Annona squamosa seed extract in the regulation of hyperthyroidism and
lipid/​peroxidation in mice: Possible involvement of quercetin.

Panda S, Kar A.

Thyroid Research Laboratory, School of Life Sciences (Annex), Devi Ahilya
University, Vigyan Bhawan, Takhshila Campus, Khandwa Road, Indore 452017, Madhya
Pradesh, India.

Annona squamosa (Custard apple) seeds are generally thrown away as waste
materials. The extract of these seeds was evaluated for its possible
ameliorative effect in the regulation of hyperthyroidism in mouse model. Serum
triiodothyronine (T(3)), thyroxine (T(4)) concentrations, hepatic
glucose/​6/​phospatase (G/​6/​Pase) and 5'/​mono/​deiodinase (5'DI) activity were
considered as the end parameters of thyroid function. Simultaneously hepatic
lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT)
activities were investigated to observe its hepatotoxic effect, if any. L/​T(4)
administration (0.5mg/kg/d for 12 days, i.p.) increased the levels of serum T(3)
and T(4), activity of hepatic G/​6/​Pase, 5'DI and LPO with a parallel decrease in
SOD and CAT activities. However, simultaneous administration of the Annona seed
extract (200mg/kg) or quercetin (10mg/kg) to T(4)/​induced hyperthyroid animals
for 10 days, reversed all these effects indicating their potential in the
regulation of hyperthyroidism. Further, the seed extract did not increase, but
decreased the hepatic LPO suggesting its safe and antiperoxidative nature.
Quercetin also decreased hepatic LPO. When relative efficacy was compared with
that of propyl thiouracil (PTU), a standard antithyroidic drug, experimental
seed extract appeared to be more effective. Phytochemical analyses including
HPLC revealed the presence of quercetin in the seed extract and the results on
the effects of quercetin suggested the involvement of this phytochemical in the
mediation of antithyroidal activity of Annona squamosa seed extract.

PMID: 17291737 [PubMed /​ as supplied by publisher]

2: Phytochem Anal. 2007 Jan;18(1):7/​12.

Isolation and antimicrobial evaluation of isomeric hydroxy ketones in leaf
cuticular waxes of Annona squamosa.

Shanker KS, Kanjilal S, Rao BV, Kishore KH, Misra S, Prasad RB.

Lipid Science and Technology Division, Indian Institute of Chemical Technology,
Uppal Road, Hyderabad 500 007, India.

A novel natural compound, 11/​hydroxy/​16/​hentriacontanone, has been isolated from
the leaf cuticular wax of Annona squamosa along with its known isomer
10/​hydroxy/​16/​hentriacontanone in a ratio of 67:33. This isomeric mixture of
hydroxy ketones constituted together 16.5% of the total cuticular waxes. The new
compound was characterised using spectral and chromatographic techniques. The
major component was found to be 16/​hentriacontanone (palmitone), which
constituted up to 48% of the total cuticular wax, together with a homologous
series of hydrocarbons, fatty aldehydes, fatty alcohols, fatty acids and sterols
as minor components. The antimicrobial activity of the isomeric hydroxy ketones
was tested against selected Gram/​positive and Gram/​negative bacterial strains,
and also some selected fungal strains, and compared with palmitone. The
antibacterial activity of palmitone was significantly higher than that of the
isomeric hydroxy ketones, but their antifungal activities were comparable.

PMID: 17260693 [PubMed /​ indexed for MEDLINE]

3: Southeast Asian J Trop Med Public Health. 2006 May;37(3):532/​5.

Anti/​head lice effect of Annona squamosa seeds.

Intaranongpai J, Chavasiri W, Gritsanapan W.

Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok,
Thailand.

The present study focused on the separation and identification of the active
compounds against head lice from the hexane extract of Annona squamosa L seed.
Chromatographic and spectroscopic techniques revealed that two major compounds
of the hexane seed extract were oleic acid and triglyceride with one oleate
ester. The yields of these compounds were 13.25% and 7.74% dry weight,
respectively. The compounds were tested in vitro against head lice, comparing to
the crude hexane extract of the seed. The triglyceride with one oleate ester and
the crude hexane extract diluted with coconut oil 1:1. These compounds were
found to kill all tested head lice in 49, 11 and 30 minutes, respectively. The
triglyceride ester can be used as a marker for quantitative analysis of the
active compound for quality control of the raw material A. squamosa seed and its
extract. This first finding will be useful for quality assessment and the
chemical stability of the antihead lice preparation from this plant.

PMID: 17120975 [PubMed /​ indexed for MEDLINE]

4: J Ethnobiol Ethnomedicine. 2006 Oct 13;2:45.

Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes
mellitus.

Lans CA.

BCICS, University of Victoria, British Columbia, V8W 2Y2, Canada.
cher2lans@netscape.net.

ABSTRACT: BACKGROUND: This paper is based on ethnobotanical interviews conducted
from 1996/​2000 in Trinidad and Tobago with thirty male and female respondents.
METHODS: A non/​experimental validation was conducted on the plants used for
urinary problems and diabetes mellitus: This is a preliminary step to establish
that the plants used are safe or effective, to help direct clinical trials, and
to inform Caribbean physicians of the plants' known properties to avoid
counter/​prescribing. RESULTS: The following plants are used to treat diabetes:
Antigonon leptopus, Bidens alba, Bidens pilosa, Bixa orellana, Bontia
daphnoides, Carica papaya, Catharanthus roseus, Cocos nucifera, Gomphrena
globosa, Laportea aestuans, Momordica charantia, Morus alba, Phyllanthus
urinaria and Spiranthes acaulis. Apium graviolens is used as a heart tonic and
for low blood pressure. Bixa orellana, Bontia daphnoides, Cuscuta americana and
Gomphrena globosa are used for jaundice. The following plants are used for
hypertension: Aloe vera, Annona muricata, Artocarpus altilis, Bixa orellana,
Bidens alba, Bidens pilosa, Bonta daphnoides, Carica papaya, Cecropia peltata,
Citrus paradisi, Cola nitida, Crescentia cujete, Gomphrena globosa, Hibiscus
sabdariffa, Kalanchoe pinnata, Morus alba, Nopalea cochinellifera, Ocimum
campechianum, Passiflora quadrangularis, Persea americana and Tamarindus
indicus.The plants used for kidney problems are Theobroma cacao, Chamaesyce
hirta, Flemingia strobilifera, Peperomia rotundifolia, Petiveria alliacea,
Nopalea cochinellifera, Apium graveolens, Cynodon dactylon, Eleusine indica,
Gomphrena globosa, Pityrogramma calomelanos and Vetiveria zizanioides. Plants
are also used for gall stones and for cooling. CONCLUSION: Chamaesyce hirta,
Cissus verticillata, Kalanchoe pinnata, Peperomia spp., Portulaca oleraceae,
Scoparia dulcis, and Zea mays have sufficient evidence to support their
traditional use for urinary problems, "cooling" and high cholesterol.Eggplant
extract as a hypocholesterolemic agent has some support but needs more study.
The plants used for hypertension, jaundice and diabetes that may be safe and
justify more formal evaluation are Annona squamosa, Aloe vera, Apium graveolens,
Bidens alba, Carica papaya, Catharanthus roseus, Cecropia peltata, Citrus
paradisi, Hibsicus sabdariffa, Momordica charantia, Morus alba, Persea
americana, Phyllanthus urinaria, Tamarindus indicus and Tournefortia
hirsutissima. Several of the plants are used for more than one condition and
further trials should take this into account.

PMID: 17040567 [PubMed /​ in process]

5: Singapore Med J. 2006 Aug;47(8):670/​5.

Antidiabetic and antioxidant activity of Annona squamosa extract in
streptozotocin/​induced diabetic rats.

Kaleem M, Asif M, Ahmed QU, Bano B.

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University,
Aligarh 202002, India. kaleem_biochem@yahoo.com

INTRODUCTION: The aim of the study is to analyse the antioxidant effect of oral
administration of aqueous extract of Annona squamosa (A. squamosa) leaf on blood
glucose, haemoglobin, glycosylated haemoglobin, plasma insulin, antioxidant
enzymes and lipid peroxidation in liver and kidney to streptozotocin
(STZ)/​induced diabetic rats. METHODS: Aqueous extract of A. squamosa on blood
glucose, haemoglobin, glycosylated haemoglobin, plasma insulin, serum lipid and
the levels of lipid peroxides and antioxidant enzymes, such as catalase,
superoxide dismutase, glutathione peroxidase and reduced glutathione, were
examined in the liver and kidney tissues of control and experimental groups.
RESULTS: Oral administration of A. squamosa aqueous extract to diabetic rats for
30 days significantly reduced the levels of blood glucose, lipids and lipid
peroxidation, but increased the activities of plasma insulin and antioxidant
enzymes, like catalase, superoxide dismutase, reduced glutathione and
glutathione peroxidase. CONCLUSION: The A. squamosa aqueous extract
supplementation is useful in controlling the blood glucose level, improves the
plasma insulin, lipid metabolism and is beneficial in preventing diabetic
complications from lipid peroxidation and antioxidant systems in experimental
diabetic rats; therefore, it could be useful for prevention or early treatment
of diabetes mellitus.

PMID: 16865205 [PubMed /​ indexed for MEDLINE]

6: Bioorg Med Chem Lett. 2006 Sep 1;16(17):4609/​11. Epub 2006 Jun 19.

Vasorelaxant activity of cyclic peptide, cyclosquamosin B, from Annona squamosa.

Morita H, Iizuka T, Choo CY, Chan KL, Takeya K, Kobayashi J.

Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa/​ku, Tokyo,
Japan. moritah@hoshi.ac.jp

A cyclic octapeptide, cyclosquamosin B (2), isolated from the seeds of Annona
squamosa showed a vasorelaxant effect on rat aorta. It showed a slow relaxation
activity against norepinephrine (NE)/​induced contractions of rat aorta
with/without endothelium. It 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 2 might be attributed mainly to
inhibition of calcium influx from extracellular space through voltage/​dependent
calcium channels.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16784851 [PubMed /​ indexed for MEDLINE]

7: Nat Prod Res. 2006 Jul 10;20(8):754/​7.

Major volatile constituents of Annona squamosa L. bark.

Chavan MJ, Shinde DB, Nirmal SA.

Department of Pharmacognosy, Pravara Rural college of Pharmacy, Pravaranagar,
A/P/​Loni 413736, Tal/​Rahata, Ahmednagar district, Maharashtra, India.

The volatile constituents of Annona squamosa L. bark were identified from the
essential oil obtained by steam distillation and studied by GC/MS. Six major
components were identified as 1H/​Cycloprop(e)azulene (3.46%), germacrene D
(11.44%), bisabolene (4.48%), caryophyllene oxide (29.38%), bisabolene epoxide
(3.64%) and kaur/​16/​ene (19.13%). The oil was also screened for its
antimicrobial activity, which exhibited a significant antimicrobial activity
against Bacillus subtilis and Staphylococcus aureus.

PMID: 16753909 [PubMed /​ indexed for MEDLINE]

8: J Vector Borne Dis. 2005 Dec;42(4):159/​63.

Comparative efficacy of Annona squamosa Linn. and Pongamia glabra Vent. to
Azadirachta indica A. juss against mosquitoes.

George S, Vincent S.

Department of Microbiology, Asan Memorial College, Chennai, India.

PMID: 16457387 [PubMed /​ indexed for MEDLINE]

9: Planta Med. 2005 Oct;71(10):904/​9.

An anti/​inflammatory ent/​kaurane from the stems of Annona squamosa that inhibits
various human neutrophil functions.

Yeh SH, Chang FR, Wu YC, Yang YL, Zhuo SK, Hwang TL.

Graduate Institute of Natural Products, College of Medicine, Chang Gung
University, 259 Wen/​Hwa 1st Road, Kweishan 333, Taoyuan, Taiwan, ROC.

We have previously shown that 11 ent/​kauranes isolated from the stems of Annona
squamosa exhibited immunomodulating effects in leukocytes. In this study, a
cellular model using isolated human neutrophils, which are important in the
pathogenesis of rheumatoid arthritis, ischemia/​reperfusion injury, chronic
obstructive pulmonary disease, asthma and other inflammatory diseases, was
established in order to elucidate the anti/​inflammatory functions of
16beta,17/​dihydroxy/​ent/​kauran/​19/​oic acid (1). Reactive oxygen species (ROS)
and granule proteases produced by neutrophils contribute to the pathogenesis of
inflammatory diseases. Compound 1 inhibited the generation of superoxide anion,
the formation of ROS, and the release of elastase in
formyl/​L/​methionyl/​L/​leucyl/​L/​phenylalanine (FMLP)/​activated human neutrophils
in a concentration/​dependent manner with IC (50) values of 3.95 +//​ 0.68, 12.20
+//​ 2.16, and 12.52 +//​ 2.26 microM, respectively. The anti/​inflammatory actions
were not attributable to cytotoxicity because incubation of the neutrophils with
1 did not result in lactate dehydrogenase release. Compound 1 did not display
antioxidant or superoxide anion/​scavenging activity. Furthermore, neither
subcellular NADPH oxidase activity nor cAMP/​dependent pathways were altered by
1. Compound 1 significantly inhibited rapid calcium release from internal
calcium stores induced by FMLP but not by thapsigargin. In summary, the
presented results indicate that the inhibitory effects of 1 on respiratory burst
and degranulation of human neutrophils are through the inhibition of cytosolic
calcium mobilization, but not via the cAMP/​dependent pathways.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16254820 [PubMed /​ indexed for MEDLINE]

10: Ann Nutr Metab. 2005 Nov/​Dec;49(6):407/​13. Epub 2005 Oct 17.

Nutritional and hypoglycemic effect of fruit pulp of Annona squamosa in normal
healthy and alloxan/​induced diabetic rabbits.

Gupta RK, Kesari AN, Watal G, Murthy PS, Chandra R, Tandon V.

Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, India.

The nutritive value of the pulp of the edible fruit of Annona squamosa and its
effect on various biochemical parameters has been assessed in normal and
alloxan/​induced diabetic rats. Different doses (2.5, 5.0, 10.0 g/kg b.w.) of
fresh fruit pulp of A. squamosa were given to the three groups each of normal
healthy and diabetic rabbits orally daily for 1 month. There was a control group
of normal as well as diabetic animals which did not receive fruit pulp. Protein
efficiency ratio (PER), digestibility coefficient (DC), biological value (BV)
and net protein utilization (NPU) were calculated and improvement in the
nutritional level was studied by comparing with the control group. Effect of the
fruit pulp was also studied on various biochemical parameters, namely fasting
blood glucose (FBG), total cholesterol (TCH), HDL/​cholesterol, triglyceride
(TG), total protein (TPR), alkaline phosphatase (ALKP), serum glutamate
oxaloacetate and pyruvate transaminases (SGOT and SGPT), serum creatinine (CRTN)
and serum bilirubin (BIL). Protein and glucose in urine were also estimated.
Total hemoglobin and glycohemoglobin (HbAc) were estimated in blood before and
after 1 month of feeding fruit pulp. Fruit pulp increased the net protein
utilization by 29.3 in normal healthy rabbits with 10 g/kg b.w. and 34.1 in
induced diabetic (induced by alloxan) animals with 5 g/kg b.w. of the fruit pulp
feeding when compared with the control group of rabbits (p < 0.001). Feeding
fruit pulp with the same amount increased the total hemoglobin content by 21.0%
in normal rabbits and 10.8% in diabetic rabbits. Fruit pulp also reduced the
total cholesterol level by 45/​46% in normal and 32.4% in diabetic animals with
increased HDL/​cholesterol. Feeding pulp improved the liver function in normal as
well as diabetic rabbit as shown by reduction in the serum SGOT, SGPT, ALKP and
bilirubin levels. The optimal improvement in nutritive value of normal animals
was found with 5.0/​10.0 g/kg b.w. of the fruit pulp feeding, while in diabetic
animals it was 2.5/​5.0 g/kg b.w. In the diabetic animals pulp feeding between
2.5 and 5.0 g/kg b.w. showed improvement in the glucose tolerance. Further, 5
g/kg b.w. of fruit pulp brought down urine sugar, urine protein and
glycohemoglobin in diabetic rabbits. Feeding pulp had increased utilization of
dietary protein, body weight as well as the ratio of gain in body weight per
gram of protein consumed. It had a protective effect on liver and heart as
indicated by reduction in the SGOT, SGPT, ALKP and serum bilirubin levels.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16230844 [PubMed /​ indexed for MEDLINE]

11: J Econ Entomol. 2005 Aug;98(4):1193/​201.

Rain forest provides pollinating beetles for atemoya crops.

Blanche R, Cunningham SA.

CSIRO Entomology, Tropical Forest Research Centre, P.O. Box 780, Atherton,
Queensland 4883, Australia.

Small beetles, usually species of Nitidulidae, are the natural pollinators of
atemoya (Annona squamosa L. x A. cherimola Mill. hybrids; custard apple) flowers
but commercial atemoya growers often need to carry out labor/​intensive hand
pollination to produce enough high/​quality fruit. Because Australian rain forest
has plant species in the same family as atemoya (Annonaceae) and because many
rain forest plants are beetle pollinated, we set out to discover whether
tropical rain forest in far north Queensland harbors beetles that could provide
this ecosystem service for atemoya crops. Orchards were chosen along a gradient
of increasing distance from tropical rain forest (0.1/​24 km). We sampled 100
flowers from each of nine atemoya orchards and determined the identity and
abundance of insects within each flower. To assess the amount of pollination due
to insects, we bagged six flowers per tree and left another six flowers per tree
accessible to insects on 10 trees at an orchard near rain forest. Results
indicated that atemoya orchards < or = 0.5 km from rain forest were
predominantly visited by five previously unrecognized native beetle pollinators
that are likely to originate in tropical rain forest. These native beetles
occurred reliably enough in crops near rain forest to have a positive effect on
the quantity of fruit produced but their contribution was not great enough to
satisfy commercial production needs. Management changes, aimed at increasing
native beetle abundance in crops, are required before these beetles could
eliminate the need for growers to hand pollinate atemoya flowers. Appreciation
of the value of this resource is necessary if we are to develop landscapes that
both conserve native biodiversity and support agricultural production.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16156571 [PubMed /​ indexed for MEDLINE]

12: Fitoterapia. 2005 Jul;76(5):484/​9.

Antimicrobial and cytotoxic constituents from the seeds of Annona squamosa.

Mukhlesur Rahman M, Parvin S, Ekramul Haque M, Ekramul Islam M, Mosaddik MA.

Phytochemistry Research Laboratory, Department of Pharmacy, University of
Rajshahi, Rajshahi/​6205, Bangladesh. mukhlesurrah@yahoo.co.uk

Annotemoyin/​1, Annotemoyin/​2, squamocin and cholesteryl glucopyranoside were
isolated from the seeds of Annona squamosa. These compounds and plant extracts
showed remarkable antimicrobial and cytotoxic activities.

PMID: 15964712 [PubMed /​ indexed for MEDLINE]

13: J Biosci. 2005 Mar;30(2):237/​44.

Differential cytotoxic effects of Annona squamosa seed extracts on human tumour
cell lines: role of reactive oxygen species and glutathione.

Pardhasaradhi BV, Reddy M, Ali AM, Kumari AL, Khar A.

Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.

Annonaceous acetogenins are a new class of compounds that have been reported to
have potent pesticidal, parasiticidal, anti/​microbial, cell growth inhibitory
activities. In this study, organic and aqueous extracts from the defatted seeds
of Annona squamosa (custard apple) were tested on different human tumour cell
lines for antitumoural activity. While organic and aqueous extracts induced
apoptosis in MCF/​7 and K/​562 cells, they failed to do so in COLO/​205 cells.
Treatment of MCF/​7 and K/​562 cells with organic and aqueous extracts resulted in
nuclear condensation, DNA fragmentation, induction of reactive oxygen species
(ROS) generation and reduced intracellular glutathione levels. In addition
downregulation of Bcl/​2 and PS externalization by Annexin/​V staining suggested
induction of apoptosis in MCF/​7 and K/​562 cells by both the extracts through
oxidative stress. On the contrary, COLO/​205 cells showed only PS externalization
but no change in ROS and glutathione levels. These observations suggest that the
induction of apoptosis by A. squamosa extracts can be selective for certain
types of cancerous cells.

Publication Types:
Comparative Study
Research Support, Non/​U.S. Gov't

PMID: 15886460 [PubMed /​ indexed for MEDLINE]

14: Yao Xue Xue Bao. 2005 Feb;40(2):153/​8.

[Chemical constituents from the seeds of Annona squamosa]

[Article in Chinese]

Yu JG, Luo XZ, Sun L, Li DY, Huang WH, Liu CY.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences
and Peking Union Medical College, Beijing 100094, China. yujingguang@163.com

AIM: To study the antitumor active constituents of the seeds from Annona
squamosa L. (Annonaceae). METHODS: Various chromatographic techniques were used
to isolate and purify the constituents. Their physico/​chemical properties and
spectral data were determined to elucidate the structures. RESULTS: Eleven
compounds were isolated and identified as annonaceous acetogenins: squamocenin
(1), annotemoyin/​2 (2), reticulatain/​2 (3), squamocin/​I (4), squamocin/​B (5),
squamocin (6), motrilin (7), squamostatin/​D (8), squamostatin/​E (9),
cherimolin/​1 (10), cherimolin/​2 (11) from the ethyl alcohol extract of A.
squamosa L. CONCLUSION: Squamocenin (1) is a new acetogenin. Annotemoyin/​2 (2)
and reticulatain/​2 (3) were isolated from this plant for the first time.

Publication Types:
English Abstract
Research Support, Non/​U.S. Gov't

PMID: 15875673 [PubMed /​ indexed for MEDLINE]

15: J Ethnopharmacol. 2005 May 13;99(1):75/​81.

Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona
squamosa L. in experimental animals.

Gupta RK, Kesari AN, Murthy PS, Chandra R, Tandon V, Watal G.

Alternative Therapeutics Unit, Drug Development Division, Medicinal Research
Laboratary, Department of Chemistry, University of Allahabad, Allahabad/​211002,
U.P., India.

The ethanolic extract of Annona squamosa L. (Annonaceae) leaves was administered
orally at different doses to normal as well as streptozotocin (STZ)/​induced
diabetic rats and alloxan/​induced diabetic rabbits. The dose of 350 mg/kg body
weight (bw) reduced the fasting blood glucose (FBG) level by 6.0% within 1 h,
whereas, the peak blood glucose at 1 h during glucose tolerance test (GTT) was
reduced by 17.1% in normal rats. The same dose of ethanolic extract reduced FBG
by 26.8% and improved glucose tolerance by 38.5 and 40.6% at 1 and 2 h,
respectively, during GTT in alloxan/​induced diabetic rabbits. In STZ/​diabetic
rats, a fall of 13.0% in FBG and an improvement in glucose tolerance by 37.2 and
60.6% at 1 and 2 h, respectively, was observed during GTT. The dose of 350 mg/kg
bw 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.
Treatment of severely/​diabetic rabbits for 15 days with a dose of 350 mg/kg of
extract reduce FBG by 52.7% and urine sugar by 75%. It brought about fall in the
level of total cholesterol (TC) by 49.3% with increase of 30.3% in high/​density
lipoprotein (HDL) and decrease of 71.9 and 28.7% in low/​density lipoprotein
(LDL) and triglycerides (TG) levels, respectively.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15848023 [PubMed /​ indexed for MEDLINE]

16: Sex Transm Dis. 2005 Feb;32(2):106/​11.

Preliminary studies on activity of Ocimum sanctum, Drynaria quercifolia, and
Annona squamosa against Neisseria gonorrhoeae.

Shokeen P, Ray K, Bala M, Tandon V.

Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi,
India.

BACKGROUND: Despite the progressive increase of antimicrobial resistance of
Neisseria gonorrhoeae worldwide, there are limited reports of alternative
remedies from plants. GOAL: The aim of the current study was to screen 3 plants,
Ocimum sanctum, Drynaria quercifolia, and Annona squamosa, for activity against
Neisseria gonorrhoeae. STUDY: By disc diffusion method, extracts of these 3
plants were screened for activity against Neisseria gonorrhoeae; their
antimicrobial activity was calculated as percentage inhibition and compared with
penicillin and ciprofloxacin. RESULTS: The extracts of all 3 plants caused
inhibition of Neisseria gonorrhoeae clinical isolates and World Health
Organization (WHO) strains, more so than the multidrug resistant Neisseria
gonorrhoeae. CONCLUSION: Neisseria gonorrhoeae clinical isolates and WHO strains
were sensitive to extracts of Ocimum sanctum, Drynaria quercifolia, and Annona
squamosa. This motivates us to isolate the active component/second from the 3
plants.

PMID: 15668617 [PubMed /​ indexed for MEDLINE]

17: Pest Manag Sci. 2005 Feb;61(2):204/​8.

Effect of binary combination of some plant/​derived molluscicides with MGK/​264 or
piperonyl butoxide on the reproduction of the snail Lymnaea acuminata.

Singh P, Singh VK, Singh DK.

Department of Zoology, DDU Gorakhpur University, Gorakhpur/​273 009, India.

The effects of sub/​lethal treatments (20 and 60% of 24/​h LC(50)) with
plant/​derived molluscicides Annona squamosa, acetogenins, Argemone mexicana seed
and protopine, in combination (1 + 5) with MGK/​264 (ENT 8184) or piperonyl
butoxide on the reproduction of Lymnaea acuminata has been studied. The
plant/​derived molluscicides and their active molluscicidal components, protopine
and acetogenins, in combination with ENT 8184 or piperonyl butoxide caused a
significant reduction in the fecundity, hatchability and survival of young
snails. Combination of A squamosa seed powder with piperonyl butoxide was very
effective as it caused a complete arrest of snail fecundity within 24 h of
treatment. Removal of the snails to fresh water after the 96/​h treatments caused
a significant recovery in the fecundity of L acuminata. Copyright (c) 2005
Society of Chemical Industry.

PMID: 15619718 [PubMed /​ indexed for MEDLINE]

18: Indian J Exp Biol. 2004 Aug;42(8):803/​7.

In vitro antioxidant studies of Annona squamosa Linn. leaves.

Shirwaikar A, Rajendran K, Kumar CD.

Department of Pharmacognosy, College of Pharmaceutical Sciences, Manipal 576
104, India. annieshirwaikar@yahoo.com

The free radical scavenging potential of the leaves of A. squamosa 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 therapeutic applications of the plant in
the indigenous system of medicine, augmenting its therapeutic value.

Publication Types:
In Vitro

PMID: 15573531 [PubMed /​ indexed for MEDLINE]

19: Parasitology. 2004 Aug;129(Pt 2):245/​53.

Evaluation of anthelmintic properties of some plants used as livestock dewormers
against Haemonchus contortus infections in sheep.

Githiori JB, Hoglund J, Waller PJ, Baker RL.

International Livestock Research Institute, Nairobi, Kenya. J.Githiori@cgiar.org

Gastrointestinal helminth infections remain a major constraint to livestock
production globally. This study evaluated anthelmintic efficacy of 7 plants used
as dewormers by farmers and pastoralists in Kenya. Thus 3 commercial
anthelmintics and 7 plant preparations were tested in lambs infected with 5000
or 3000 L3 Haemonchus contortus in 4 experiments. In the first experiment,
ivermectin, levamisole and albendazole were tested in 46 lambs. Seven plant
preparations of Hagenia abyssinica, Olea europaea var. africana, Annona
squamosa, Ananas comosus, Dodonea angustifolia, Hildebrandtia sepalosa and
Azadirachta indica were tested in 151 lambs in 3 experiments. All 3
anthelminitics were highly effective in reducing faecal egg counts (FEC) and
total worm counts (TWC) in lambs. Plant preparations had varying levels of crude
proteins from 2.6% for O. europaea to 18.4% for A. indica. Compared with
controls, no significant reductions in FEC were observed for any of the treated
groups either 2 or 3 weeks post/​treatment. Lambs treated with A. squamosa and A.
comosus were slaughtered 4 weeks post/​treatment. No significant differences were
observed in mean TWC or number of eggs per female worm between treated animals
and the controls. No significant improvements in weight gain were observed in
treated lambs.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15376783 [PubMed /​ indexed for MEDLINE]

20: Arch Environ Contam Toxicol. 2004 May;46(4):470/​7.

Effect of herbal molluscicides and their combinations on the reproduction of the
snail Lymnaea acuminata.

Singh A, Singh DK.

Department of Zoology, DDU Gorakhpur University, India.

Effects of sublethal treatment (20 and 60% of LC50/24 h) of the plant/​derived
molluscicides Annona squamosa Linn. and Lawsonia inermis Linn. and their
combinations with other herbal molluscicides, such as Cedrus deodara Roxb,
Azadirachta indica A. Juss, bulb powder of Allium sativum Linn. and Polianthes
tuberosa Linn., and oleoresin of Zingiber officinale Rosc., and acetogenins
extracted from the seeds of A. squamosa Linn., on the reproduction of the snail
Lymnaea acuminata have been studied. It was observed that the plant/​derived
molluscicides singly and in binary combinations with other herbal molluscicides
and the extracted acetogenins caused a significant reduction in the fecundity,
hatchability, and survival of young snails. Withdrawal of the snails to fresh
water after the above treatment caused a significant recovery in the fecundity
of the snail Lymnaea acuminata. Twenty/​four/​hour sublethal treatment with the
acetogenins caused a maximum reduction in the protein, amino acid, DNA, and RNA
in the ovotestis of treated Lymnaea acuminata.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15253044 [PubMed /​ indexed for MEDLINE]

21: Planta Med. 2004 Mar;70(3):256/​8.

Inhibitory effects of ent/​kauranes from the stems of Annona squamosa on
superoxide anion generation by human neutrophils.

Yang YL, Chang FR, Hwang TL, Chang WT, Wu YC.

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung,
Taiwan, R.O.C.

Eleven ent/​kauranes, isolated from the fresh stems of Annona squamosa L.
(Annonaceae), were subjected to assays on the generation of superoxide anion
(O2./​/​) by human neutrophils. Except for ent/​kaur/​16/​en/​19/​oic acid,
16beta,17/​dihydroxy/​ ent/​kauran/​19/​al, and 16alpha,17/​dihydroxy
/​ent/​kauran/​19/​al, all ent/​kauranes showed significant inhibitory effect on
O2./​/​ generation in response to formyl/​ L/​methionyl/​ L/​leucyl/​ L/​phenylalanine
(fMLP/CB). In contrast, phorbol myristate acetate (PMA)/​induced O2./​/​ generation
was not suppressed by any ent/​kauranes. Especially, ent/​kaur/​16/​en/​19/​oic acid
could significantly increase O2./​/​ production. The structure/​activity
relationship of these compounds is also discussed herein. Furthermore, the
effect of ent/​kauranes on nitric oxide generation by NR8383 macrophages in
response to lipopolysaccharide (LPS) was examined. None of the compounds showed
an inhibitory effect on nitric oxide generation.

Publication Types:
Letter
Research Support, Non/​U.S. Gov't

PMID: 15114504 [PubMed /​ indexed for MEDLINE]

22: J Ethnopharmacol. 2004 Mar;91(1):171/​5.

Antidiabetic activity of aqueous leaf extract of Annona squamosa in
streptozotocin/​nicotinamide type 2 diabetic rats.

Shirwaikar A, Rajendran K, Dinesh Kumar C, Bodla R.

Department of Pharmacognosy, College of Pharmaceutical Sciences, Manipal 576119,
India. annieshirwaikar@yahoo.com

The claim by some tribal populations in parts of Northern India that the young
leaves of the custard apple tree, Annona squamosa L. (Annonaceae) has
antidiabetic properties was investigated. Diabetes mellitus was induced with
streptozotocin/​nicotinamide and graded doses of the aqueous leaf extracts were
then administered in drinking water to normal and experimental diabetic rats for
12 days. Fasting plasma glucose levels, serum insulin levels, serum lipid
profiles and changes in body weight were evaluated in normal rats while liver
glycogen levels and pancreatic TBARS levels were evaluated additionally in
diabetic rats. The diabetic groups treated with the aqueous leaf extract were
compared with standard glibenclamide. The findings of the study support the
antidiabetic claims of Annona squamosa.

PMID: 15036485 [PubMed /​ indexed for MEDLINE]

23: Indian J Exp Biol. 2002 Mar;40(3):363/​5.

Evaluation of mosquitocidal activity of Annona squamosa leaves against filarial
vector mosquito, Culex quinquefasciatus Say.

Jaswanth A, Ramanathan P, Ruckmani K.

Department of Pharmacology, Periyar College of Pharmaceutical Sciences for
Girls, Tiruchirappalli, 620 021, India. ajaswanth01@yahoo.com

Methanolic extract of leaves of A. squamosa was tested for mosquitocidal effect
against C. quinquefasciatus. A liquid mosquito insecticide formulation was
prepared with the extract (1, 3 and 5 %w/w) using deodorized kerosene as solvent
and investigated for its knock/​down and 24 hr mortality. The extract formulation
produced dose dependent activity, exhibited significantly shorter knock down
KD50 and KD90 values and produced significant mortality. The results suggest the
potential mosquitocidal effect of A. squamosa on C. quinquefasciatus.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 12635713 [PubMed /​ indexed for MEDLINE]

24: Phytomedicine. 2002 Oct;9(7):667/​72.

Effects of Annona squamosa extract on early pregnancy in rats.

Damasceno DC, Volpato GT, Sartori TC, Rodrigues PF, Perin EA, Calderon IM, Rudge
MV.

Experimental Laboratory of Obstetrics, Department of Gynecology and Obstetrics
of School of Human Medicine of Botucatu/​UNESP, Sao Paulo State, Brazil.
decaito@bol.com.br

Annona squamosa Linn., family Annonaceae, is said to show varied medicinal
effects, including insecticide, antiovulatory and abortifacient. The purpose of
present study was to investigate if A. squamosa seed aqueous extract, in doses
higher than that popularly used to provoke abortion, interferes with
reproductive performance, and to correlate the ingestion of this extract with
possible alterations in rat embryonic implantation. Doses of 300 mg/kg (Treated
Group I, n = 17) and 600 mg/kg (Treated Group II, n = 12) body wt. were
administered by gavage, during days 1 to 5 of pregnancy (preimplantation
period). The control group (n = 13) received water in the same manner, during
the same period for comparison with experimental groups. The animals were
euthanized on day 10 of pregnancy. Treatment of dams during the preimplantation
period showed no signs of toxicity, and no alteration in the corpora lutea,
implantations and embryo in terms of development numbers. The percentage of
preimplantation and postimplantation losses in treated groups I and II did not
differ from those of control. Treatment with aqueous extract of A. squamosa
seeds caused no morphological change in the endometrium. The absence of
morphological alterations in uterine epithelial cells in treated groups I and II
permitted a viable embryonic implantation, as verified by the number of embryos
in development at day 10 of pregnancy. Thus, A. squamosa seed aqueous extract
did not interfere with the reproductive performance of pregnant rats.

PMID: 12487333 [PubMed /​ indexed for MEDLINE]

25: Phytochemistry. 2002 Dec;61(8):999/​1004.

Squamocin/​O(1) and squamocin/​O(2), new adjacent bis/​tetrahydrofuran acetogenins
from the seeds of Annona squamosa.

Araya H, Sahai M, Singh S, Singh AK, Yoshida M, Hara N, Fujimoto Y.

National Institute for Agro/​Environmental Sciences, Kan/​nondai, Tsukuba, Ibaraki
305/​8604, Japan.

Two bis/​tetrahydrofuran acetogenins, squamocin/​O(1) (1) and squamocin/​O(2) (2),
were isolated from a MeOH extract of seeds of Annona squamosa L. Their
structures were determined by spectral means including precursor/​ion scanning
mass spectral analysis for their aminal derivatives. The configurations at the
oxymethine chiral centers were assigned as 12R,15R,16R,19R,20R,23R,24S,28S,36S
for 1 and 12S,15R,16R,19R,20R,23R,24S, 28S,36S for 2, based on 1H NMR analysis
of their Mosher's ester derivatives and CD data.

PMID: 12453534 [PubMed /​ indexed for MEDLINE]

26: J Nat Prod. 2002 Oct;65(10):1462/​7.

New ent/​kaurane diterpenoids with anti/​platelet aggregation activity from Annona
squamosa.

Yang YL, Chang FR, Wu CC, Wang WY, Wu YC.

Graduate Institute of Natural Products, Kaohsiung Medical University, Taiwan,
Republic of China.

A phytochemical investigation on the stems of Annona squamosa led to the
isolation of six new ent/​kaurane diterpenoids, annomosin A
(16beta/​hydroxy/​19/​al/​ent/​kauran/​17/​yl 16beta/​hydro/​19/​al/​ent/​kauran/​17/​oate)
(1), annosquamosin C (16alpha/​hydro/​17/​hydroxy/​19/​nor/​ent/​kauran/​4alpha/​ol) (2),
annosquamosin D (16beta/​acetoxy/​17/​hydroxy/​19/​nor/​ent/​kauran/​4alpha/​ol) (3),
annosquamosin E (16beta/​hydroxy/​17/​acetoxy/​19/​nor/​ent/​kauran/​4alpha/​formate)
(4), annosquamosin F
(16beta/​hydroxy/​17/​acetoxy/​18/​nor/​ent/​kauran/​4beta/​hydroperoxide) (5), and
annosquamosin G (16beta,17/​dihydroxy/​18/​nor/​ent/​kauran/​4beta/​hydroperoxide) (6),
along with 14 known ent/​kaurane diterpenoids. The structures of 1/​6 were
elucidated by spectroscopic data interpretation. Compound 1 is the first dimeric
ent/​kaurane derivative to have been reported from a plant in the family
Annonaceae. Certain useful NMR data were generalized to determine the
stereochemistry of C/​16 among the ent/​kaurane diterpenoids investigated.
ent/​Kaur/​16/​en/​19/​oic acid (9) and 16alpha/​hydro/​19/​al/​ent/​kauran/​17/​oic acid
(17) showed complete inhibitory effects on rabbit platelet aggregation at 200
microM.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 12398544 [PubMed /​ indexed for MEDLINE]

27: J Asian Nat Prod Res. 2002 Sep;4(3):171/​4.

Callus cultures of Annona squamosa for the production of annonaceous
acetogenins.

Wang LD, Qiu DY, Chen JY, Han YF, Zheng JH, Guo DA.

School of Pharmaceutical Sciences, Peking University, Beijing, China.

Callus cultures of Annona squamosa were induced using different explants
including petals, seed contents (megagametophyte and embryo) and fruits
(mesocarp). Growth of the calli induced from the explants was found to be
influenced by the type, concentration and ratio of auxin vs. cytokinin. The
content of squamocin (67.8 microg g(/​1) dry weight) in calli cultured on Gamborg
B/​5 medium containing 5.0 mg l(/​1) naphthalene acetic acid and 4.0 mg l(/​1)
zeatin was nearly seven times higher than that in intact fruits.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 12118503 [PubMed /​ indexed for MEDLINE]

28: Pest Manag Sci. 2002 Jan;58(1):33/​7.

Antimicrobial and pesticidal activity of partially purified flavonoids of Annona
squamosa.

Kotkar HM, Mendki PS, Sadan SV, Jha SR, Upasani SM, Maheshwari VL.

School of Life Sciences, North Maharashtra University, PB No 80, Jalgaon, India.

Foliar extracts of Annona squamosa (Family: Annonaceae) were screened for
antimicrobial and insecticidal activity against the common microbial infestants
of pulses and the stored grain pest pulse beetle, Callosobruchus chinensis
(Coleoptera: Bruchidae). Flavonoids isolated from aqueous extracts of A squamosa
showed antimicrobial activity against all the common microbial contaminants of
pulses and 80% insecticidal activity against C chinensis at a concentration of
0.07 mg ml/​1. Various physico/​chemical tests, chromatographic and spectroscopic
studies with partially purified aqueous extract indicated the presence of
flavonol type flavonoids. This may provide a useful beginning for the
development of botanical pesticides for post/​harvest safeguard of pulses.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 11838282 [PubMed /​ indexed for MEDLINE]

29: Southeast Asian J Trop Med Public Health. 2000;31 Suppl 1:174/​7.

Anti/​headlice activity of a preparation of Annona squamosa seed extract.

Tiangda CH, Gritsanapan W, Sookvanichsilp N, Limchalearn A.

Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok,
Thailand.

Various parts of Annona squamosa Linn. (custard apple) have long been used in
Thai folk medicine. The effectiveness of organic solvent extracts of custard
apple seeds and leaves against headlice has been reported. The present study is
focused on the efficacy and stability of seed extract prepared as a cream. A
petroleum ether extract of seeds was prepared as a 20% w/w oil in water cream
and tested for anti/​headlice activity in school girls. After a 3 hour/​hair
exposure to 20 g of freshly prepared custard apple cream, 95.34+//​1.96% of
headlice were killed. This killing rate was higher than that obtaned from the
control (cream base) or the standard drug (25% benzyl benzoate emulsion). The
anti/​headlice efficacy of the 6 and 12 month/​storage preparations kept in a
refrigerator and 12 month/​storage at room temperature were 99.19+//​0.60%,
97.55+//​2.06% and 89.47+//​3.64%, respectively, which were not significantly
different from that of the freshly prepared cream. This cream did not cause any
irritant effect on the scalp or neck skin while benzyl benzoate emulsion
produced burning sensation or redness. The results demonstrate that the
petroleum ether extract of Annona squamosa seeds prepared as a cream is stable
for at least 12 months. The custard apple cream may be, therefore, suitable for
use as an alternative therapy against headlice.

PMID: 11414452 [PubMed /​ indexed for MEDLINE]

30: Phytomedicine. 2001 Mar;8(2):115/​20.

Molluscicidal properties of some species of Annona.

dos Santos AF, Sant'Ana AE.

Laboratorio de Pesquisas em Recursos Naturais, Departamento de Quimica,
Universidade Federal de Alagoas, Maceio/​AL, Brazil.

In search for plant molluscicides for the vector control of schistosomiasis,
ethanolic extracts from different parts of six species of the Annonaceae family
were evaluated against adult forms and egg masses of Biomphalaria glabrata.
Results from accurate experiments indicate that the majority of analyzed
extracts possess properties lethal to Biomphalaria glabrata, some of them with
significant LD90 values (< 20 ppm), as showed for Annona crassiflora M: [pulp
and seed (LD50 = 13.21), steem (2.34), root bark (3.79)], Annona glabra L. [seed
(17.02)], Annona muricata [leaf (8.75)]. Emphasis is held mainly into Annona
muricata L. (leaf) and Annona squamosa Veil. (root) for presenting additional
toxicity toward snail egg masses.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 11315753 [PubMed /​ indexed for MEDLINE]

31: J Nat Prod. 2000 Dec;63(12):1707/​8.

Erratum in:
J Nat Prod 2002 Nov;65(11):1748.

Samoquasine A, a benzoquinazoline alkaloid from the seeds of Annona squamosa.

Morita H, Sato Y, Chan KL, Choo CY, Itokawa H, Takeya K, Kobayashi J.

Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo
060/​0812, Japan.

A benzooxyquinazoline alkaloid, samoquasine A (1), has been isolated from the
seeds of Annona squamosa, and its structure was elucidated by spectroscopic and
chemical methods.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 11141125 [PubMed /​ indexed for MEDLINE]

32: Lancet. 1999 Jul 24;354(9175):281/​6.

Comment in:
Lancet. 1999 Oct 23;354(9188):1472/​3.
Lancet. 1999 Oct 23;354(9188):1473/​4.
Lancet. 1999 Oct 23;354(9188):1474.

Possible relation of atypical parkinsonism in the French West Indies with
consumption of tropical plants: a case/​control study. Caribbean Parkinsonism
Study Group.

Caparros/​Lefebvre D, Elbaz A.

Department of Neurology, Centre Hospitalier Universitaire, des Antilles et de la
Guyane, Pointe a Pitre, Guadeloupe, French West Indies. lefebvdo@ais.gp

BACKGROUND: In Europe and North America, Parkinson's disease is the major form
of parkinsonism; less than 4% of cases are progressive supranuclear palsy (PSP)
and about 20% are atypical parkinsonism. The distribution of these subgroups is
different in the French West Indies. We aimed to define the clinical and
demographic specificity of these disorders in Guadeloupe and to investigate a
postulated link with consumption of herbal tea and fruits from the Annonaceae
family (Annona muricata and Annona squamosa), which contain neurotoxic
benzyltetrahydroisoquinoline alkaloids. METHODS: Between September, 1996, and
August, 1998, 87 consecutive patients with parkinsonism were referred to the
single neurological department in Guadeloupe. After detailed clinical,
neurophysiological, cognitive, and neuroradiological assessment, they were
classified by generally accepted criteria as having Parkinson's disease, PSP, or
atypical parkinsonism. We compared the amount of tropical fruits and herbal tea
consumed by the various parkinsonian subgroups and by frequency/​matched controls
(patients with benign symptoms and no neurodegenerative disease). FINDINGS: Of
the 87 patients, 22 had Parkinson's disease, 31 had PSP, 30 had atypical
parkinsonism, and four had atypical parkinsonism associated with motor neuron
disease, 44 of the patients with PSP or atypical parkinsonism were male. The
patients with atypical parkinsonism had symmetrical rigidity and bradykinesia,
and no levodopa peak/​dose dyskinesias. Patients with PSP differed from those
with atypical parkinsonism because they had supranuclear vertical down/​gaze
palsy, severe gait and balance problems, and frontal/​lobe syndrome. 29 patients
with PSP reported regular consumption of pawpaw fruit, and 26 drank herbal tea.
30 patients with atypical parkinsonism reported regular consumption of pawpaw
fruit, and 24 drank herbal tea. Both of these groups consumed significantly more
fruit and herbal tea than patients with Parkinson's disease (fruit: odds ratio
23.6; herbal tea: 28.2); and controls (fruit: 20.7; herbal tea: 6.48).
INTERPRETATION: Our study confirms the over/​representation of atypical
parkinsonism and PSP in patients with parkinsonism in the French West Indies.
Chronic exposure to neurotoxic alkaloids could be an important aetiological
factor because these compounds induce parkinsonism in animals. A larger
epidemiological study, to clarify the link between these fruits with atypical
parkinsonism and PSP, is proposed.

PMID: 10440304 [PubMed /​ indexed for MEDLINE]

33: J Ethnopharmacol. 1999 Mar;64(3):227/​33.

Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on
Maytenus senegalensis (Lam.) Exell.

El Tahir A, Satti GM, Khalid SA.

Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan.

The antiplasmodial activity of plant extracts related to four families was
tested on chloroquine sensitive strain 3D7 and chloroquine resistant strain Dd2
of Plasmodium falciparum. The methanolic extract of Harrisonia abyssinica
(Simaroubaceae) inhibited Dd2 with IC50 value of 4.7 microg/ml, while in 3D7,
the IC50 value was 10 microg/ml. Most of the plants from the family Meliaceae
showed highly potent antiplasmodial activity against the two tested strains.
Khaya senegalensis, Azadirachta indica and Trichilia emetica showed IC50 values
less than 5 microg/ml. The methanolic extract of Annona squamosa (Annonaceae)
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 Dd2. Maytenus senegalensis
(Celastraceae) possessed IC50 values of 3.9 on 3D7, 10 microg/ml on Dd2 and had
no effect on lymphocyte proliferation even at the highest tested concentration;
the IC50 was greater than 100 microg/ml. Liquid/​liquid separation of the
methanolic extract of M. senegalensis revealed that the dichloromethane extract
possessed an IC50 value of only 2.1 microg/ml. Column fractionation of
dichloromethane extract gave four fractions and fraction two showed an IC50
value of 0.5 microg/ml. Preliminary phytochemical analysis of dichloromethane
fraction revealed terpenoids and traces of phenolic principles but no alkaloid,
tannins or flavonoids were detected.

Publication Types:
In Vitro

PMID: 10363837 [PubMed /​ indexed for MEDLINE]

34: Bioorg Med Chem. 1998 May;6(5):569/​75.

Three new bioactive bis/​adjacent THF/​ring acetogenins from the bark of Annona
squamosa.

Hopp DC, Alali FQ, Gu ZM, McLaughlin JL.

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University,
West Lafayette, IN 47907/​1333, USA.

Continuing work on the bioactivity/​directed fractionation of the bark of Annona
squamosa has resulted in the discovery of three new Annonaceous acetogenins,
(2,4/​cis and trans)/​squamolinone (1), (2,4/​cis and trans)/​9/​oxoasimicinone (2),
and bullacin B (3). Compounds 1/​3 are all adjacent bis/​THF ring acetogenins with
2 representing the first bis/​ring acetogenin to contain a carbonyl along its
aliphatic chain. Compound 3 was selectively cytotoxic in a panel of six human
tumor cell lines with a potency of nearly a million times that of adriamycin
against the MCF/​7 (human breast adenocarcinoma) cell line.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 9629470 [PubMed /​ indexed for MEDLINE]

35: Phytochemistry. 1998 Mar;47(5):803/​9.

Mono/​THF ring annonaceous acetogenins from Annona squamosa.

Hopp DC, Alali FQ, Gu ZM, McLaughlin JL.

Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy
and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907, USA.

Continuing work on the bark of Annona squamosa Rich. (Annonaceae), directed by
the brine shrimp lethality test (BST), has resulted in the isolation of three
new Annonaceous acetogenins, 4/​deoxyannoreticuin, cis/​4/​deoxyannoreticuin, and
(2,4/​cis and trans)/​squamoxinone. The first two are additional examples of
acetogenins isolated from this plant species which contain the unusual feature
of an oxygen functionality at the C/​9 position. They have a hydroxylated
mono/​THF ring with respective threo/trans/threo and threo/cis/threo relative
stereochemistries. The latter compound is a ketolactone mixture which has the
same relative stereochemistry around the THF ring and the same spatial
relationship between the THF ring and the hydroxyl group along the aliphatic
chain as 4/​deoxyannoreticuin, but is two methylene units longer. Additionally,
the isolated hydroxyl group is at C/​11, while the THF ring starts at C/​17,
instead of at C/​9 and C/​15, respectively, as for the first two compounds. All
three compounds showed moderate, but significant, cytotoxicities against a panel
of six human tumor cell lines with (2,4 cis and trans)/​squamoxinone showing
promising selectivity against the pancreatic cell line (PACA/​2).

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 9542173 [PubMed /​ indexed for MEDLINE]

36: J Nat Prod. 1997 Jun;60(6):581/​6.

Novel mono/​tetrahydrofuran ring acetogenins, from the bark of Annona squamosa,
showing cytotoxic selectivities for the human pancreatic carcinoma cell line,
PACA/​2.

Hopp DC, Zeng L, Gu ZM, Kozlowski JF, McLaughlin JL.

Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy
and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907/​1333,
USA.

The bark of Annona squamosa yielded three new mono/​tetrahydrofuran (THF) ring
acetogenins, each bearing two flanking hydroxyls and a carbonyl group at the C/​9
position. These compounds were isolated using the brine shrimp lethality assay
as a guide for the bioactivity/​directed fractionation. (2,4/​cis and
trans)/​Mosinone A (1) is a mixture of ketolactone compounds bearing a
threo/trans/threo ring relationship and s double bond two methylene units away
from the flanking hydroxyl. The other two new acetogenins differ in their
stereochemistries around the THF ring; mosin B (2) has a threo/trans/erythro
configuration across the ring, and mosin C (3) possesses a threo/cis/threo
relative stereochemistry. Also found was annoreticuin/​9/​one (4), a known
acetogenin that bears a threo/trans/threo ring configuration and a C/​9 carbonyl
and is new to this species. The structures were elucidated based on
spectroscopic and chemical methods. Compounds 1/​4 all showed selective cytotoxic
activity against the human pancreatic tumor cell line, PACA/​2, with potency
10/​100 times that of Adriamycin.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 9214729 [PubMed /​ indexed for MEDLINE]

37: Mycopathologia. 1997/​1998;140(3):141/​7.

Examination of some morphologically unusual cultures of Phytophthora species
using a mitochondrial DNA miniprep technique and a standardised sporangium
caducity assessment.

Hall GS.

International Mycological Institute, Bakeham Lane, Egham, TW20 9TY, UK.

Using the mitochondrial DNA miniprep technique, the identity of sixteen
morphologically unusual cultures allocated to Phytophthora nicotianae,
Phytophthora mexicana or Phytophthora porri was determined by comparison with a
library of mtDNA band patterns obtained from reference cultures. Seven cultures
were identified as Phytophthora nicotianae (including those assigned to
Phytophthora mexicana and Phytophthora porri), six as strains of Phytophthora
palmivora with small, ovoid, weakly caducous sporangia, and one as Phytophthora
citrophthora. Some cultures of P. nicotianae had a low percentage of caducous
sporangia. Percentage sporangium caducity, but not sporangium L:B ratio, is
considered a useful taxonomic criterion for separating species morphologically
similar to Phytophthora nicotianae. One culture from tobacco in New Zealand had
a highly unusual morphology and a unique DNA band pattern, but was not
identifiable. One culture from Acacia mearnsii in South Africa had a unique DNA
band pattern which was identical to that of an isolate from Annona squamosa from
Australia previously identified as Phytophthora palmivora, the precise identity
of which is still unclear. The identity of most isolates from diseased durian
was found to be Phytophthora palmivora, confirming its role as the main
pathogen, but P. nicotianae was also identified from this host.

PMID: 16284813 [PubMed]

38: J Nat Prod. 1996 Jun;59(6):635/​7.

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.

Wu YC, Hung YC, Chang FR, Cosentino M, Wang HK, Lee KH.

Graduate Institute of Natural Products, Kaohsiung Medical College, Taiwan,
Republic of China.

Phytochemical analysis of the fruits of Annona squamosa yielded 12 known kaurane
derivatives (1/​11, 13) and two new kaurane diterpenoids, which have been named
annosquamosin A (16 beta/​hydroxy/​17/​acetoxy/​ent/​kauran/​19/​al) (12) and
annosquamosin B (19/​nor/​ent/​kaurane/​4 alpha,16 beta,/​17/​triol) (14). The
structures of the new compounds were established by spectral analyses and
chemical evidence. Among these 14 compounds, 16 beta,
17/​dihydroxy/​ent/​kauran/​19/​oic acid (2) showed significant activity against HIV
replication in H9 lymphocyte cells with an EC50 value of 0.8 microgram/mL
(therapeutic index > 5).

Publication Types:
Research Support, Non/​U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 8786370 [PubMed /​ indexed for MEDLINE]

39: J Nat Prod. 1996 Feb;59(2):97/​9.

Squamotacin: an annonaceous acetogenin with cytotoxic selectivity for the human
prostate tumor cell line (PC/​3).

Hopp DC, Zeng L, Gu Z, McLaughlin JL.

Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West
Lafayette, Indiana 47907/​1333, USA.

The bark extracts of Annona squamosa yielded a new bioactive acetogenin,
squamotacin (1), and the known compound, molvizarin (2), which is new to this
species. Compound 1 is identical to the potent acetogenin, bullatacin (3),
except that the adjacent bistetrahydrofuran (THF) rings and their flanking
hydroxyls are shifted two carbons toward the gamma/​lactone ring. Compound 1
showed cytotoxic selectively for the human prostate tumor cell line (PC/​3), with
a potency of over 100 million times that of Adriamycin.

Publication Types:
Research Support, U.S. Gov't, P.H.S.

PMID: 8991957 [PubMed /​ indexed for MEDLINE]

40: J Am Mosq Control Assoc. 1993 Mar;9(1):84/​7.

Larvicidal and chemosterilant activity of Annona squamosa alkaloids against
Anopheles stephensi.

Saxena RC, Harshan V, Saxena A, Sukumaran P, Sharma MC, Kumar ML.

Post Graduate Department of Zoology, S. S. L. Jain College, Vidisha, India.

Alkaloids isolated from Annona squamosa have shown larvicidal growth/​regulating
and chemosterilant activities against Anopheles stephensi at concentrations of
50 to 200 ppm. Adults exposed as larvae to different treatments showed reduced
fecundity and fertility in females. Mortality in the larvae, pupae and adults
produced about a 52/​92% decrease in the laboratory experiment. The total
developmental period was slightly reduced from the control. Treatment with the
alkaloids had a significant effect on the mortality, emergence and reproductive
physiology of An. stephensi.

PMID: 8468579 [PubMed /​ indexed for MEDLINE]

41: Yao Xue Xue Bao. 1993;28(6):428/​31.

[Studies on total synthesis of squamosamide]

[Article in Chinese]

Ji XS, Liang XT.

Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.

A new natural compound squamosamide isolated from Annona squamosa, was
synthesized. This compound was characterized by 1H, 13CNMR and MS.

Publication Types:
English Abstract

PMID: 8249600 [PubMed /​ indexed for MEDLINE]

42: Yao Xue Xue Bao. 1992;27(3):185/​90.

[Studies on the chemical constituents of Annona squamosa]

[Article in Chinese]

Yang XJ, Xu LZ, Sun NJ, Wang SC, Zheng.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences,
Beijing.

Twelve compounds were isolated from Annona squamosa. Their structures were
identified as liriodenine (AS/​1), moupinamide (AS/​2), /​(/​)/​kauran/​16
alpha/​ol/​19/​oic acid (AS/​3), 16 beta, 17/​dihydroxy/​(/​)/​kauran/​19/​oic acid
(AS/​4), anonaine (AS/​5), 16 alpha, 17/​dihydroxy/​(/​)/​kauran/​19/​oic acid (AS/​6),
(/​)/​isokaur/​15(16)/​en/​17,19/​dioic acid (AS/​7), squamosamide (AS/​8), 16
alpha/​methoxy/​(/​)/​kauran/​19/​oic acid (AS/​9), sachanoic acid (AS/​10),
(/​)/​kauran/​19/​al/​17/​oic acid (AS/​11), daucosterol (AS/​12). Among them, AS/​8 is a
new amide, AS/​9 is a new natural product.

Publication Types:
English Abstract

PMID: 1414383 [PubMed /​ indexed for MEDLINE]

43: Planta Med. 1990 Jun;56(3):317/​319.

Annonacins and Annonastatin from Annona squamosa.

Lieb F, Nonfon M, Wachendorff/​Neumann U, Wendisch D.

Zentralbereich Zentrale Forschung der Bayer AG, D/​5090 Leverkusen,
Bundesrepublik Deutschland.

Annonacin ( 1), annonacin A ( 6), and annonastatin ( 7) were isolated from the
seeds of ANNONA SQUAMOSA L. (Annonaceae). Compounds 6 and 7 are described for
the first time. The relative configuration of the tetrahydrofuran core of 1
(with hitherto unknown configuration), as well as those of compounds 6, and 7
were established by (13)C/​ and (1)H/​NMR spectroscopy using data of the
derivatives 8/​ 11.

PMID: 17221428 [PubMed /​ as supplied by publisher]

44: Planta Med. 1990 Jun;56(3):312/​316.

The Relative Configuration of Acetogenins Isolated from Annona squamosa: Annonin
I (Squamocin) and Annonin VI.

Born L, Lieb F, Lorentzen JP, Moeschler H, Nonfon M, Sollner R, Wendisch D.

Zentralbereich Zentrale Forschung der Bayer AG, D/​5090 Leverkusen,
Bundesrepublik Deutschland.

Annonin I ( 1) and anonin VI ( 9) were isolated from the seeds of ANNONA
SQUAMOSA L. (Annonaceae). The constitution of 1 is identical with that of
squamocin, isolated by Fujimoto et al. (8). The relative configuration of 1 was
elucidated by X/​ray diffraction analysis of a derivative. The constitution and
relative configuration of 9 was established by (13)C/​ and (1)H/​NMR spectroscopy
using data of derivatives.

PMID: 17221427 [PubMed /​ as supplied by publisher]

45: J Nat Prod. 1990 Jan/​Feb;53(1):81/​6.

Bullatacin, bullatacinone, and squamone, a new bioactive acetogenin, from the
bark of Annona squamosa.

Li XH, Hui YH, Rupprecht JK, Liu YM, Wood KV, Smith DL, Chang CJ, McLaughlin JL.

Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and
Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.

Activity/​directed fractionation of the stem bark of Annona squamosa, monitoring
with brine shrimp lethality, led to the isolation of the highly bioactive
acetogenins bullatacin [1] and bullatacinone [2], thus demonstrating a new
abundant plant source for these potent compounds. A new keto/​monotetrahydrofuran
acetogenin with a ketolactone terminus, as first seen in bullatacinone [2], was
also isolated, characterized by spectral analyses, and named squamone [3]. The
cytotoxicities of 3 were increased significantly by reduction of the two keto
groups to hydroxyls, and the tetrahydrosquamone [7] and bullatacinone [2] both
showed selective cytotoxicities to MCF/​7 human breast carcinoma. Liriodenine and
(/​)/​kaur/​16/​en/​19/​oic acid were also isolated.

Publication Types:
Research Support, Non/​U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

PMID: 2348205 [PubMed /​ indexed for MEDLINE]

46: Chem Pharm Bull (Tokyo). 1988 Dec;36(12):4802/​6.

Squamocin, a new cytotoxic bis/​tetrahydrofuran containing acetogenin from Annona
squamosa.

Fujimoto Y, Eguchi T, Kakinuma K, Ikekawa N, Sahai M, Gupta YK.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 3246042 [PubMed /​ indexed for MEDLINE]

47: Planta Med. 1979 Mar;35(3):283/​5.

Post/​coital antifertility activity of Annona squamosa and Ipomoea fistulosa.

Mishra A, Dogra JV, Singh JN, Jha OP.

PMID: 432307 [PubMed /​ indexed for MEDLINE]

48: Planta Med. 1975 Aug;28(1):97/​100.

Phytochemical, pharmacological, antibacterial and anti/​ovulatory studies on
Annona squamosa.

Vohora SB, Kumar I, Naqvi SA.

PMID: 1178793 [PubMed /​ indexed for MEDLINE]

49: Nature. 1960 Jul 23;187:343/​4.

Unproductivity in the colchicine/​induced tetraploids of Annona squamosa L.

ISLAM AS.

PMID: 14405938 [PubMed /​ indexed for MEDLINE]