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http://www.rain-tree.com/graviola.htm

 

GRAVIOLA

(Annona muricata

 

Family: Annonaceae

 

Genus: Annona

 

Species: muricata

 

Synonyms: Annona macrocarpa, A. bonplandiana, A. cearensis, Guanabanus muricatus

 

Common names: Graviola, soursop, guanábana, guanábano, guanavana, guanaba,

corossol épineux, huanaba, toge-banreisi, durian benggala, nangka blanda,

cachiman épineux

 

Part Used: Leaves, fruit, seeds, bark, roots

 

 

 

PLANT DESCRIPTION Documented Properties

& Actions:Antibacterial, anthelmintic, anticancerous, anticonvulsant,

antidepressant, antifungal, antimicrobial, antineoplastic, antiparasitic,

antispasmodic, antitumorous, antiviral, astringent, cardiodepressant,

cytostatic, cytotoxic, febrifuge, hypotensive, insecticide, nervine, pectoral,

piscicide, sedative, stomachic, vasodilator, vermifuge Plant

Chemicals

Include:Annonaceous acetogenins: annocatalin, annohexocin, annomonicin,

annomontacin, annomuricatin A & B, annomuricin A thru E, annomutacin, annonacin,

(multiple iso, cis, one, etc.), annonacinone, annopentocin A thru C,

cis-annonacin, cis-corossolone, cohibin A thru D, corepoxylone, coronin,

corossolin, corossolone, donhexocin, epomuricenin A & B, gigantetrocin,

gigantetrocin A & B, gigantetrocinone, gigantetronenin, goniothalamicin,

iso-annonacin, javoricin, montanacin, montecristin, muracin A thru G,

muricapentocin, muricatalicin, muricatalin, muri-catenol, muricatetrocin A & B

muricatin D, muricatocin A thru C, muricin H, muricin I, muricoreacin,

murihexocin 3, murihexocin A thru C, murihexol, murisolin, robustocin,

rolliniastatin 1 & 2, saba-delin, solamin, uvariamicin I & IV, xylomaticin

 

Graviola is a small, upright evergreen tree, 5-6 m high, with large, glossy,

dark green leaves. It produces a large, heart-shaped, edible fruit that is 15-23

cm in diameter, is yellow-green in color, and has white flesh inside. Graviola

is indigenous to most of the warmest tropical areas in South and North America,

including the Amazon. The fruit is sold in local markets in the tropics, where

it is called guanábana in Spanish-speaking countries and graviola in Brazil. The

fruit pulp is excellent for making drinks and sherbets and, though slightly

sour-acid, can be eaten out of hand.

 

All parts of the graviola tree are used in natural medicine in the tropics,

including the bark, leaves, roots, fruit, and fruit seeds. Different properties

and uses are attributed to the different parts of the tree. Generally, the fruit

and fruit juice are taken for worms and parasites, to cool fevers, as a

lactagogue (to increase mother's milk after childbirth), and as an astringent

for diarrhea and dysentery. The crushed seeds are used as a vermifuge and

anthelmintic against internal and external parasites, head lice, and worms. The

bark, leaves, and roots are considered sedative, antispasmodic, hypotensive, and

nervine, and a tea is made for various disorders toward those effects.

 

Graviola has a long, rich history of use in herbal medicine as well as lengthy

recorded indigenous use. In the Peruvian Andes, a leaf tea is used for catarrh

(inflammation of mucous membranes) and the crushed seed is used to kill

parasites. In the Peruvian Amazon the bark, roots, and leaves are used for

diabetes and as a sedative and antispasmodic. Indigenous tribes in Guyana use a

leaf and/or bark tea as a sedative and heart tonic. In the Brazilian Amazon a

leaf tea is used for liver problems, and the oil of the leaves and unripe fruit

is mixed with olive oil and used externally for neuralgia, rheumatism, and

arthritis pain. In Jamaica, Haiti, and the West Indies, the fruit and/or fruit

juice is used for fevers, parasites and diarrhea, and as a lactagogue; the bark

or leaf is used as an antispasmodic, sedative, and nervine for heart conditions,

coughs, grippe, difficult childbirth, asthma, asthenia, hypertension, and

parasites.

 

Many bioactive compounds and phytochemicals have been found in graviola, as

scientists have been studying its properties since the 1940s. Its many uses in

natural medicine have been validated by scientific research. Several studies by

different researchers demonstrated that the bark as well as the leaves had

hypotensive, antispasmodic, anticonvulsant, vasodilator, smooth-muscle relaxant,

and cardiodepressant activities in animals. Researchers verified graviola leaf's

hypotensive properties in rats again in 1991. Several studies over the years

have demonstrated that leaf, bark, root, stem, and seed extracts of graviola are

antibacterial in vitro against numerous pathogens, and that the bark has

antifungal properties. Graviola seeds demonstrated active antiparasitic

properties in a 1991 study, and a leaf extract showed to be active against

malaria in two other studies (in 1990 and 1993). The leaves, root, and seeds of

graviola demonstrated insecticidal properties, with the seeds demonstrating

strong insecticidal activity in an early 1940 study. In a 1997 clinical study,

novel alkaloids found in graviola fruit exhibited antidepressive effects in

animals.

 

In an 1976 plant screening program by the National Cancer Institute, graviola

leaves and stem showed active cytotoxicity against cancer cells and researchers

have been following up on these findings since. Much of the cancer research on

graviola focuses on a novel set of phyto-chemicals called Annonaceous

acetogenins. Graviola produces these natural compounds in its leaf and stem,

bark, and fruit seeds. Three separate research groups have isolated these

acetogenin compounds in graviola which have demonstrated significant

antitumorous and anticancerous properties, and selective toxicity against

various types of cancer cells (without harming healthy cells) publishing eight

clinical studies on their findings. Many of the acetogenins have demonstrated

selective toxicity to tumor cells at very low dosages--as little as 1 part per

million. Four studies were published in 1998 which further specify

phytochemicals and acetogenins which are demonstrating the strongest

anticancerous, antitumorous, and antiviral properties. Thus far, specific

acetogenins in graviola have been reported to be selectively toxic to these

types of tumor cells: lung carcinoma cell lines; human breast solid tumor lines;

prostate adenocarcinoma; pancreatic carcinoma cell lines; colon adenocarcinoma

cell lines; liver cancer cell lines; human lymphoma cell lines; and multi-drug

resistant human breast adenocarcinoma.

 

Annonaceous acetogenins are only found in the Annonaceae family (to which

graviola belongs). In general, various Annonaceous acetogenins in the plant

family have been documented with antitumorous, antiparasitic, pesticidal,

antiprotozoal, antifeedant, anthelmintic, and antimicrobial activities. Mode of

action studies in three separate laboratories have recently determined that

these acetogenins are superb inhibitors of enzyme processes that are only found

in the membranes of cancerous tumor cells. Purdue University, in West Lafayette,

Indiana, has conducted a great deal of the research on the acetogenins, much of

which has been funded by The National Cancer Institute and/or the National

Institute of Health (NIH). Thus far, Purdue University and/or its staff have

filed at least nine U.S. and/or international patents on their work around the

antitumorous and insecticidal properties and uses of these acetogenins. In one

of their reviews, titled " Recent Advances in Annonaceous Acetogenins, " they

state, " Recently, we reported that the Annonaceous acetogenins can selectively

inhibit the growth of cancerous cells and also inhibit the growth of adriamycin

resistant tumor cells. As more acetogenins have been isolated and additional

cytotoxicity assays have been conducted, we have noticed that, although most of

acetogenins have high potencies among several solid human tumor cell lines, some

of the derivatives within the different structural types and some positional

isomers showed remarkable selectivities among certain cell lines; e.g., against

prostate cancer (PC-3). We now understand the primary modes of action for the

acetogenins. They are potent inhibitors of NADH: ubiquinone oxidoreductase,

which is in an essential enzyme in complex I leading to oxidative

phosphorylation in mitochondria. A recent report showed that they act directly

at the ubiquinone-catalytic site(s) within complex I and in microbial glucose

dehydrogenase. They also inhibit the ubiquinone-linked NADH oxidase that is

peculiar to the plasma membranes of cancerous cells. "

 

In 1997, Purdue University published information with promising news that

several of the Annonaceous acetogenins " . . . not only are effective in killing

tumors that have proven resistant to anticancer agents, but also seem to have a

special affinity for such resistant cells. " In several interviews after this

information was publicized, the head pharmacologist in Purdue's research

explained how this worked. As he explains it, cancer cells that survive

chemotherapy can develop resistance to the agent originally used as well as to

other, even unrelated, drugs. This phenomenon is called multi-drug resistance

(MDR). One of the ways that cancer cells develop resistance to chemotherapy

drugs is by creating an intercellular efflux pump called a P-glycoprotein

mediated pump. These types of pumps are capable of pushing anticancer agents out

of the cell before they can kill it. On average, only about two percent of the

cancer cells in any given person might develop this pump--but they are the two

percent that can eventually grow and expand to create multi-drug-resistant

tumors. Some of the latest research on acetogenins reported that they were

capable of shutting down these intercellular pumps, thereby killing MDR tumors.

Purdue researchers reported that the acetogenins preferentially killed

multi-drug-resistant cancer cells by blocking the transfer of ATP--the chief

source of cellular energy--into them. A tumor cell needs energy to grow and

reproduce, and a great deal more to run its pump and expel attacking agents. By

inhibiting energy to the cell, it can no longer run its pump. When acetogenins

block ATP to the tumor cell over time, the cell no longer has enough energy to

operate sustaining processes--and it dies. Normal cells seldom develop such a

pump; therefore, they don't require large amounts of energy to run a pump and,

generally, are not adversely affected by ATP inhibitors. Purdue researchers

reported that 14 different acetogenins tested thus far demonstrate potent ATP

blocking properties (including several found only in graviola). They also

reported that 13 of these 14 acetogenins tested were more potent against MDR

breast cancer cells than all three of the standard drugs (adriamycin,

vincristine, and vinblastine) they used as controls.

 

An interesting in vivo study was published in March of 2002 by researchers in

Japan, who were studying various acetogenins found in several species of plants.

They inoculated mice with Lewis lung carcinoma cancer cells. One third received

nothing, one third received the chemotherapy drug adriamycin, and one third

received the main graviola acetogenin, annonacin (at a dosage of 10 mg/kg). At

the end of two weeks, five of the six in the untreated control group were still

alive and lung tumor sizes were then measured. The adriamycin group showed a

54.6% reduction of tumor mass over the control group--but 50% of the animals had

died from toxicity (three of six). The mice receiving annonacin were all still

alive, and the tumors were inhibited by 57.9%--slightly better than

adriamycin--and without toxicity. This led the researchers to summarize; " This

suggested that annonacin was less toxic in mice. On considering the antitumor

activity and toxicity, annonacin might be used as a lead to develop a potential

anticancer agent. " Its important to note, however, that annonacin only inhibited

the normal growth of the lung tumors during this two-week period; it did not

eradicate the tumors nor stop their growth altogether.

 

Cancer research is ongoing on these important plants and plant chemicals, as

several pharmaceutical companies and universities continue to research, test,

patent, and attempt to synthesize these chemicals into new chemotherapeutic

drugs. In addition, researchers have reported that NADH dehydrogenase inhibitors

can suppress HIV infection. As this is a familiar property of Annonaceous

acetogenins, several acetogenins found in graviola and other Annona plants have

been submitted to the NIH anti-AIDS screening program by Purdue University;

research work is continuing in this area as well.

 

One researcher summarized his work eloquently: " At the time of preparation

(August 1998) of this current review, over 350 Annonaceous acetogenins have been

isolated from 37 species. Our preliminary efforts show that about 50%, of over

80 Annonaceous species screened, are significantly bioactive and are worthy of

fractionation; thus, this class of compounds can be expected to continue to grow

at an exponential rate in the future, provided that financial support for such

research efforts can be found. With the demise of the world's tropical rain

forests, such work is compelling before the great chemical diversity, contained

within these endangered species, is lost. " Perhaps--if enough people believe

that the possible cure for cancer or AIDS truly is locked away in a rainforest

plant--we will take the steps needed to protect our remaining rainforests from

destruction.

 

 

Traditional Remedy: The therapeutic dosage is reported to be 5-7 grams daily in

capsules or tablets (in 3-4 divided dosages). A standard infusion (one cup 2-3

times daily) or a 4:1 standard tincture (2-4 ml three times daily) can be

substituted if desired. See Traditional Herbal Remedies Preparation Methods page

if necessary for definitions.

 

Contraindications:

Graviola has demonstrated uterine stimulant activity in an animal study

(rats) and should therefore not be used during pregnancy.

 

Graviola has demonstrated hypotensive, vasodilator, and cardiodepressant

activities in animal studies and is contraindicated for people with low blood

pressure. People taking antihypertensive drugs should check with their doctors

before taking graviola and monitor their blood pressure accordingly (as

medications may need adjusting).

 

Graviola has demonstrated significant in vitro antimicrobial properties.

Chronic, long-term use of this plant may lead to die-off of friendly bacteria in

the digestive tract due to its antimicrobial properties. Supplementing the diet

with probiotics and digestive enzymes is advisable if this plant is used for

longer than 30 days.

 

Graviola has demonstrated emetic properties in one animal study with pigs.

Large single dosages may cause nausea or vomiting. Reduce the usage accordingly

if this occurs.

 

One study with rats given a stem-bark extract intragastrically (at 100 mg/kg)

reported an increase in dopamine, norepinephrine, and monomine oxidase activity,

as well as a inhibition of serotonin release in stress-induced rats. As such,

the use of this plant is probably contraindicated in combination with MAO

inhibitors and some prescription antidepressants. Check with your doctor first

if you are taking prescription antidepressants or MAO inhibitor drugs prior to

taking graviola.

 

Alcohol extracts of graviola leaf showed no toxicity or side effects in mice

at 100 mg/kg; however, at a dosage of 300 mg/kg, a reduction in explorative

behavior and mild abdominal constrictions was observed. If sedation or

sleepiness occurs, reduce the amount used.

 

 

 

Drug Interactions: None have been reported; however, graviola may potentiate

antihypertensive and cardiac depressant drugs. It may potentiate antidepressant

drugs and interfere with MAO-inhibitor drugs. See contraindications above.

 

 

 

 

ETHNOBOTANY: WORLDWIDE USES BrazilAbscess, analgesic, anthelmintic,

antispasmodic, astringent, bronchitis, calmative, chest problems, cough,

diabetes, diarrhea, dysentery, edema, emetic, fever, intestinal colic, liver

problems, neuralgia, parasites, rheumatismCaribbeanAntispasmodic, chill, fever,

flu, indigestion, nervousness, palpitation, rash, sedative, skin

diseaseCuraçaoChildbirth, gallbladder, nervousness, parturition, sedative, tea,

tranquilizerHaitiAsthenia, cataplasm, cicatrizant, cough, diarrhea, emetic,

fever, grippe, heart conditions, lactagogue, nervine, parasites, pediculicide,

pellagra, sedative, soporific, sore, spasm, stomachicJamaicaAntispasmodic,

asthenia, asthma, diuretic, fevers, heart conditions, hypertension, lactagogue,

nervine, parasites, sedative, vermifuge

 

MalaysiaAstringent, boil, cough, diarrhea, dermatosis, hypertension, rheumatism,

stypticMexicoAstringent, diarrhea, dysentery, fever, liqueur, pectoral,

ringworm, scurvyPanamaAnthelmintic, diarrhea, dyspepsia, kidney, piscicide,

ulcer (stomach), vermifugePeruAntiparasitic, antispasmodic, catarrh, diabetes,

diarrhea, dysentery, fever, hypertension, indigestion, insecticide, lice, liver

disorders, sedative, tumors (skin), ulcers (internal)Trinidad Depurative,

fainting, flu, galactagogue, high blood pressure, hypertension, insomnia,

palpitation, ringwormsWest IndiesAsthma, childbirth, diarrhea, hypertension,

lactagogue, parasites, wormsElsewhereAnalgesic, antiphlogistic, arthritis,

asthma, astringent, bilious, childbirth, cyanogenetic, diarrhea, dysentery,

febrifuge, heart, insecticide, kidney, lactagogue, liver, malaria, pectoral,

pediculicide, piscicide, ringworm, scurvy, sedative, stomach, tranquilizer

 

 

 

 

 

 

 

 

References:

Feng, P. C., et al. " Pharmacological screening of some West Indian medicinal

plants. " J. Pharm. Pharmacol. 1962; 14: 556-61.

Meyer, T. M. " The alkaloids of Annona muricata. " Ing. Ned. Indie. 1941; 8(6):

64.

Carbajal, D., et al. " Pharmacological screening of plant decoctions commonly

used in Cuban folk medicine. " J. Ethnopharmacol. 1991; 33(1/2): 21-4.

Misas, C. A. J., et al. " Contribution to the biological evaluation of Cuban

plants. IV. " Rev. Cubana Med. Trop. 1979; 31(1): 29-35.

Sundarrao, K., et al. " Preliminary screening of antibacterial and antitumor

activities of Papua New Guinean native medicinal plants. " Int. J. Pharmacog.

1993; 31(1): 3-6.

Heinrich, M., et al. " Parasitological and microbiological evaluation of Mixe

Indian medicinal plants (Mexico). " J. Ethnopharmacol. 1992; 36(1): 81-5.

Lopez, Abraham A. M. " Plant extracts with cytostatic properties growing in

Cuba. I. " Rev. Cubana Med. Trop. 1979; 31(2): 97-104.

Bories, C., et al. " Antiparasitic activity of Annona muricata and Annona

cherimolia seeds. " Planta Med. 1991; 57(5): 434-36.

Antoun, M. D., et al. " Screening of the flora of Puerto Rico for potential

antimalarial bioactives. " Int. J. Pharmacog. 1993; 31(4): 255-58.

Gbeassor, M., et al. " In vitro antimalarial activity of six medicinal

plants. " Phytother. Res. 1990; 4(3): 115-17.

Tattersfield, F., et al. " The insecticidal properties of certain species of

Annona and an Indian strain of Mundulea sericea (Supli). " Ann. Appl. Biol. 1940;

27: 262-73.

Hasrat, J. A., et al. " Isoquinoline derivatives isolated from the fruit of

Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats: unexploited

antidepressive (lead) products. " J. Pharm. Pharmacol. 1997; 49(11): 1145-49.

Anon. Unpublished data, National Cancer Institute. Nat Cancer Inst Central

Files (1976). From NAPRALERT Files, University of Illinois, 1995.

Zeng, L., et al. " Five new monotetrahydrofuran ring acetogenins from the

leaves of Annona muricata. " J. Nat. Prod. 1996; 59(11): 1035-42.

Rieser, M. J., et al. " Five novel mono-tetrahydrofuran ring acetogenins from

the seeds of Annona muricata. " J. Nat. Prod. 1996; 59(2): 100-8.

Wu, F. E., et al. " Additional bioactive acetogenins, annomutacin and

(2,4-trans and cis)-10R-annonacin-A-ones, from the leaves of Annona muricata. "

J. Nat. Prod. 1995; 58(9): 1430-37.

Wu, F. E., et al. " New bioactive monotetrahydrofuran Annonaceous acetogenins,

annomuricin C and muricatocin C, from the leaves of Annona muricata. " J. Nat.

Prod. 1995; 58(6): 909-15.

Wu, F. E., et al. " Muricatocins A and B, two new bioactive

monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata. "

J. Nat. Prod. 1995; 58(6): 902-8.

Wu, F. E., et al. " Two new cytotoxic monotetrahydrofuran Annonaceous

acetogenins, annomuricins A and B, from the leaves of Annona muricata. " J. Nat.

Prod. 1995; 58(6): 830-36.

Rieser, M. J., et al. " Bioactive single-ring acetogenins from seed extracts

of Annona muricata. " Planta Med. 1993; 59(1): 91-2.

Rieser, M. J., et al. " Muricatacin: a simple biologically active acetogenin

derivative from the seeds of Annona muricata (Annonaceae) " Tetrahedron Lett.

1991; 32(9):1137-40.

Kim, G. S., et al. " Muricoreacin and murihexocin C, mono-tetrahydrofuran

acetogenins, from the leaves of Annona muricata. Phytochemistry 1998; 49(2):

565-71.

Padma, P., et al. " Effect of the extract of Annona muricata and Petunia

nyctaginiflora on Herpes simplex virus. J. Ethnopharmacol. 1998; 61(1): 81-3.

Gleye, C., et al. " Cis-monotetrahydrofuran acetogenins from the roots of

Annona muricata 1. J. Nat. Prod. 1998; 61(5): 576-9.

Kim, G. S., et al. " Two new mono-tetrahydrofuran ring acetogenins,

annomuricin E and muricapentocin, from the leaves of Annona muricata. " J. Nat.

Prod. 1998; 61(4): 432-36.

Woo M.H., et al. " Cis-Annonacin and (2,4)-cis-and trans-isoannonacins:

cytotoxic monotetrahydrofuran annonaceous acetogenins from the seeds of Annona

cherimolia. " Arch. Pharm. Res. 1999 Oct;22(5):524-8

Liaw, C. C., et al. " New cytotoxic monotetrahydrofuran Annonaceous

acetogenins from Annona muricata. " J. Nat. Prod. 2002; 65(4): 470-75.

Chang, F. R., et al. " Novel cytotoxic annonaceous acetogenins from Annona

muricata. " J. Nat. Prod. 2001; 64(7): 925-31.

Jaramillo, M. C., et al. " Cytotoxicity and antileishmanial activity of Annona

muricata pericarp. " Fitoterapia 2000; 71(2): 183-6.

Betancur-Galvis, L., et al. " Antitumor and antiviral activity of Colombian

medicinal lant extracts. " Mem. Inst. Oswaldo Cruz 1999; 94(4): 531-35.

Oberlies, N. H., et al. " Structure-activity relationships of diverse

Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma

(MCF-7/Adr) cells. " J. Med. Chem.; 40(13):2102-6 1997

Keinan, E., et al. " Antibody-catalyzed organic and organometallic

transformations and chemical libraries of Annonaceous acetogenins. " The Skaggs

Institute for Chemical Biology Scientific Report 1997-1998.

Zeng, L., et al., " Recent advances in Annonaceous acetogenins. " Nat. Prod

Rep. 1996; 13(4): 275-306.

Anon., Purdue News September 1997; Purdue University, West Lafayette, IN.

http://www.purdue.edu

Feras, Q., et al. " Annonaceous acetogenins: Recent progress. " J. Nat. Prod.

1999; 62(3): 504-540.

Wang, L. Q., et al. " Annonaceous acetogenins from the leaves of Annona

montana. " Bioorg. Med. Chem. 2002; 10(3): 561-65.

Padma, P., et al. " Effect of Annona muricata and Polyalthia cerasoides on

brain neurotransmitters and enzyme monoamine oxidase following cold

immobilization stress. " J. Natural Remedies 2001; 1(2): 144-46.

N'gouemo, P., et al. " Effects of ethanol extract of Annona muricata on

pentylenetetrazol-induced convulsive seizures in mice. " Phytother. Res. 1997;

11(3): 243-45.

 

 

 

The above text has been preprinted from Herbal Secrets of the Rainforest, 2nd

edition, by Leslie Taylor. Published and copyrighted by Sage Press, Inc., © 2002

All rights reserved. No part of this document may be reproduced or transmitted

in any form or by any means, electronic or mechanical, including photocopying,

recording, or by any information storage or retrieval system, including

websites, without written permission from Sage Press, Inc.

 

A complete Technical Data Report is available for this plant

from Sage Press, Inc.

 

 

 

 

 

† The statements contained herein have not been evaluated by the Food and Drug

Administration. The information contained in this plant database file is

intended for education, entertainment and information purposes only. This

information is not intended to be used to diagnose, prescribe or replace proper

medical care. The plant described herein is not intended to treat, cure,

diagnose, mitigate or prevent any disease. Please refer to our Conditions of Use

for using this plant database file and web site.

 

 

 

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