari, PS Murthy, R Chandra, V Tandon, and G Watal, Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals, J Ethnopharmacol, 99 (2005) 75-81.

43. R Sangala, S Burra, J Gopu, DR Kodati, and Dubai A, Evaluation of antidiabetic activity of Annona squamosa Linn seed in Alloxan-induced diabetic rats, Int J Preclin Res, 2 (2011) 100-106.

44. RS Tomar, and SS Sisodia, Antidiabetic activity of Annona squamosa L. in experimental induced diabetic rats, Inter JPharm Biol Arch, 3 (2012) 1492-1495.

45. Santos A.F., Sant'Ana A.E., Phytomedicine.2001 Mar;8(2):115-20.

46. Panda S., Kar A., Phytomedicine. 2007Dec;14(12):799-805

47. HM Kotkar, HM, PS Mendki, SV Sadan, SR Jha, SM Upasani, and VL Maheshwari, Antimicrobial and pesticidal activity of partially purified flavonoids of Annona squamosa,Pest Manag Sci, 58 (2002) 33-37.

48. A Bagavan, AA Rahuman, NK Kaushik, and D Sahal, In vitro antimalarial activity of medicinal plant extracts against Plasmodium falciparum, Parasitol Res, 108 (2011) 15-22.

49. A EI-Tahir, GM Satti, and SA Khalid, Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on Maytenus senegalensis (lam.) Exell, J Ethnopharmacol, 64 (1999) 227-233.

50. Magadula J. Joseph, Innocent Ester, Otieno .N .Joseph. “Mosquito larvicidal and cytotoxic activities of 3 Annona species and isolation of active principles”. Journal of Medicinal Plant Research; 2009, 3(9), pp 674-680.

51. N Singh, NK Kaushik, D Mohanakrishnan, SK Tiwari, and D Sahal, Antiplasmodial activity of medicinal plants from Chhotanagpur plateau, Jharkhand, India, J Ethnopharmacol 13(2015) 152-162.

52. T Johns, A Windust, T Jurgens, and SM Mansor, Antimalarial alkaloids isolated from Annona squamosa, Phytopharm, 1 (2011) 49-53.

53. C Kamaraj, NK Kaushik, D Mohanakrishnan, G Elango, A Bagavan, AA Zahir, AA Rahuman, and D Sahal, Antiplasmodial potential of medicinal plant extracts from Malaiyur and Javadhu hills of South India, Parasitol Res, 111 (2012) 703-715.

54. H Morita, T Iizuka, CY Choo, KL Chan, K Takeya, and J Kobayashi, Vasorelaxant activity of cyclic peptide, cyclo squamosin B, from Annona squamosa, Bioorg Med Chem Lett,16 (2006) 4609-4611.

55. Yang Y.L., Chang F.R., Wu C.C., Wang W.Y., Wu Y.C., J Nat Prod. 2002 Oct; 65(10):1462- 7.

56. Mishar A., Dogra J.V., Singh J.N., Jha O.P., Planta Medica, 1979 Mar;35(3):283-285.

57. Wu Y. C., Hung Y.C., Chang F. R., Cosentino M., Wang H.K. and Lee K.H., J. Nat. Prod. 1996 Jun (59), 635-637.

58. C. Chandrashekar et al, Isolation,Characterizations and Free radical scavenging activity of Annona squamosa leaf, Journal of Pharmacy Research 2011,4(3),610- 611.

59. RY Ibrahim, AI Hassan, and EK AI-adham, the antiulcerative colitis effects of Annona squamosa Linn. Leaf aqueous extract in experimental animal model, Int J Clin Exp Med, 8 (2015): 21861-21870.