Phytochemical and Pharmacological Profile
of Annona squamosa Linn:
A Review
NS
Jagtap1*, VP Nalamwar1, SS Khadabadi1 and AS
Pratapwar2
1Government
2S. N. Institute of Pharmacy, Pusad. Dist. Yavatmal (MS).
ABSTRACT
Acetogenin a different class of
secondary metabolites was found in various parts of Annona squamosa L. More than 20 different acetogenins were isolated from leaves, bark, fruits and
seeds. Cytotoxic and Insecticidal properties of Annona squamosa L.
were attributed to acetogenins. More than 13
different alkaloids, several terpenes, kauranes were isolated. Antibacterial activity was
attributed to terpenes and kauranes.
Seeds of Annona squamosa
yielded fixed oil containing hydroxyacids. Seeds were
found to contain anti-inflammatory cyclic peptides.
Many pharmacological
activities were experimentally reported on extracts of Annona squamosa L., these included Antitumour, Cytotoxic,
Anti-inflammatory, Analgesic, Antidiabetic,
Antioxidant, Larvicidal, Insecticidal, Molluscicidal, Licicidal,
Antibacterial, Nutritive, Antihtyroid.
Keywords: Annona squamosa, Phytochemical, Pharmacological studies.
INTRODUCTION
Herbal drugs play vital role in management of various
diseases like diabetis, arthritis, rhumatism and cancer. Herbal drugs also used
for erradication of microbial and parasitic infections caused to human being
and animals.
Cancer
is one of the disorders for which promising treatment option is not avilable
till date.Herbal drugs like Comptotheca, Vinca, Turmeric , Neem, are well known
for anticancer activity.
Now a days there is growing concern about ill effects
of allopathic anticancer drugs. Almost all of allopathic anticancer drugs have
immunosuppresive activity due to which patient become immunocompermised and
suffer from bacterial and fungal systemic infections. In many cases of deaths
of cancer patient this may be a reason.
Infestation
by insect parasites like mite, vermin, ticks is comman in man and
animals.Agricultural pests is major cause behind loss of fresh crop and stored
food grain. Some herbs like Garlic, Karanj, Camphor, Calamus, Adhatoda are well
known for insecticidal activity.
Many
synthetic insectisides are avilable like Malathion, DDT, Parathion, Permethrin,
Lindane etc. Ecological adverse effect and toxicity to human beings caused due
to use of synthetic insectisides is cause of concern.
Taxonomic
classification:
Kingdom: Planta
Division :
Magnoliophyta (Angiospermae)
Class
: Magnoliopsida
(Dicotyledons)
Subclass: Magnolidae
Order :
Magnoliales
Family :
Annonaceae
Genus :
Annona
Species :
Annona squamosa L.
Varietes : Sangareddy, Mammoth.
Synonym – Eng: Custard apple, Asm: Atlas, Ben: Ata, Mar:
Sitaphal, Mal: Sitapalam,Tel: Sitapandu, Tam: Attamaram, Hin: Sharifa, San: Gandgatrum, Ori: Seetapholo, Kan: Seethaphala.
Habit – Evergreen small tree 6-7 m. height.
Leaves – Simple, oblong, lanceolate,
arranged in opposite phyllotaxy.
Flowers - Green, freshy,
pubescent, solitary.
Fruits – Globus, cordate, aggregate, green segmented rind.
Seeds – Oblong, deep brown;
Bark – Grayish.
The tree bear flowers during Mar-Jul, fruits
mature during Oct-Dec. and harvested just before maturity.
Ayurvedic properties: –
Rasa- Mdhura, Guna-
Laghu, Virya- Sita, Vipaka- Madhura2.
PHYTOCHEMICAL
STUDIES:
Volatile constituents 1H cycloprop(e)azulene, germacrene D, bisabolene, bisabolene epoxide are reported from bark and leaves of Annona squamosa L.
the compounds were isolated and identified by GC, MS3. Volatile
constituents of essential oil from fruit are reported as α-pinene, sabinene and limonene
isolated and identified by GC-MS4. Essential oil obtained from the
leaves analysed by GC and GC-MS reported to contain monoterpenes, sesquiterpenes,
oxygenated sesquiterpenes, germacrene
D, β- elemene, bicyclogermacrene5.
Three kauranes (1)
(-) - ent-kaur-17-acetoxy, 19 oic acid, (2)
(-)-ent-kaur-17, 19 dioic acid, (3) 16α, 17
dihydroxy-ent-kauran-19-oic acid are reported from pericarp
of fruit. These compounds were isolated by bioactivity directed fractionation and
isolation technic6.
Seeds of Annona squamosa L. yield fixed oil major
constituent hydroxyacid reported as Isoricinoleic acid. The compound was isolated by using
silica gel column7.
Several alkaloids were isolated from leaves,
barks and roots of Annona squamosa L.
these include Anonaine, aporphine,
corydine, isocorydine, norcorydine, glaucine, norlaureline, roemerine, anolobine and reticuline. Samoquasine-A is a benzooxyquinazoline
alkaloid isolated from seeds, structure of samoquasine-A
was elucidated by spectroscopic and chemical methods8. Higenamine an isoquinoline
alkaloid of Annona squamosa L.
was found responsible for cardiac effect9. Acetogenine
a different class of secondary metabolites isolated from seeds and barks of Annona squamosa L.
It include squamocin, isosquamocin
squamostatin, squamostatin-A,
annonacin - A, I, II, annonacinone,
asimicin, neoannonin, annonastatin, squamone, bullatacin, bullatacinone, annonin- I, IV, VI, VIII, XIV10. Acetogenines are long chain aliphatic unsaturated 35 or 37
carbon containing compounds, they are substituted by –OH at various positions,
and they contain 1 or 2 tetrahydrofuran rings11.
According to hypothetical biosynthesis pathway acetogenins
arise from a polyketide pathway, Diene,
triene, trieneketone groups
undergo series of epoxidation and cyclization
reactions12. Annonacin, Annonacin-A, Annonastatin were
isolated from seeds of Annona squamosa L.
The relative configuration of tetrahydrofuran core
was established by C 13 NMR and H1 NMR13. The bis-tetrahydrofuran acetogenins Squamostatin B, C, D and E are reported to present in
petroleum ether extract of seeds. C-12/C-15 trans and C-20/C-23 trans
stereochemistry of the compounds was studied by C13 NMR14.
Squamosten-A from seeds was reported as monotetrahydrofuranic acetogenin
with a double bond in hydrocarbon chain15.
Cyclic peptides reported from seeds of Annona squamosa L.
include Cherimolacyclopeptide B.The
structures were studied by 2D NMR, electrospray
ionization and MS16.
PHARMACOLOGICAL
STUDIES:
Ayurvedic literature described Annona squamosa L.
fruits useful as tonic and nutritive, roots useful as purgative, leaves applied
as poultice on carbuncle17.
According to unani system of medicine Annona squamosa L. fruits enriches blood, seeds
are abortifacient
and produce ulcer in eye, and seeds kill headlice18.
Traditionally in
folklore medicines Annona squamosa L.
seeds are externally applied all over animal body to treat louse infestation19.
Paste of Annona squamosa L.
seeds and neem bark is used as Anthelminitic
by tribal people in Bihar20. Annona squamosa L. is known in folklore to have insecticidal
and vermicidal activities this was confirmed in
laboratory by taste with Drosophila melanogaster21.
Unripe fruit powder mixed with gram flour
and used to kill vermin22.
Powder of Annona squamosa L. seeds was soaked in water
for overnight and solution was obtained. The solution exhibited larvicidal activity against culex
larvae; mortality was reported by taking different concentrations of seed
powder ranging from 0.025% to 1.5 %23. Acetone extract of Annona squamosa L.
was reported as more toxic than pet-ether extract to Trogoderma granarium24. Pure acetogenins
(Squamocin, Squamocin-D)
isolated from seeds and pure alkaloids (-) Xylopine
isolated from leaves of Annona squamosa L.
was reported to have antifeedant activity and
insecticidal activity against tobacco caterpillar25. Ethanolic
extract of Annona squamosa L.
roots reported to have molluscicidal activity against
adults form and egg masses of Biomphalaria glabrata26.
Extract from leaves, bark and seeds of Annona squamosa L. were studied for molluscicidal
activity against snail Lymnaea acuminate. Seed extract reported to
have more potent activity compared to synthetic pesticides27. Pesticidal activity of combination of Annona squamosa L. and Pongamia glabra was studied against mosquitoes.
The activity was reported as comparable to Azadirachta indica against mosquitoes28. Methanolic and ethanolic extract of Annona squamosa L. reported to have larvicidal activity against mosquito larvae29.
Extract obtained from seeds of Annona squamosa L. reported to have residual toxicity against
Annoreticulin-9-one an acetogenin
isolated from bark of Annona squamosa L.
was studied for selective cytotoxicity against the
human pancreatic tumour cell line PACA-2. The
compound reported to have 10-100 times potent action than Adriamycin32.
Aqueous extract of defatted seeds of Annona squamosa L. was studied for antitumour
activity against AK-5 tumour cell line. Apoptosis was
reported to occur in tumour cells through generation
of free radicals. It was confirmed by DNA fragmentation, Annexin-V
staining and GSH level33. Dichloromethane and water extracts of deffated seeds of A. squamosa L. reported to induce apoptosis in MCF-7 and
K-562 cells. This was confirmed by nuclear condensation, DNA fragmentation and
reduced glutathione level34. Effect of oral administration of water
and ethanolic extract of Annona squamosa L.
leaves was studied on buccal pouch carcinogenesis in
hamster 7, 12 Dimethylebenzanthracene was used to
induce tumour. The study found that both extracts
have potent chemoprotective efficacy35. Etahnolic extract of Annona squamosa L. bark was studied for chemoprotective and anti-lipidperoxidative
efficacy in experimental oral carcinogenesis
in hamster. Painting with DMBA was used to induce oral squamous
cell carcinoma in hamster. Activity of ethanolic extract to prevent tumour formation is reported as more potent than water
extract36.
Hot water extract of Annona squamosa L. leaves was reported to have hypoglycemic
and antidiabetic activity in streptozotocin
induced diabetic rats and in alloxan induced diabetic
rabbits37. Aqueous and ethanolic extract of leaves of Annona squamosa L.
were administered orally to streptozotocin and nicotinamide induced Type-2 diabetic rats and studied for antidiabetic activity. Both extracts reported to have
significant antidiabetic potential38.
Effects of oral dose of aqueous extract of Annona squamosa L. leaves on glycogen level and
pancreatic TBARS level was studied, the findings supported antidiabetic
activity claim of Annona squamosa L39. Aqueous extract of Annona squamosa L. leaves was reported to have antioxidant and
hypolipidaemic activity in STZ induced diabetic rats.
Significant reduction in LDL, VLDL, cholesterol and increase in activity of
superoxide, dismutase and catalase was reported40.
Oral administration of Annona squamosa L.
aqueous extract to STZ induced diabetic rats was studied for beneficial effect
in preventing diabetic complication from lipid peroxidation41. Annona squamosa L.
fruit pulp administered orally studied for nutritive value improvement,
decrease in urine sugar, and increase in hemoglobin content in alloxan induced diabetic rabbits42. Ethanolic
extract of Annona squamosa L.
leaves administered orally for 10 days showed reduction in urine sugar in STZ
induced diabetics rats and alloxaon induced diabetic
rabbits43.
Anti-inflammatory activity of 16
β-17-dihydroxy-en-kauran-19oic acid isolated from stem was studied by
using isolated human neutrophils, the compound
reported to inhibit cytosolic calcium mobilization44.
Cyclosquamocin-D a cyclic peptide isolated from seeds
of Annona squamosa L.
was reported to inhibit cytokine production in macrophages45.
Aqueous and ethanolic extracts obtained from Annona squamosa L. leaves were studied for
analgesic and anti-inflammatory activity on carrageen and histamine were used
to induce oedema. Significant oedema
suppression was reported with water extract than ethanolic extract46.
Ent-kauranes isolated from stem of Annona squamosa L.
was reported to inhibit superoxide anion generation by human neutrophils47.
Ethanolic extract of Annona squamosa L.
was studied for antioxidant activity. The extract reported to show scavenging
of ABTS and DPPH radical cation48.
Annona squamosa L. extract was reported to have antifungal
activity against Colletotrichum capsici49
and antibacterial activity against Neisseria
gonorrhoeae50, E. coli and S. aureus6.
Annona squamosa L. seeds extract was reported to enhance
utilization of amylolytic,
lipolytic and proteolytic
enzymes in beetal gut (Pheropsophus
hilaris)51.
Annona squamosa L. seeds extract found to contain quercetin, the extract was studied for antithyroid
activity in animals52.
DISCUSSION:
Insecticidal and cyctotoxic
properties of Annona squamosa L.
are attributed to acetogenins. These acetogenins block mitochondrial respiration by inhibiting
NADH-cytochrome c oxidoreductase.
Annona squamosa L.
is an excellent antiparasite herb effective against
insects, molluscas, nematodes, larvae etc. This
property is of commercial interest and reflect wide scope to develop
multipurpose insecticidal formulations which can provide better alternative to
synthetic insecticides. SAR studied of acetogenins
with respect to antitumour property is need of hour,
this can provide new effective antitumour drug. No
doubt Annona squamosa L.
is a god gift for mankind to overcome insect menace and cancer.
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Received on 14.02.2009
Accepted on 11.05.2009
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Research Journal of Pharmacognosy and Phytochemistry. 1(3): Nov. – Dec 2009,
139-142