Positive Health Online

Authors:  ¹Yostan Absalom Labola SPd MSi.Gr, ²Diana Rosanti

¹ASN GGD 2016, South Central Timor Regency, ²Student of Physics Education, Faculty of Teacher Training and Education, University of Mulawarman

1. Description of Annona Squamosa Linn

Annona Squamosa Linn is a small irregular branching shrubs of the family Annonaceae.  Annona Squamosa grown as high as 3-8 in the tropics. This plant is found in the country of India, America, Brazil, Southern Florida (Kaleem et al., 2008) and in some other areas such as Indonesia.

In English this plant called Annona squamosa/sugar apple (United Kingdom), Srikaya (Indonesia), and for the people in the eastern part of Indonesia, the province of East Nusa Tenggara, the plant is called 'Annonak'.

In Indonesia, many annona squamosa found in the eastern part (East Nusa Tenggara Province, South Central Timor Regency) life without the people page of cultivated and wild life in the wealds (Labola, 2017).

Annona squamosa is an important crop in the medical world but not yet exploited optimally. In fact, there is a lot of research has been informed that annona squamosa have pharmacological activity (Raj et al., 2009; Kaleem et al., 2008).

This review informs the compounds contained in annona squamosa, pharmacological activity and its benefits for human health. Investigation and evaluation of advanced against potential on parts of plant utilization in the world for the sake of annona squamosa health is indispensable.

2. Morphological of Annona Squamosa Linn (shown figure below)

a. Stem and Leaf

Stems and branches of colored light brown annona squamosa with leaf scars. While the skin in in yellow, bitter taste. The leaves are elliptical oval shaped pale green long-sized 6-17 cm and 3-6 cm in width (Saha, 2011; Kalidindi et al., 2015).

b. Flower

Flowers greenish yellow, fragrant, and slim hairy flower stalks. Lateral cluster produced with 2-4 cm. length On petals oblong, fleshy with a length of 1.6-2.5 cm and width 0.6 cm yellow green. On the outer petals are green, purplish at the base of the stamens and very much with the size of the length of white.

c. Fruit

Young fruit is green and ripe fruit is yellow-green, round shapes like hearts (Evergreen/fruit cone). Mature fruit diameter (6-10) cm with lump skin and flaky white flesh of the fruit with the taste of sweet food.

d. Seed

Each seed contains carpels stretching. Young fruit to smooth Brown seeds. In ripe fruits, seeds black shiny and smooth with long size (1, 3-1, 6) cm.

3. Phytochemical Contained

There are a number of biochemical compounds contained in the plant parts of annona squamosa. The existence of biochemical compounds depending on the solvent used when extracting. Some compounds that have been summarized from the study of literature include the following (a) Leaf : Steroids, Triterpine, Glycoside, Flavonoids, Alkaloids, Saponins and Phinolic (b) skin : N-Nitrosoxylopine, Roemerolidine, and Duguevalline, (c) root : liriodenine and oxoanalobine group oxoaporphines (Souza et al., 2008) norcorydine, isocorydine, Norushinsunine, etc, (d) Seeds : Annonastatin, asimicin, squamocin, essential oils like β farnesene, β-pirene, αpirene, limorene etc, (e) Fruit : kaurane-type diterpenes, (-)-ent-kaur-16-en-19-oic acid and 16α,17-dihydroxy-ent-kauran-19 oic acid (Saluja et al., 1990 ; Bhakuni et al., 1972 ; Chao-Ming et al., 1997 ; Hopp et al., 1996 ; Hopp et al., 1998 ; Yang and Chen., 1970 ; Oliver-Bever et al., 1986).   

4. Pharmacological Activity and Health Benefits

a. Anti-malaria Activity

Some of aporphine alkaloids isolated from bark annona squamosa. The structure of compounds identified as N-Nitrosoxylopine, Roemerolidine and Duguevalline. These compounds is antimalarial activity filtering. Aporphine alkaloid was isolated in vitro is active with IC50 values antiplasmodial range between 7.8 and 34.2 μM/mL (Saha, 2011). For the compound N-Nitrosoxylopine, antiplasmodial activity shows the large and cytotoxicity that might be caused by nitroso compounds existing moiety of the compound (Kulkarni and Chandershekhar, 2011). On the Roemerolidine and Duguevalline compounds show moderate antiplasmodial activity without cytotoxicity.

Leaf extract with the solvent ethyl antimalarial activity (Bagavan et al., 2011;  EI-Tahir et al., 1999; Singh et al., 2015). Skin extract also showed the IC50 of 30μg/ml against Plasmodium falciparum (Kamaraj et al., 2012).

b. Anti-diabetic Activity

Studies show that the plant has antihyperglycemic effect. Kaleem el al (2008) suggests, giving oral Annona squamosa extracts during 30 days significantly reduced blood glucose, urea, uric acid and creatinine, but increased the activities of insulin, peptide, albumin, albumin/globulin ratio and restored all marker enzymes to near control levels. In addition, it was found exhibited cytotoxicity as well which might be attributed to nitroso compounds existing moiety of the compound (Kulkarni and Chandershekhar, 2011).

Leaf extract, seeds and roots have the effect of antidiabetic and hypoglycemic (Gupta et al., 2005; Shirwaikar et al., 2004; Mohd et al., 2009; Sangala et al., 2011; Tomar and Sisodia, 2012). Ren et al (2017) reported that acid heteropolysaccharide is known as GASP3-3-I was isolated from the pulp of the fruit responsible for inhibition of the enzyme alpha-glycosidase.  While Quercetin-3-O-Glycoside isolated from the leaves of annona squamosa inhibits the activity of the glucose 6 Phosphatase in the liver and lowering blood glucose levels (Panda and Kar, 2007). The combined therapy on leaf extract and Glipizide prove useful in the reduction of the dose of Glipizide to 50% (Kaur et al., 2013).

c. Anti-tumour Activity

Research conducted for tumour cells of the rat histolytic AK-5 with checks on parameter estimation of intracellular ROS, estimation of intracellular GSH, analysis of DNA fragments, and quantization apoptosis. Obtained results that occurred the death of tumor cells apoptosis significantly with an increase in caspase-3 activity, setting down the genes of antiapoptotic Bcl-2 and Bcl. DNA fragmentation and staining On annexin-V confirmed that extracts induce apoptosis in tumour cells through oxidative stress. Aqueous extract of seed of annona squmosa has significant antitumor activity in vivo against AK-5 tumours (Ashok, 2004).

Compound of annonaceous anticancer agent known as acetogens of annona squamosa (which el al., 2015). 12.15-cissquamostatin-A and bullatacin identified from oil seeds and anti-cancer effect shows that significant in human cancer cell lines (Chen et al., 2012).

 Squadiol A and B showed significant cytotoxic effect on MDA-MB-231 breast cancer cells and breast cancer cells MCF-7 (Liaw et al., 2008). Annosquacin A, B and C, annosquatin A and B, and squamostanin A, B and D, squamostolide, bullatacin and uvarigrandin A has antitumour properties (Xie et al., 2003; The et al., 2009; Chen et al., 2011; Chen et al., 2012).

Annosquamosin A, B and C was isolated from the bark has been shown to inhibit the growth of 95-D cells of lung cancer and ovarian cancer cells A2780 (Sun et al., 2012). In addition, extracts of bark reduces the concentration of lipids and antioxidant activity of inhibiting tumor growth (Suresh et al., 2006). Model A, B and C, annoreticuin-9-one, squamotacin, bullacin B, tetrahydrosquamone, and bullatacinone have cytotoxic activity on cancer (Hopp et al., 1997; Hopp et al., 1996; Hopp et al., 1998; Li et al.,1990).

Leaf extract has potential treatment leukaemia cell lymphoma T/a cytotoxic effect for promising (Nakano et al., 2013). O-methylarmepavine and trihidroksi bistetrahydrofuran C37 acetogenins have cytotoxic properties (Vila-Nova et al., 2011). Extract crude and ethanol extracts of acetate annona squamosa have the action of anti-tumour cell line of a significant human epidermoid carcinoma KB-3-1 and colonic cancer cell line HCT-116 (Wang et al., 2014).

d. Anti-ulcer Activity

1-(4-beta-D-glucopyranosyloxyphenyl)-2-(n-Dllucopyranosyloxy)-isans compounds isolated from the branch there is in vivo anti-secretory activity and decreased plasma gastrin levels (Saha, 2011, Yadav and Singh, 2011 ).

Annona squamosa twigs contains active constituents and protect peptikum ulcer. (+)-O-methylarmepavine, Nmethylcorydaldine and isocorydine have anti-sekretorik reduces acidity of gastric pepsin and gastrin levels, and inhibiting the H-K ATPase pumps (Yadav et al., 2012). Leaf extract proved are protective of aspirin plus ligation of pylorus (Alluri et al., 2011).

e. Hepatoprotective Activity

The results of leaf extract with water and alcohol were incapable of healing total liver damage caused by isoniazid and rifampicin. May limit the effects of these drugs in the liver (Saleem TS, 2008).

Hydrocalohol seed extract annona squamosa hepatoprotective against CCl-4 induced hepatotoxicity at doses of 100mg / kg, 200mg / kg and 400mg / kg (Mehta and Paliwal, 2017).

f. Wound Healing Activity

Results of a study on the leaf with solvent petroleum ether, chloroform and alcohol showed maximum inhibition zone of activity for wound healing. Significant results for the different parameters in the wound healing activity when compared with the control group (Shenoy et al., 2009).

Leaf extract with ethanol enhances wound healing by increasing collagen synthesis, synthesis of glikosaminoglikan, cellular proliferation in injured part (Ponrasu and Suguna, 2012; Ponrasu and Suguna, 2014).

g. Anthelmintic activity

Results extracts on seed with water and methanol showed Anthelmintic activity of Haemonchus contortus significantly to that. While the analysis of ethyl acetate extract of spectroscopy there is compound trihidroksi bistetrahidrofuran adjoining C37 acetogenin that inhibit the hatching eggs of H. contortus (Souza and Bevilaqua, 2008).

h. Anti-rheumatic Activity

The result of the combined extract annona squamosa and Nigella sativa significant volumes of paw, promote weight loss and reduction in levels of ALT, AST and TP anti rheumatic activity. There is a significant reduction in neutrophil infiltration, pannus formation and bones of animals treated with plant extracts.

i. Analgesic and Anti-Inflammatory Activity

Anti-inflammatory and analgesic activity significantly depends on the dose when compared to standard drug reference, pethidine sulfate and indomethacin (Sanjiv, 2011).

The cyclic peptide fanlizhicyclopeptide A and fanlizhicyclopeptide B isolated from pericarp reduces the generation of TNF-pronounced and IL-6 in the macrophages (Wu et al., 2014). In addition, 18-acetoxy-ent-kaur-16-ene isolated from Annona squamosa skin responsible for the anti-inflammatory and analgesic action at 50 mg/kg dose (Chavan et al., 2011).

Caryophyllene oxide isolated from the skin of annona squamosa have the effect of analgesic and anti-inflammatory with a dose of 12,5-25 mg/kg body weight (Chavan et al., 2010). 16beta, 17-dihydroxy-ent kauran--19-oic acid isolated from the skin of annona squamosa inhibit the production of superoxide and release elastase (Yeh et al., 2005).

Cyclosquamosin cherimolacyclopeptide D and B isolated from the seeds of proinflamasi generation of cytokines inhibit the annona squamosa such as IL-6 and TNF-pronounced in activated macrophages (which et al., 2007; Dellai et al., 2010).

j. Anti-microbial Activity

Annona squamosa extract results with solvent petroleum ether and methanol to check the antibacterial activity show that the highest inhibition zones were observed in methanol extracts against PS. Aeruginosa (MIC: 130 μg/ml) was followed by extracts petroleum ether against PS. aeruginosa (MIC: 165 μg/ml) and methanol extracts against e. coli (MIC: 180 μg/ml) (Jayshree et al., 2008). In line with research results Kalidindi et al (2015) that extracts from the leaves of annona squamosa with methanol, chloroform, solvents and water extract of leaves of annona squamosa shows activity of antifungal.

Leaf annona squamosa have properties against antifungal essential Alternaria alternate, Candida albicans, Fusarium solani, Microsporum canis and Aspergillus niger (Kalidindi et al., 2015). In addition, 16-hentriacontanone (palmitone) and 10-hydroxy-16-henriacontanone and quamocin A and G, and squamostatin A is an antifungal (Dang et al., 2011).

Some bacteria such as Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus and Campylobacter jejuni are sensitive to leaf extract (Dholvitayakhun el al., 2013). Leaf extract is also active against Streptococcus pneumoniae, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus epidermidis, Proteus species, Vibrio alginolyticus and (Padhi el al., 2011; Yusha'u et al., 2011; Pinto et al., 2017).

Annona squamosa seed exists on antibacterial by annotemoyin-1, annotemoyin-2, squamocin and cholesteryl Pseudomonus aeruginosa glukopiranosida against and Escherichia coli (Rahman et al., 2005). Bark extract annona squamosa with methanol, active against bacteria Bacillus coagulans and Escherichia coli (Kachhawa et al., 2012). O-methylarmepavine and C37 trihydroxy bistetrahydrofuran acetogenins was isolated from the leaves, which have an IC50 from 23.3 to 37.6 μg/ml against Leishmania chagasi (Vila-Nova et al., 2011).

k. Anti-oxidant Activity

Test results antioxidant activity of extracts of leaves of annona squamosa with IR, LC-MS flavones compounds obtained on the base of spectral data. In vitro, isolated compounds annona squamosa evaluated the activity of free radicals of various concentration with the method of DPPH free radical activity shows that significant compared to the synthetic antioxidants Butylated hydroxyl anisole (BHA) ( Chandrashekar et al., 201l).

Kalidindi et al (2015) isolates the glycosides, compounds, saponins, tannins, flavonoids, phenols, etc. with solvent methanol, chloroform, and water. The organic extracts from leaves of annona squamosa and water shows the activity of the free radical reducer by 1.1-diphenyl-2-picrylhydrazyl, nitric oxide, and hydrogen peroxide (Kalidindi et al., 2015; Shirwaikar et al., 2004; Baskar et al., 2007; El-Chaghaby et al., 2014; Chandrashekar and Kulkarni, 2011).

Giving oral 5,7,4'-trihydroxy 6.3'pronounced-O-dimethoxyflavone5-I-rhamnopyranoside (THDMF-Rha) significantly reduces oxidative stress cell (Panda and Kar, 2015). In addition, quercetin-3-O-glycosides having antioxidant activity with the intake of 15 mg/kg/day for 10 days significantly stir up the activity of catalase, superoxide dismutase and reduced glutathione (Panda and Kar, 2015).  The methanol extract and extract water from the pulp of the fruit annona squamosa have action silencer in DPPH, lipid concentration, nitric oxide, superoxide and hydroxyl radical (Jagtap and Bapat, 2012; Nandhakumar and Indumathi, 2013). Skin extract with ethanol also have efficacy as a reducer of free radicals (Pandey and Barve, 2011; Luzia and Jorge, 2012).

l. Anti-HIV Activity

Annona squamosa extract results there are new compounds by spectral analysis. 16β,17-dihydroxy-ent-kauran-19-oic acid showed significant activity against the HIV replication in cell H9 lymphocytes with EC50 values of 0.8 μg/mL (Saleem TS, 2008). 16beta-,17-dihidroksi-ent-kauran-19-oic acid isolated from various fruit annona squamosa have antiviral activity against HIV replication (Wu et al., 1996).

m. Cytotoxic Activity

The results of the seed extract there are two new compounds, evaluated for cytotoxic activity. Research results performed against human lung carcinoma HCT, (A-549), human breast carcinoma (MCF-7), and human prostate adenocarcinoma (PC-3) meet the standards of adriamycin with positive by the method MTT (Saha, 2011).

Anticancer potential of organic and water extract of leaves of annona squamosa by MTT (3-(4,5-dimethylthiazole-2il)-2,5-biphenyl tetrazolium bromide). Extract the rough (Zcd) and Ethyl acetate extract (ZE) found significant anticancer activity in human epidermoid carcinoma cell line KB-3-1 and colonic cancer cell line HCT-116 (Wang et al., 2014).

Fresh fruit annona squamosa have beneficial to cardiovascular risk. The acid Ent-kaur-16-en-19-oic and 16alpha-hydro-19-alent-acid kauran-17-acid on the stem annona squamosa have properties of platelet aggregation inhibition through antiplatelet (who et al., 2002) which had been utilized for atherosclerosis.

n. Anti-thyroid Activity

5,7,4'-trihydroxy 6.3'dimethoxy-5-O-flavone pronounced-Irhamnopyranoside (THDMF-Rha) was isolated from the leaves of annona squamosa have been known to be thyroid (Panda and Kar, 2015; OO and Khine, 2017).

o. Imunomodulator Activity

Bark contains annona squamosa Linuginosine (+)-Omethylarmepavine, Lanuginosine (+)-anomuricinem, Isocorydine and N-methyl-6,7-dimethoxyisoquinolone that can modulate the immune response (Soni et al., 2012). Esters of fatty acids, (+)-annonlipoxy inhibits the activity of lipooksigenase so that reduce the quantity of leucotrienes, and lipoxins (Sultana, 2008).

p. Vasorelaksan Activity

Cyclosquamosin B isolated from seeds of annona squamosa have vasorelaksan activity through inhibition of calcium release from extra cellular compartments (Morita el al., 2006). Evaluation of the therapeutic potential of cyclosquamosin-related advanced B needs to be investigated.

5. Conclusion

Annona Squamosa are generally known as Annona squamosa in the language of the United Kingdom. Some pharmacological activity such as anti-malaria, anti-tumour, anti-diabetic, anti-inflammatory, anti-microbial, anti-oxidant, anti-HIV, cytotoxic and a few other activities very important in human health. Therefore, further evaluation of potential pharmacological optimization of related techniques and new methods are indispensable.

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