Technical Data Report

for

GRAVIOLA
(Annona muricata)

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Reprinted from The Healing Power of Rainforest Herbs, by Leslie Taylor Published and copyrighted by Square One Pub lishers, Inc, © 2005

GRAVIOLA
Herbal Properties and Actions
Main Actions • kills cancer cells • slows tumor growth • kills bacteria • kills parasites • reduces blood pres sure • lowers heart rate • dilates blood vessels • sedates Other Actions • relieves depression • reduces spasms • kills viruses • reduces fever • expels worms • stimulates digestion • stops convulsions Standard Dosage Leaves Infusion: 1 cup 3 times daily Tincture: 2-4 ml 3 times daily Capsules: 2 g 3 times daily

Fam ily: Annonaceae Genus: Annona Species: muricata Common Names: Graviola, soursop, guanábana, guanábano, guanavana, guanaba, corossol épineux, huanaba, toge-banreisi, durian benggala, nangka blanda, cachiman épineux Parts Used: Leaves, fruit, seeds, bark, roots 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 15–20 cm in diameter and green in color, with 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 graviola in Brazil, guanábana in Spanish-speaking countries, and soursop in the United States. The fruit pulp is excellent for making drinks and sherbets and, though slightly sour-acidic, can be eaten out of hand. TRIBAL AND HERBAL MEDICINE USES 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 a re attributed to the different parts of the tree. Generally, the fruit and fruit juice are taken for worms and parasites, to cool fevers, to increase mo ther’s milk after childbirth, and as an astringent (drying agent) for diarrhea and dysentery. The crushed seeds are used against internal and external parasites, head lice, and worms. The bark, leaves, and roots are considered antispasmodic, hypotensive, and sedative, 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 a lengthy recorded indigenous use. In the Peruvian Andes, a leaf tea is used for catarrh (inflammation of mucous mem branes) 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 W est Indies, the fruit and/or fruit juice is used for fevers, parasites, and diarrhea; the bark or leaf is used as an
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antispasmodic, sedative, and nervine for heart conditions, coughs, flu, difficult childbirth, asthma, hypertension, and parasites. Today, in the United States and Europe, graviola is sold as a popular adjunctive natural therapy for cancer. This use has stemmed from published research on graviola and its naturally occurring chem icals possessing anticancerous actions, rather than its established traditional uses in South America. PLANT CHEMICALS Many active compounds and chemicals have been found in graviola, as scientists have been studying its properties since the 1940s. Most of the research on graviola focuses on a novel set of chemicals called Annonaceous acetogenins. Graviola produces these natural compounds in its leaf and stem, bark, and fruit seeds. Three separate re s e a rch groups have confirmed that these chemicals have significant antitumorous properties and selective toxicity against various types of cancer cells (without harm ing healthy cells). These groups have published eight clinical studies on their findings.1 – 8 Many of the acetogenins have demonstrated selective toxicity to tumor c ells at very low dosages— as little as 1 part per million. Four studies were published in 1998 which further specify the chemicals and acetogenins in graviola that are demonstrating the strongest anticancerous, antitumorous, and antiviral properties.9–12 Annonaceous acetogenins are only found in the Annonaceae family (to which graviola belongs). These chemicals in general have been documented with antitumorous, antiparasitic, insecticidal, and antimicrobial activities.13 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 tum or cells. This is why they are toxic to cancer cells but have no toxicity to healthy cells. Purdue University, in W est 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 Institutes 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 antitum orous and insecticidal properties and uses of these acetogenins. 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.” 14 In several interviews after this information was publicized, the head pharmacologist in Purdue’s research explained how this w orked. 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 main ways that cancer cells develop resistance to chemotherapy drugs is by creating an intercellular pump, which is 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 pum p— 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 multidrug resistant tumors. Purdue researchers reported that the acetogenins preferentially killed multidrug-resistant cancer cells by blocking the transfer of A TP—the chief source of cellular energy— into them.15 A tumor cell needs energy to grow and reproduce, and a great deal more to run its pum p and expel attacking agents. By inhibiting energy to the cell, it can no longer run its pump. W hen acetogenins block AT P ene rgy 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 fourteen different acetogenins tested thus far dem onstrate potent ATP-blocking properties (including several found only in graviola).15 They also reported that thirteen of these fourteen acetogenins tested were more potent against MDR breast cancer cells than all three of the standard drugs (adriamycin, vincristine, and vinblastine) they used
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as controls. The Annonaceous acetogenins discovered in graviola thus far include: annocatalin, annohexocin, annom onicin, annomontacin, annomuricatin A and B, annomuricin A through E, annom utacin, annonacin, annonacinone, annopentocin A through C, cis-annonacin, ciscorossolone, cohibin A through D , corepoxylone, coronin, corossolin, corossolone, donhexocin, epomuricenin A and B, gigantetrocin, gigantetrocin Aand B, gigantetrocinone, gigantetronenin, goniothalamicin, iso-annonacin, javoricin, montanacin, montecristin, muracin A through G, muricapentocin, muricatalicin, muricatalin, muri-catenol, muricatetrocin A and B muricatin D, muricatocin A through C muricin H, muricin I, muricoreacin, murihexocin 3, murihexocin A through C, murihexol, murisolin, robustocin, rolliniastatin 1 & 2, saba-delin, solam in, uvariamicin I and IV, and xylom aticin. BIOLOGICAL ACTIVITIES AND CLINICAL RESEARCH In a 1976 plant screening program by the National Cancer Institute, graviola leaves and stem showed active toxicity against cancer cells, and researchers have been following up on these findings since.16 Thus far, specific acetogenins in graviola and/or extracts of graviola have been reported to be selectively toxic in vitro to these types of tumor cells: lung carcinoma cell lines;1,3–6 human breast solid tumor lines;4 prostate adenocarcinoma ; 9 pancreatic carcinoma cell lines;1, 9 ,12 colon adenocarcinoma cell lines;1, 2, 12 liver cancer cell lines;17–20 human lymphoma cell lines; 21 and multi-drug-resistant human breast adenocarcinoma.22 Researchers in Taiwan reported in 2003 that the main graviola acetogenin, annonacin ,was highly toxic to ovarian, cervical, breast, bladder and skin cancer cell lines at very low dosages, saying “annonacin is a prom ising anti-cancer agent and worthy of further anim al studies and, we would hope, clinical trials.”23 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. First they inoculated m ice with lung cancer cells. Then, one third received nothing (the control group), 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 percent reduction of tumor mass over the control group—but 50 percent 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 percent—slightly better than adriamycin— and w ithout 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.”24 Other studies over the years have validated some of graviola’s other uses in herbal medicine. Several early studies demonstrated that the bark as well as the leaves had hypotensive, antispasmodic, anticonvulsant, vasodilator, smooth-muscle relaxant, and cardiodepressant activities in animals.25, 26 Researchers verified graviola leaf’s hypotensive properties in rats again in 1991.27 Several studies over the years have demonstrated that leaf, bark, root, stem, and seed extracts of graviola are antibacterial in vitro against numerous pathogens,28–30 and that the bark has antifungal properties.30,31 Graviola seeds demonstrated active antiparasitic properties in a 1991 study, which validated its long standing traditional use,3 2 and a leaf extract showed to be active against malaria in two other studies (in 1990 and 1993).33,34 The leaves, root, and seeds of graviola demonstrated insecticidal properties, with the seeds demonstrating strong insecticidal activity in an early 1940 study.35 In a 1997 clinical study, novel alkaloids found in graviola fruit exhibited antidepressive effects in animals.36 Current Practical Uses Cancer research is ongoing on these important Annona plants and plant chemicals, as several pharmaceutical companies and universities continue to research, test, patent, and attem pt to
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W ith graviola. W ith the demise of the world’s tropical rainforests.) Thus far. different alkaloid chemicals in the seeds and roots have shown some prelim inary in vitro neurotoxic effects. and are now offered under several d ifferent manufacturer’s labels in health food stores. market. Now that scientists have the ability to recreate this chem ical and several other active acetogenins in the laboratory. which thwarted earlier attempts. Graviola products (capsules and tinctures) are becom ing more widely available in the U. combining it with other supplem ents and natural products that increase or enhance cellular ATP may reduce the effect of graviola. Like the developm ent of taxol. using the seeds and root of graviola is not recommended at this time.S. they lose much of the antitumorous actions. as happened with taxol) to be able to m ake this promising therapy available to cancer patients in a timely fashion. After all. which can be patented and turned into a new (patented) cancer drug. the next step is to change the chemical just enough (w ithout losing any of the antitumorous actions in the process) to become a novel chemical. annonacin. These acetogenin chemicals have a unique waxy center and other unique molecular energy properties. Graviola is certainly a promising natural remedy and one that again emphasizes the importance of preserving our remaining rainforest ecosystems. universities.” 15 4 . One researcher studying graviola summarized this idea eloquently: “At the time of preparation of this current review. (which offers just as high of an am ount of acetogenins as the root and almost as much as the seed) is reported to be 2–3 g taken three or four times daily. graviola seems to be following the same path as another well-known cancer drug—Taxol. is lost. In fact. and at least one major pharmaceutical company gave up in the process. As one of graviola’s mechanisms of action is to deplete ATP energy to cancer cells. In the meantime. scientists seem to be thwarted again—every time they change the chemical enough to be patentable. over 350 Annonaceous acetogenins have been isolated from 37 species. 36 Therefore. From the time researchers first discovered an antitumorous effect in the bark of the pacific yew tree and a novel chemical called taxol was discovered in its bark. thus. this class of compounds can be expected to continue to grow at an exponential rate in the future. are significantly bioactive and are worthy of fractionation. contained within these endangered species. including annonacin) as a complem entary therapy to their cancer protocols. provided that financial support for such research efforts can be found. (Naturally occurring plant chemicals cannot be patented.35 Researchers have suggested that these alkaloids might be linked to atypical Parkinson’s disease in countries where the seeds are employed as a com mon herbal parasite remedy. The therapeutic dosage of graviola leaf. and government agencies before the first FDA-approved Taxol drug was sold to a cancer patient (which was based on the natural taxol chemical they found in the tree bark). The main supplement that increases ATP is a common antioxidant called Coenzyme Q10 and for this reason. Our preliminary efforts show that about 50% . it has taken researchers almost ten years to successfully synthesize (chemically re p roduce) the main antitumorous chemical. such work is compelling before the great chem ical diversity. it took thirty years of research by numerous pharmaceutical companies. it m ay w ell take government agencies like the National Cancer Institute and the National Institutes of Health to step forward and launch full-scale human cancer research on the synthesized unpatentable natural plant chemical (which will allow any pharmaceutical company to develop a cancer drug utilizing the research.synthesize these chemicals into new chemotherapeutic drugs. it should be avoided when taking graviola. While research confirms that these antitumorous acetogenins also occur in high amounts in the fruit seeds and roots of graviola. graviola has had a long history of safe use as an herbal remedy for other conditions for many years. Perhaps—if enough people believe that the possible cure for cancer truly is locked away in a rainforest plant—we will take the steps needed to protect our remaining rainforests from destruction. and research indicates that the antitumorous acetogenins are selectively toxic to just cancer cells and not healthy cells—and in minuscule amounts. many cancer patients and health practitioners are not w aiting— they are adding the natural leaf and stem of graviola (with over forty docum ented naturally occurring acetogenins. of over 80 Annonaceous species screened.

Graviola has demonstrated significant in vitro antimicrobial properties. at a dosage of 300 mg/kg. Drug Interactions None have been reported. parasites. intestinal colic. dysentery. nervousness. See contraindications above. Contraindications Graviola has demonstrated uterine stimulant activity in an animal study (rats) and should therefore not be used during pregnancy. neuralgia. heart conditions. rash. vasodilator.Traditional Preparation The therapeutic dosage is reported to be 2 g. and as a lactation aid and sedative Brazil Caribbean Curaçao Haiti Jamaica 5 . in capsules or tablets. nervousness. spasms. and as a sedative and tranquilizer for coughs. and monomine oxidase activity. liver problems. sores. intestinal parasites. parasites. nervousness. fever. weakness. nervousness. Chronic. gallbladder problems. skin disease. norepinephrine. nerves. People taking antihypertensive drugs should check with their doctors before taking graviola and m onitor their blood pressure accordingly (as medications m ay need adjusting). palpitations. digestive sluggishness. fever. One study with rats given a stem-bark extract intragastrically (at 100 mg/kg) reported an increase in dopamine. edema. worms. spasms. bronchitis. three tim es daily.39 Alcohol extracts of graviola leaf showed no toxicity or side effects in mice at 100 mg/kg. however. spasms. diarrhea. wounds. heart conditions. spasms. pain. hypertension. and cardiodepressant activities in animal studies and is contraindicated for people with low blood pressure. Supplementing the diet with probiotics is advisable if this plant is used chronically. pain. a reduction in explorative behavior and mild abdominal constrictions were observed. Taking graviola in combination with Coenzyme Q10 and other agents that increase cellular ATP energy may reduce the effects of graviola. weakness. water retention. cough. worms for chills. flu. lice. chest problems. fever. parasites. however. rheumatism. flu. and as a sedative for childbirth. fevers. Graviola has demonstrated hypotensive. reduce the amount used. and as a lactation aid and sedative for asthma. A standard infusion (1 cup three times daily ) or a 4:1 standard tincture (2–4 ml three times daily) can be substituted if desired. graviola may potentiate antihypertensive and cardiac depressant drugs. diabetes. as well as an inhibition of serotonin release in stress-induced rats.40 If sedation or sleepiness occurs. Worldwide Ethnomedical Uses Region Uses for abscesses. indigestion. long-term use of this plant may lead to the death of friendly bacteria in the digestive tract due to its antimicrobial properties. pellagra. diarrhea.

” J. hypertension. et al. high blood pressure. and as a sedative for blood cleansing. ringworms . “Bioactive single-ring acetogenins from seed extracts of Annona muricata. as thma. fainting.html 15.” J. from the leaves of Annona muricata.. scurvy. scurvy. ringworm. F. Prod. et al. and to reduce bleeding for diarrhea. et al. Nat. J. Anon. dyspepsia. Prod. 2. from the leaves of Annona muricata. and to reduce bleeding for chest colds. Kim. fever. W u. worms for diabetes. 58(6): 909–15. Prod. hypertension. 8. and as a lactation aid for arthritis.purdue. G. “Muricatocins A and B. West Lafayette. Nat. kidney.edu/UNS/newsandphotos.. liver disorders. worms. W u. annomuricin E and muricapentoc in.” J. E. childbirth. dermatos is. 62(3): 504-540. dysentery. Prod. annomutacin and (2. dysentery.. 1998. 1995. from the leaves of Annona muricata. spasms. 6. diarrhea. indigestion. 49(2): 565–71. 58(9): 1430–37. M. G. intestinal parasites.” Planta Med. lice. Prod . IN. F. http://www. 3. Prod. diarrhea.” J.. Rieser. two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata. 1995. stomach problems. palpitations. insomnia. 5. 61(4): 432–36.” J. ulcers(internal). 1996 . 9. 58(6): 902–8. “Muricatacin: a simple biologically active acetogenin derivative from the seeds of Annona muricata (Annonac eae)” Tetrahedron Lett.. Prod. et al. W u.. Ethnopharmacol . et al. parasites. from the leaves of Annona muricata.. fever. diarrhea. 12. “Two new mono-tetrahydrofuran ring acetogenins. et al. 14. 32(9): 1137–40. J. “Cis-monotetrahydrofuran ac etogenins from the roots of Annona muricata 1. and as a lactation aid and sedative Malaysia Mexico Panama Peru Trinidad United States West Indies Elsew here Footnotes 1. et al. 61(1): 81–3.. Nat. coughs. dysentery. 1999. 59(2): 100–8. 1991. 4.. 61(5): 576–9. 10. parasites. L.. and as a lactation aid for cancer. 59(11): 1035–42. heart problems. E. “Additional bioactive acetogenins. “Annonac eous acetogenins: Rec ent progress . stomach ulcers. J.” J. 6 . “Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata. Nat. Phytochem istry 1998. Q. fungal infections. et al. malaria. Keinan. 1995. 1998. et al. 1996.. 1995. E.. mono-tetrahydrofuran acetogenins. 58(6): 830–36. S. Nat. annomuricins A and B. Prod. et al. 59(1): 91–2. 1998.. F. et al. Nat. childbirth. kidney problems. E. hypertension. tumors for asthma. annomuricin C and muricatocin C. “Antibody-catalyzed organic and organometallic transformations and chemical libraries of A nnonaceous acetogenins. Purdue News September 1997. F.. “New bioactive monotetrahydrofuran Annonaceous acetogenins. Gleye. lice.4-trans and cis)-10Rannonacin-A-ones. S. rheumatism. Purdue University. Nat. ringworm. Kim. bile insufficiency. 7. from the leaves of Annona muricata. 11. M. flu. Rieser. J. tumors. J. liver disorders.” J. W u. diarrhea. depression. Padm a. et al. Nat. diarrhea.Region Uses for boils. C. inflammation. pain. fever. Zeng.” J. E. P.” The Skaggs Institute for Chem ical Biology Scientific Report 1997–1998. Rieser. 13. cancer. “Five new m onotetrahydrofuran ring acetogenins from the leaves of Annona muricata. Feras. hypertension. “Muricoreacin and murihexocin C. M. Prod. 1993. et al. “Two new cytotoxic monotetrahydrofuran Annonaceous acetogenins.. “Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus. Nat. et al.

40.. M. Indie.. “Preliminary screening of antibacterial and antitumor activities of Papua New Guinean native medicinal plants. a mono-tetrahydrofuran acetogenin.” Int. Tattersfield. Trop. et al. Gbeassor.” Rev. “Pharmacological screening of plant decoctions comm only used in Cuban folk medicine. F. P. 17. 1991. T. P. et al. 94(4): 531-35. Chang. et al. A . “Plant extracts with cytostatic properties grow ing in Cuba.” J. “Pharmac ological screening of some W est Indian medicinal plants. 71(2): 183–6. et al. Chem .” Bioorg. Disord. 1997. Ned. 1992. E thnopharmacol.” Fitoterapia 2000.” Mem. N’gouemo. H. et al. Inst. University of Illinois. 2002. E thnopharmacol. 1993. Sundarrao. et al.and caspase-3-related pathw ay. 354(9175): 281-6. 31(2): 97–104. 10(3): 561-65. 14: 556–61... K. J. Feng. 57(5): 434–36. 49(11): 1145–49. 31(4): 255–58.” Phytother. Nicolas. Prod. 33(1/2): 21–4. IV . S. Padm a. 20. 1941. 1997. 1: 84-90. Jaramillo. 18.. 37. 21. arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax. C. Pharmacog. “Annonaceous acetogenins from the leaves of Annona montana. et al. Med. 1962. Nat. 8(6): 64. S. “Effect of Annona muricata and Polyalthia cerasoides on brain neurotransmitters and enzyme monoamine oxidase following cold immobilization stress. 30. Lopez. Caribbean P arkinsonism Study Group. C. Oswaldo Cruz 1999. P harm . Med. J. 40(13): 2102–6. “Possible relation of atypical parkinsonism in the French W est Indies with consumption of tropical plants: a case-control study. Cubana Med. Cubana Med. Abraham A. W ang. 1940. B iol.” Ing. 65(4): 470–75... Nat Cancer Inst Central Files (1976). 38. “Effects of ethanol extract of Annona muricata on pentylenetetrazol-induced convulsive seizures in mice. Betancur-Galvis. Life Sci. 35. M. Trop. et al. Meyer. et al. J. 31. M .” J.16..” Planta Med. et al. Pharmacol.. Antoun. “Novel cytotoxic annonaceous acetogenins from Annona muricata. “In vitro antimalarial activity of six medicinal plants. M .. L. Chang.” Phytother. 4(3): 115–17. Pharmacog. C. 1995. 72(25): 2853-61. Misas. 19. A . M. 64(7): 925–31. 24. F. Bories. 23. “New cytotoxic monotetrahydrofuran Annonaceous acetogenins from Annona muricata. Natural Remedies 2001. 31(1): 3–6. Yuan.. “New Adjacent Bis-Tetrahydrofuran Annonaceous Acetogenins from Annona muricata .. D. “The alkaloids of Annona muricata. 36(1): 81–5. 26. Pharm.. et al. 1993. Carbajal.” J. Lancet. Caparros-Lefebvre. 28. D. 33. From NAPRA LERT Files. R. J. 36. Lannuzel. “Antiparasitic activity of Annona muricata and Annona cherimolia seeds. “Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe. et al. “Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells. Nat. 1979.. Unpublished data. I. F. Liaw. Prod.. 34.. 2003.” Mov.. Pharmacol. 1990. et al. 22. L. 2002. 2003 May 9.” J. 25. et al. 1997.. et al.. 27. P.” J. 7 . 11(3): 243–45. National Cancer Institute.” J. 2002. 32.” Int. R. et al. “Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HT ergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products. Q.” Ann.” J. 31(1): 29–35. “Contribution to the biological evaluation of Cuban plants. 2001.. et al. Res. 1979. “Annonacin.” Rev. “Antitumor and antiviral activity of Colombian medicinal plant extracts. 39. A.. “Cytotoxicity and antileishmanial activity of Annona muricata pericarp. Res. et al. C. "Screening of the flora of P uerto Rico for potential antimalarial bioactives . D. C. M. “The insecticidal properties of certain species of Annona and an Indian strain of Mundulea sericea (Supli). Chem . 29. Anon. 27: 262–73. 1(2): 144–46. 69(3): 241-6. et al. Heinrich. et al. C.” J. Appl.” Planta Med. 1999 Jul 24. et al. et al.. Hasrat. “Parasitological and microbiological evaluation of Mixe Indian medicinal plants (Mexico). 1991.

A. cough. A. 2 nd edition) Other Common Names: Graviola.9 Curacao. lactogogue.12 Guam. colic. December 2003 Fam ily: Annonaceae Synonyms: Annona macrocarpa. The fruit is popular in S outh Am erica. liver disorders. carminative. parasites. bronchitis. sedative.D. rheumatism. fevers. 2 nd edition) Additional Common Names: Graviola Portuguese Huanaba Spanish Guanábana Spanish Toge-Banreisi Taiwanese Guanábano Spanish Durian benggala Indian Guanavana Spanish Nangka blanda Indian Guanaba Spanish Cachim an épineux French Corossol French Sauersack German Epineux French Stachelannone German Overview Botanical Description Graviola is a small. glossy.15.20. anticonvulsant and digestive.17. spasms.14 Haiti. worms. tonic. head lice. skin disorders. Seeds: Astringent. gallbladder disorders. spasms. 8 . ulcers. antipyretic. styptic. heart.3 Brazil. hypertension. upright tropical evergreen tree.26 Suriname. diabetes. diabetesgrippe. Bark: Asthenia.North Am erican (Herbs of Commerce. childbirth. heart tonic. tumors.30 Summary of Traditional Uses of Graviola:31 Flower Fruit: Bronchitis. worms.21 Peru. with large. emetic. asthenia. Leaf: Abscesses. edema. The traditional use of graviola has been recorded in herbal medicine systems in the following countries: Amazonia. arthritis pain. Ethnobotanical Uses All parts of the graviola tree have been used medicinally in traditional herbal medicine. dysentery. skin parasites. dysentery. cough. 5-6 m high. neuralgia. ringworm. juice. It produces a large. spasms. diarrhea. indigestion. insecticide.13 Guyana. hydropsy. parturition. antispasmodic. 27 Togo 28 and W est Indies. guanábana (Herbs of Comm erce. nervine. is yellowgreen in color and has white flesh inside. intestinal worms. Rootbark Calmative. 2 Borneo. palpitations. nervine. cough. asthma. sedative. antiparasitic. tranquilizer.18 Madagascar. Traditional herbal medicine practitioners have attributed graviola with the following properties and actions: anthelmintic. BHSc. diuretic. bonplandiana. cearensis.10 Dominica.Graviola Annona muricata MONOGRAPH By Barbara Noller N.. Colitis. Root: Diabetes. lactogogue. mouth sores. malaria. spasms. edible fruit that is 15-23 cm in diameter. hypertension. grippe.29.11 Guatemala. diabetes. asthma. parasites. sedative. 19 Malaysia.4-8 Cook Islands.1 Barbados. infections. catarrh. Guanabanus muricatus Standard Common Name: Soursop .22. hypotensive. dark green leaves. parasites. fever.16 Jamaica. tranquilizer. parasites. heart-shaped. nervousness. nervine. rashes. sedative. astringent.

44 • Human tumor multidrug-resistant SW 480 (P-glycoprotein+. Following are select in vitro studies w here acetogenins were utilized against various cell lines: • Hum an hepatom a hep G(2).9% inhibition was seen. 15 cell lines. muricatalicin. muricoreacin. donhexocin. muricatalin. 2.24 It has also been used in som e herbal m edicine systems for its sedative and antispasmodic properties.33. annomutacin. annomontacin.43 • Human breast adenocarcinoma MD A-MB231 and carcinoma MCF-7. stem. 2.42.42.30. epomuricenin A & B. Pgp+) tumor cells.44 • Various cancer cell lines. m uricatocin A thru C muricin H. gigantetronenin.5 mcg/ml was seen in one study. corossolin. annonacin. bark and seeds of graviola contain varying amounts of a novel group of chemcials believed to be biologically active.32. gigantetrocin A & B.39. The annonaceous acetogenins in graviola include: annocatalin. murihexocin 3. gigantetrocin. called Annonaceous acetogenins. xylomaticin. coronin.35-38 • Six human tumor cell lines. muricin I. annomonicin. 31 Various acetogenins in graviola have been documented with the following biological activity: In vivo Cytotoxic Activity 10 mg/kg of annonacin was given intraperitoneally in mice with Lewis lung cancer. 22. N on-adriam ycin resistant tumor cells. uvariam icin I & IV. solamin. cohibin A thru D. annonacinone. montecristin. cis-corossolone. muracin A thru G.40 • Pancreatic carcinoma PACA-2. rolliniastatin 1 & 2. muricapentocin. javoricin.39.39-41 • Prostate adenocarcinoma PC-3. corepoxylone. growth was inhibited 50% at concentrations of <10-12 ug/ml. 46 • Adriam ycin resistant tum or cells (M 17/adr breast cancer cells). The leaf.47 • Annonacin was able to kill various cancer cell lines at an IC50=<4 ug/mL.44 • Human colon cancer HT-29. iso-annonacin. muricatetrocin A & B m uricatin D. cis-annonacin. corossolone. annohexocin. murihexol.40. murisolin.25.24 Chemistry Phytochem ically graviola is rich in miscellaneous lactones and isoquinoline alkaloids. A CC50=49. muri-catenol. robustocin. annopentocin A thru C .40 • Murine leukemia L1210 and P388 leukemia. goniothalamicin. annomuricin A thru E. 48 9 .Primary Uses in Traditional Herbal Medicine Systems Internal Graviola is prim arily em ployed in traditional herbal m edicine systems for parasitic infections and cancer. annomuricatin A & B. sabadelin. a 57. gigantetrocinone. m ontanacin. 34 In vitro Cytotoxic Activity In vitro studies are numerous. murihexocin A thru C.45 • Human lung carcinoma A-549.

67 mcg/ml seen. Annonacin also reduced the survival of non-dopaminergic neurons. It had an ED50 of 0. Toxic effects were seen at lower concentrations when incubation time was extended over several days. w as attenuated by increasing the concentration of glucose in the culture. ED50=1. annonacin.3 mcg/ml of coreximine or 100 mcg/ml reticuline. W ithdrawal of the toxin after short-term exposure arrested cell death. 3. seed. IC50=0. ED50=<20 m cg/ml.9 mcg/ml. IC50=2 m cg/ml. was added to mesencephalic cultures for 24 hours. GABAergic neurons were also affected. 50 Chronic exposure to these alkaloids may be an etiological factor in atypical Parkinson’s disease.018 microM. sanborni.59 • Leaf & twig showed activity against human tumor cell lines. killing dopaminergic neurons. M.43. N euronal death.49 Neurological Activity In a 2002 study cultured mesencephalic dopaminergic neurons were exposed to total alkaloids from graviola rootbark. decemlineata. After 24 hours 50% of dopaminergic neurons degenerated with 18 mcg/ml of total extract. ethyl acetate and methanol extract showed activity against human histiocytic lymphoma U-937. GABA uptake was not affected.51 In a recent 2003 study one of the main acetogenins in graviola. 58 • Hexane.43. stem and bark have all been documented with in vitro cytotoxic activity utilising various extracts including ethanol and water: • Ethanol leaf extract showed activity against human hepatoma hep G 2. persicae. along with the presence of annonacin. prevented neuronal death.37 • Leaf extract showed activity against human kidney carcinoma CA-A498.2.32 • Ethanol leaf extract showed activity against bovine kidney cell line MDBK. occurring by apoptosis.15. L.51 Insecticidal The acetogenins (such as squam ocin) have shown activity against the follow ing insects: M. 57 • Ethanol leaf & stem extract showed activity against human oral epidermoid carcinoma CA9KB. 52 Acute treatm ent of m esencephalic dopaminergic neurons and GABA neurons in vitro with a rootbark extract of coreximine or reticuline reversibly inhibited dopamine uptake w ithout causing neuronal death. Increasing glucose or mannose concentrations.53-55 In vivo and In vitro Research and Pharmacological Actions Anticancerous Activity Cytotoxic Activity The leaf. or two of the most abundant alkaloids coreximine and reticuline. Toxin withdrawal after short-term exposure arrested cell death.49 10 . Blatella germanica.56 • Ethanol leaf extract showed activity against human breast carcinoma MCF-7.33 Cytostatic Activity The leaf inhibited tumor cell growth including adriamycin resistant human mammary adenocarcinoma MCF-7/Adr cells in vitro . 4.Cytostatic Activity Acetogenins have shown inhibition of tumor cell growth towards adriamycin resistant human mam mary adenocarcinoma MC F-7/Adr cells.

hexane and ethyl acetate extracts of the seed.033 ml/L had uterine stimulant activity. L.10 ± 0. 2.63 This activity may be due to the in vivo hypotensive activity of the leaf and stem. M.69 11 .25 Monoamine o xid ase un its/m g prote in 5.82 ± 13. One hour after adm inistering the extract the rats were stressed by cold im mobilization (placing anim als in a restrainer for 3 hours at 4 /C).38 ± 59.66 930.63 mcg/ml.34.34* 892. demonstrated through the in vitro anticrustacean assay system.37 8.2m l/L of a w ater extract had the same effect. leaf and seed have shown serotonin receptor binding activity in vitro .72 588.43 ± 19.28.99 ± 22. 62 Neurological Activity 100 mg/kg of an ethanol leaf extract given intraperitoneally to mice had anticonvulsant activity.30 ± 29.10 ± 67.61 Uterine Stimulant Activity W ater and ethanol extracts fed orally to rats at 0.53 731. stem.32 * p<0. salina.76 ± 22. In rabbits an ethanol extract at 3.24 5-Hydroxy Indoleace tic acid (n g/g m ) 533.01 compared to restraint control Antimicrobial and Antiprotozoal Activity Antiparasitic Methanol.24 ± 47. N. Following is the effect of graviola on brain neurotransmitters versus controls:67 Treatment Group Noradrenaline (n g/g m ) D op am in e (n g/g m ) 5Hydroxytryptamine (n g/g m ) 679.68 Antimalarial Ethanol leaf extracts have shown in vitro antim alarial activity against Plasmodium falciparum D6 & W -2 at IC50=20 .99 ± 62.61 The leaf had an LC50=0.12 402. L.62 Card ioactive and H ypoten sive Activity In one study 1 ml/L water extract of the leaf fed intravenously to rats resulted in a reduction in blood pressure by more than 30%.60. bark and pericarp have demonstrated in vitro antiparasitic activity against E.64 Antispasmodic and Muscle Relaxant Activity Ethanol and water extracts of the leaf and stem fed at 0. Leishmania trypansoma .65 Extracts of the fruit. dessetae.17 mcg/ml.033 ml/L to guinea pigs had antispasmodic activity.15 Normal Control Restraint Control Graviola treated 445.19 588. 3. braziliensis.19 699.59.00 ± 0.62 A water extract of the bark exhibited a cardiodepressant effect in rabbits.Antitum or Activity Ethanol and chloroform extracts of the seed and leaf have shown antitumor activity in vitro .28 4.24 ± 0.53 750.22 ± 59.53 376. histolytic. panamensis and L.02 ± 32. promastigotes.3 ml/L relaxed smooth m uscle. A.66 Alcoholic extracts of the stembark was administered to rats intragastrically at 100 mg/kg.77 ± 72. brasiliensis.

aeruginosa. flexneri. while the root had activity against herpes simplex type 2 in vitro at CC50 and EC 50=0.46.97-20. spp. methanol and ethanol extracts have demonstrated in vitro antibacterial activity at concentrations of 2-3 m cg/plate to 1 m g/disc. marcescens. coli. S. P. persicae. sanborni.76 Antioxidant Activity Stem and bark ethanol extracts at 100 mg/kg intragastrically in rats had antioxidant activity.38. 73 The stem and bark in an ethanol extract at 1 mg/ml had in vitro activity against herpes simplex 1.26 ppm. acetone. 6. S.79. S.78 Patents Pending / Filed Num erous patents have been filed on various acetogenins w hich are found in graviola and other plant members of the Annonaceae family. By inhibiting this enzyme cellular ATP is depleted. bark and leaf ethanol extracts have demonstrated in vitro activity against B. S. stem and bark water. newport. Organisms the extracts are active against include: E.Antibacterial Leaf.53-55 Antiulcer Activity Stem and bark ethanol extracts at 100 mg/kg intragastrically in rats had antiulcer activity.77 Antihepatotoxic Activity A leaf decoction reduced ASAT leakage by hepatocytes in vitro at 1 mg/plate. This enzyme is only transiently expressed in ‘normal healthy’ cells. glabrata at LD50-0. Mechanism of Action Anticancerous Activity Cytotoxic Activity Anticancerous and cytotoxic effects of graviola are attributed to the annonaceous acetogenins which have a number of mechanisms including: • Inhibition of NADH oxidase in the plasma m embranes of cancer cells. albus. aureus. S.70-72 Antiviral A water soluble fraction from the stem had an antiproliferative effect on HIV-infected cells in vitro at IC50=<2mcg/ml. Blatella germanica. S. subtilis. B.5 mcg/ml. L..75 Insecticidal The leaf had activity against the following insects in vitro : M. decemlineata. M.80 • Inhibition of complex I (NADH:ubiquinone oxidoreductase) in mitochondrial electron 12 .74 Molluscicidal Stem.

which are mitochondrial respiratory chain complex I inhibitors. inhibiting oxidative phosphorylation and resulting in lower ATP levels. Deprivation of the cancer cells ATP results in apoptosis of the cancer cell. Antimicrobial Activity Graviola has insecticidal activity which is attributed to the acetogenins.80 Neurological Activity Antidepressant.46.67 The potential neurotoxic effect of the seeds. helping the organism cope better during stress. Two intracellular ATP-binding sites are found on P-glycoprotein. Increased expression of a plasma membrane pump. The acetogenins. It also decreases MAO (monoamine oxidase) activity which leads to increases in 5-HT and 5-HIAA levels.46. It w as concluded that graviola had a normalizing effect in rats against a variety of stressors. through depletion of AT P. Pest ingestion of the acetogenins produces mortality in both susceptible and insecticidal/pesticidal-resistant cockroaches. Pre-treatment with graviola prevented the stress-induced depletion of norepinephrine and dopamine. indicating it had adaptogenic potential. sedative and tranquilizing properties of graviola may be due to the ability of certain alkaloids to have agonistic properties towards 5-HT1A receptors in calf hippocampus. In addition pretreatm ent with graviola reduced the stress-induced rise in brain 5-HT and 5-HIAA.48 • The acetogenin annonacin is able to induce apoptotic cell death.85 Cold imm obilization stress in rats causes depletion of norepinephrine and dopamine levels in the brain. were enhanced by annonacin.48 Through the above mechanisms of action the acetogenins are able to decrease oxidative phosphorylation and cytosolic ATP production. cell cycle checkpoint proteins. and increased MAO activity.83 Overall Activity The activity of graviola is mainly attributed to the acetogenins. In addition p53 and p21. Annonacin is able to arrest the cell cycle in the G1 phase. is a contributor to multidrug resistance. and inhibit the S phase progression. They are suggested for use in the control of insect pests such as cockroaches. hence inhibiting cancer cell growth. root and rootbark is discussed under Chemicals.52 13 . can reduce the activity or shut down the P-glycoprotein pump. The pump ensures elimination of the anticancer compound before it can have its effect on the cancer cell.transport systems. The effectiveness of the acetogenins against insecticial/pesticidal-resistant insects suggests that pesticide-resistance is associated with ATP-dependent factors. 46. It enhanced the expression of Bax and Bad. and the pump activity requires ATP. but not Bcl-2 or Bcl-xL.84 • Cancer cells at the S phase of their cell cycle are more vulnerable to the acetogenin annonacin. P-glycoprotein.80.46.80-83 • Inhibition of cancer cells that are multidrug resistant.

63.50 Excessive consumption of these parts of the plant should be 14 . 46.64 It may potentiate antidepressant drugs and interfere with MAO -inhibitor drugs. vasodilator. covered. 3 times daily between meals Tincture: Of a 1:2 tincture take 2-4 ml three times daily Duration of Administration Internal Long-term administration (6 months) with no health complaint may deplete healthy cells of ATP. Contraindications Pregnancy and Lactation: Graviola has documented uterine stimulant activity in an animal study (rats) and should not be used during pregnancy. Alcohol extracts of graviola leaf showed no toxicity or side effects in mice at 100 mg/kg intraperitoneally.Dosage Internal Crude Preparations.31 Safety Rating Not rated. Coenzyme Q10 is required for the function of the ubiquinone oxidoreductase. and cardiodepressant activities in animal studies and is contraindicated for people with low blood pressure. In vitro studies show they cause DNA dam age and apoptosis of dopaminergic cells and GABAergic neurons. root and seed of graviola have been linked to a levodopa-resistant parkinsonism. a reduction in explorative behavior and mild abdominal constrictions was observed.62 Graviola has demonstrated hypotensive.66. for 5-10 minutes.67 Co-enzyme Q10 may reduce the activity of graviola. Leaf and Stem 2 grams three times daily Infusion: 1 cup (150 ml) boiling water poured over approximately 2 grams of dried leaf and stem and steep.80-83 Side Effects Graviola has demonstrated emetic properties in one animal study with pigs. Large single dosages may cause nausea or vomiting. Duration of adm inistration varies per complaint and individual.65 Alkaloids in the rootbark. how ever. which graviola has been shown to inhibit. at a dosage of 300 mg/kg.63 Drug Interactions Graviola may potentiate antihypertensive and cardiac depressant drugs.

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and bronchitis. cough. Decoction drunk for gallbladder trouble. edema. Used to treat skin rashes. Typ e Extract / Route Infusion Oral Dried Oral Hot H2O Ext Oral Leaves External Decoction Oral Juice Oral Hot H2O Ext Oral Infusion Oral Maceration External Hot H2O Ext Oral Maceration External Decoction Oral Not stated Used For Human A dult Human A dult Human Adult Human Adult Human A dult Human A dult Human Human Human Human Human Human A dult Adult A dult A dult A dult A dult Ref # ZZ1005 ZZ1005 T05032 K27823 ZZ1072 ZZ1072 ZZ1024 L15585 ZZ1002 ZZ1072 ZZ1072 ZZ1099 ZZ1099 Leaf + Shoot + Flower Brazil Seed B razil Rootbark B razil Leaf Cook Islands Used for cough and chest problems. Used as a carminative. and antidiabetic. for dysentery. as an anthelmintic and antirheumatic. for abscesses. Used as a sedative. antispasmodic. Human A dult Considered emetic and astringent. Used Used Used Used Used Used for liver problems. Tea is drunk by women in labor (parturition). skin diseases. for spasms. Tea used by asthma sufferers. arthritis pain and as an antiparasitic. Used for nervousness. Used for the spleen and for fever. and skin infections. fever and hydropsy. and chest problems. cough. Tea used as a sedative and heart tonic. diarrhea. Used for ringworm. Used to treat indigestion. for neuralgia. rheumatism.Ethnomedical Information for Graviola (Annona muricata) Part / Location Leaf Amazonia Seed A mazonia Leaf Barbados Leaf Borneo Flower + B ud Brazil Fruit Brazil Leaf Brazil Documented Ethnom edical Use Used as a strong diuretic for swollen feet (edema) and as a tonic. mouth sores . rheumatism. Used for dysentery. Considered calmative. Not stated Decoction Oral Decoction External Decoction Oral Hot H2O Ext Oral Human A dult Human A dult Human A dult Human A dult Human A dult ZZ1099 ZZ1099 K20471 Leaf Curacao A05332 Leaf Dominica Leaf Guatemala Leaf Guam Leaf Guyana Hot H2O Ext Oral Hot H2O Ext Oral Hot H2O Ext Oral Hot H2O Ext Oral Human (pregnant) Human A dult Human A dult Human A dult A01962 M27151 W 01267 ZZ1033 19 . intestinal colic. Used for bronchitis and resistant coughs.

asthma. Fruit Oral Human A dult ZZ1020 Leaf Jamaica Infusion used as an antispasmodic. parasites. sedative. asthenia. sedative. Used for indigestion and catarrh. Used to treat catarrh. asthenia. Used as an antispasmodic. hypertension. grippe. Used as an astringent and a styptic. and asthenia. diarrhea. Used for grippe. parasites. internal ulcers. and grippe. diarrhea and as a lactogogue. and nervine for heart conditions. coughs. sedative. hypertension and parasites. hypertension. and parasites. difficult childbirth. fortifies the intestinal flora and reduces inflammation. Used for fevers. diarrhea and as a lactogogue. Used for heart conditions. Used as an antispasmodic. Beverage prepared as a lactagogue.Part / Location Bark Guyana Fruit Haiti Leaf Haiti Documented Ethnom edical Use Tea used as a sedative and heart tonic. fevers. grippe. coughs. Used as an antispasmodic. Used as a sedative and antispasmodic. coughs. diabetes. liver disorders. Reduces inflammation of the colon. and nervine. coughs. sores. Used for indigestion and catarrh. Typ e Extract / Route Hot H2O Ext Oral Fruit Oral Not stated Decoction Oral Decoction Oral Used For Human A dult Human A dult Human A dult Human A dult Human A dult Ref # ZZ1033 AA1008 AA1008 T13846 AA1008 Bark Haiti Fruit Jamaica Used for fevers. Used for high blood pressure and diarrhea. liver maladies and malaria. difficult childbirth. and nervine for heart conditions. dysentery. Used to tranquilize the nervous system and digestion. Fresh leaves crushed with salt are used in a cataplasm to “ripen” malignant tumors. Used to treat heart palpitations. Hot H2O Ext Oral Hot H2O Ext Oral Not Stated Human A dult Human Female Human A dult W 01316 Leaf Jamaica ZZ1020 Bark Jamaica Hot H2O Ext Oral Human A dult ZZ1020 Leaf Madagascar Leaf Malaysia Infusion Oral Decoction Oral Leaves External Not stated Human A dult Human A dult Human A dult Human A dult L15693 K26834 J13478 ZZ1093 Fruit Peru Bud Peru Leaf Peru Not stated Decoction Oral Decoction Oral Decoction Oral Cataplasm External Human A dult Human A dult Human A dult Human A dult Human A dult ZZ1093 L04137 ZZ1045 ZZ1093 ZZ1093 20 . asthma.

Used as a sedative and antispasmodic. Claimed to be a tranquillizer. Used as a sedative and antispasmodic. Crushed seeds and seed oil used as an insecticide. Decoction used to ease delivery. pediculosis. dysentery. Typ e Extract / Route Decoction Oral Maceration External Used For Human A dult Human A dult Ref # ZZ1027 ZZ1093 Bark Peru Root Peru Not stated South America Decoction Oral Hot H2O Ext Oral Not stated Human A dult Human A dult Human A dult ZZ1045 ZZ1045 ZZ1050 Leaf Surinam Leaf Togo Leaf Trinidad Leaf West Indies Infusion Oral Decoction Oral Hot H2O Ext Oral Hot H2O Ext Oral Hot H2O Ext Oral Hot H2O Ext Oral Fruit Oral Hot H2O Ext Oral Human A dult Human A dult Human A dult Human (pregnant) Human A dult Human Adult Human A dult Human A dult J14527 M23556 T05032 T00701 T00701 ZZ1021 ZZ1021 ZZ1021 Fruit Wes t Indies Bark West Indies 21 . and parasites. Used to treat diabetes. Used for chills. hypertension. asthma. flu. gallbladder attacks. Used to lower high blood pressure and as a galactagogue. kidneys. diarrhea and as a lactogogue. ringworm. hypertension. Used for hypertension and parasites. worms and diarrhea. Used for difficult childbirth. fever. Used to treat diabetes. Used for hypertension. diarrhea. for skin parasites and lice. dyspepsia. colds. sores and internal ulcers. insomnia. parasites. palpitations. Used for fevers. nervousness.Part / Location Seed Peru Documented Ethnom edical Use Used to kill parasites. Used for malaria.

00566% 00.0% 00. trans Annomutacin Annonacin Leaf Leaf Leaf Leaf Leaf Leaf Pericarp Seed Seed Seed Root Leaf 22 .0004% 00.00906% 00.0032% 01. cis Annomuricatin B Annomuricin A Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Taiwan Not stated Guyana Guyana Taiwan China Indonesia Colombia Indonesia Indonesia Indonesia Indonesia Indonesia Indonesia Colombia Brazil USA Guyana Guinea Indonesia Not stated Not stated 00.Presence of Compounds in Graviola (Annona muricata) Compound Annocatacin A Chemical Type Misc Lactone Plant Part Leaf Seed Leaf Seed Leaf Leaf Seed Seed Seed Seed Leaf P ericarp Plant Origin Taiwan Quantity Not stated Ref # AA1034 Annocatacin B Misc Lactone Taiwan Not stated AA1034 Annocatalin Annohexocin Annomonicin Annomontacin Annomontacin.02674% Not stated 00. cis: Annomuricin-D-one.0004% 00.06818% 00.000235 00.0003% 00.00035% 00.00603% Not stated 00.05411% AA1009 H17799 H07609 H07609 AA1009 H21843 H16272 L07801 H16272 H16273 H24563 H19306 H19306 H17568 L07801 K20560 K10338 H07236 H19768 H16272 Annomuricin B Annomuricin C Annomuricin E Annomuricin-D-one.0003% 00.00035% 00.0021% 00.

00142% 00. cis: Annonacin. iso: neo: Annonacin-A-one.4-trans Annonacin-10-one Annonacin-10-one. trans-2-4: 10(r): Annonacinone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Annonaine Annopentocin A Annopentocin B Annopentocin C Isoquinoline A lkaloid Misc Lactone Misc Lactone Misc Lactone 23 .Compound Annonacin A Chemical Type Misc Lactone Plant Part Pericarp Leaf Seed Seed Not stated Seed Seed Leaf Leaf Seed Seed Seed Seed Seed Seed Leaf Leaf Seed Seed Seed Seed Fruit Leaf Leaf Leaf Plant Origin Colombia Indonesia China China China Dominican Republic USA Indonesia Indonesia China China USA Dominican Republic USA China Indonesia Indonesia Guyana Guyana Brazil Guyana Surinam Indones ia (cult) Indones ia (cult) Indones ia (cult) Quantity 00. iso: 2-4-cis: Annonacin.00113% Not stated 00. cis: Annonacin-10-one.00521% Not stated 00. cis-2-4: 10(r): Annonacin-A-one.0021% Not stated 00.00017% 00.01811% 00.07% 00.00697% Not stated 00.2% 01. iso: 10-one. iso: Annonacin.000909% 00.00136% 00.0004% 00.00277% Not stated Not stated Not stated Not stated 00.0005% 00.00017% 00. iso: 2-4-trans: Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Annonacin.00035% Ref # L07801 H16274 H22999 H22999 H20484 H18307 K10338 H16274 H16274 AA1011 AA1011 K10338 H18307 K10338 H15501 H17568 H17568 H07609 H07609 K20560 H07236 J14527 H19306 H19306 H19306 Annonacin B M esitoate Annonacin. 2. iso: Annonacin-10-one.00109% 00.

(+): Coreximine.(+): Isoquinoline A lkaloid Cohibin A Misc Lactone Cohibin B Misc Lactone Cohibin C Cohibin D Corepoxylone Coreximine.0003% Ref # T02076 T04073 T04073 T02076 T04073 T04073 J10986 A04099 W 02289 J10986 A04095 T02076 T04073 T02076 T04073 T04073 H26434 H19768 H26434 H19768 H26434 H26434 H12235 T02076 T04073 T04073 H28460 Anomurine Isoquinoline A lkaloid Anonaine Anonol Isoquinoline A lkaloid Alkanol C5 or More Asimilobine Atherospermine Atherosperminine Isoquinoline A lkaloid Isoquinoline A lkaloid Isoquinoline A lkaloid Coclaurine.Compound Anomuricine Chemical Type Isoquinoline A lkaloid Plant Part Root Bark Leaf Root Bark Leaf Fruit Leaf Leaf Fruit Stembark Root Bark Root Bark Leaf Seed Root Seed Root Seed Seed Seed Root Bark Leaf Root Plant Origin Guyana Guyana Guyana Guyana Guyana Guyana Surinam Dominican Republic W est Indies Surinam Philippines Bark Bark Guyana Guyana Guyana Brazil Guinea Brazil Guinea Brazil Brazil Brazil Guyana Guyana Guyana Guinea Quantity Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated Not stated 00.00116% Not stated Not stated Not stated Not stated 00.00062% Not stated Not stated Not stated 00. (-): Misc Lactone Misc Lactone Misc Lactone Isoquinoline A lkaloid Isoquinoline A lkaloid Coronin Misc Lactone 24 .

4-cis Gigantetrocinone.01% Not stated 00. cis: Javoricin Misc Lactone Misc Lactone 25 . 2.00072% Ref # H07236 K20560 H28040 H07236 K20560 H14312 H28040 AA1009 H22999 H14312 H19768 H14312 H19768 A06190 K10338 H12985 H12985 AA1011 AA1011 H16273 H07609 K10338 H16272 H18307 K20560 H18307 H18307 Corossolone Misc Lactone Coross olone.00568% Not stated 00.00221% 00.00278% Not stated Not stated 00.4-trans Gigantetronenin Goniothalamicin Benzenoid Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Goniothalamicin.0005% 00.01660% 00.00042% Not stated Not stated 00.Compound Coross olin Chemical Type Misc Lactone Plant Part Seed Seed Seed Seed Seed Seed Seed Leaf Seed Seed Root Seed Root Leaf Seed Seed Seed Seed Seed Leaf Seed Seed Leaf Seed Seed Seed Seed Plant Origin Guyana Brazil Taiwan Guyana Brazil Brazil Taiwan Taiwan China Brazil Guinea Brazil Guinea Trinidad USA Dominican Republic Dominican Republic China China Indonesia Guyana USA Indonesia Dominican Republic Brazil Dominican Republic Dominican Republic Quantity 00.02% 00.00136% Not stated Not stated Not stated 00.00290% 01.00232% 01.00127% 00.00278% Not stated 00.00059% Not stated 00. cis Donhexocin Epomuricenin A Misc Lactone Misc Lactone Misc Lactone Epomuricenin B Misc Lactone Gentisic A cid Gigantetrocin Gigantetrocin A Gigantetrocin B Gigantetrocinone.00181% 00. 2.

00233% Not stated Not stated Not stated Not stated Not stated Not stated Not stated 00.00028% Not stated Not stated Not stated 00.00045% Not stated Not stated Ref # W 02289 A04099 A04099 W 02289 A04099 AA1017 H07609 H19211 H28040 H28040 H28040 H28040 H28040 H28040 H28040 H24563 AA1027 AA1027 AA1011 H12985 H16272 H28040 H12985 H16272 H28040 Lignoceric Acid Linoleic A cid Lipid Lipid Longifolicin Montanacin Montecristin Muracin A Muracin B Muracin C Muracin D Muracin E Muracin F Muracin G Muricapentocin Muricatalicin Muricatalin Muricatenol Muricatetrocin A Not stated Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Muricatetrocin B Misc Lactone 26 .Compound KCL Chemical Type Inorganic Plant Part Leaf Leaf Leaf Leaf Leaf Seed Seed Root Seed Seed Seed Seed Seed Seed Seed Leaf Leaf Leaf Seed Seed Leaf Seed Seed Leaf Seed Plant Origin W est Indies Dominican Republic Dominican Republic W est Indies Dominican Republic China Guyana Guinea Taiwan Taiwan Taiwan Taiwan Taiwan Taiwan Taiwan Indonesia China China China Dominican Republic Indonesia Taiwan Dominican Republic Indonesia Taiwan Quantity Not stated Not stated Not stated Not stated Not stated Not stated 00.02490% 00.00045% Not stated Not stated 00.

00311% 00.0093% Not stated Not stated Not stated Not stated 00.0004% Not stated Not stated Not stated Not stated H16274 H16273 AA1009 AA1009 A04104 A05062 A04104 A05062 H22688 H17719 H17719 H22688 H22999 H12242 H06211 H21114 H14312 H07236 AA1011 A04099 W 02289 AA1022 H21880 Muricinine Alkaloid-misc Bark Not stated Not stated Muricoreacin Murihexocin 3 Murihexocin A Murihexocin C Murihexol Murin A.Compound Muricatin D Muricatocin A Chemical Type Misc Lactone Misc Lactone Plant Part Seed Leaf Plant Origin China Indonesia Quantity 00.00038% Not stated Not stated 00.00060% 00. cis Not stated Misc Lactone .00930% 00.00035% Not stated 00. epoxy: Murisolin Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Leaf Leaf Leaf Leaf Seed Stembark Seed Seed Seed Seed Seed Leaf Leaf Not stated Root 27 Indonesia USA USA Indonesia China India French Guiana China Brazil Guyana China Dominican Republic W est Indies Italy Guinea 00.00216% N-fatty acyl tryptamines Oleic Acid Lipid Lipid Otivarin Panatellin.00015% 00.00045% Ref # H21114 H16274 Muricatocin B Muricatocin C Muricin H Muricin I Muricine Misc Lactone Misc Lactone Misc Lactone Misc Lactone Alkaloid-misc Leaf Leaf Seed Seed Bark Indonesia Indonesia Taiwan Taiwan Not stated 00.00085% 00.

00036% Not stated Not stated 00.0005% Not stated H14312 H12242 K20560 K20560 H07234 H21880 H17568 H21880 H21880 AA1009 Solamin. cis Xylomaticin Misc Lactone Isoquinoline A lkaloid Misc Lactone Misc Lactone Misc Lactone OTHER PHYTOCHEMICAL SCREENING: Alkaloids Absent Alkaloids Present Leaf + Stem Bark + Leaf + Seed Leaf Entire Plant T05306 L16047 A04099 T06830 Leucoanthocyanins Present Quinones Absent Saponins Absent Hydrocyanic Acid Absent Entire Entire Entire Entire Plant Plant Plant Plant T06830 T06830 T06830 T06830 28 . cis: Uv ariamicin IV.00043% 00.00083% 00.00116% 00.00285% Not stated Not stated 00.Compound Reticulatacin. cis: Reticuline Reticuline. n-para-coumaroyl: Uvariamicin I.00116% Ref # H21880 A04095 T02076 T04073 T04073 H26304 H21114 K20560 K20560 H25221 Robustocin Rolin B. (+) Chemical Type Misc Lactone Isoquinoline A lkaloid Isoquinoline A lkaloid Plant Part Root Stembark Root Bark Leaf Seed Seed Seed Seed Seed Plant Origin Guinea Philippines Guyana Guyana Guyana Brazil China Brazil Brazil Guinea Quantity 00.00083% Not stated Not stated Not stated Not stated 00.00216% Not stated 00. cis: Tyramine.00005% 00. epoxy: Rolliniastatin 1 Rolliniastatin 2 Sabadelin Misc Lactone Misc Lactone Misc Lactone Misc Lactone Misc Lactone Solamin Misc Lactone Seed Stembark Seed Root Seed Root Leaf Root Root Seed Brazil India Brazil Guinea French Guiana Guinea Indonesia Guinea Guinea Taiwan 00.

Active Inhibited the growth of Lewis lung carcinoma tumors by 57. vs.0 ml/animal 0.Documented Biological Activities for Extracts of Graviola (Annona muricata) IN VIVO RESEARCH Plant Part / Origin Leaf Gabon Leaf Gabon Activity Tested For Toxic Effect (general) Toxic Effect (general) Type Extract ETOH(95%) Ext ETOH(95%) Ext Test Model IP Mouse IP Mouse Dosage 100. strychnine-induced convulsions.1 ml/kg Not stated 1.9% without toxicity Uterus (unspec.0 ml/animal. Hind Quarter (isolated) vs.033 ml/liter 0.033 ml/liter 0. pentylenetetrazolinduced seizures.0 mg/kg 300. Reduction in explorative behavior and abdominal constrictions observed. Minimum toxic dose 1.05 Level. Results significant at P < 0.cond).cond). Uterus (unspec. metrazole-induced convulsions and vs. A04104 M29843 A03360 K29500 Leaf Nigeria Anticonvulsant Activity ETOH(70%) Ext IP Mouse Dose Variable Inactive T06510 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 29 .0 mg/kg Active Active Active Active Active Active Active Active A03360 A03360 Heart BP fell by more than 30%.033 ml/liter 100.0 mg/kg Results Inactive Active Notes / Organism Tested No toxicity noted. Ref # K29500 K29500 Leaf + Stem Jamaica Leaf Not stated Toxicity Assessment (quantitative) Cytotoxic / Antiproliferative Activity H2O Ext Fraction: Annonacin IP Mouse IP Mouse Various 10 mg/kg A03360 AA1032 Leaf + Stem Jamaica Leaf + Stem Jamaica Bark Not stated Leaf Cuba Leaf + Stem Jamaica Leaf Gabon Uterine Stimulant Effect Hypertensive Activity Cardiac Depressant Activity Hypotensive Activity Vasodilator Activity Anticonvulsant Activity ETOH(95%) Ext H2O Ext ETOH(95%) Ext H2O Ext H2O Ext H2O Ext ETOH(95%) Ext ETOH(95%) Ext Oral Rat Oral Rat IV Dog IV Dog Rabbit IV Rat IP Rat IP Mouse 0.1 ml/kg 0.

vs.0 mcg/ml Weak Activity Active Active Active J10986 Fruit Surinam Juice CHCL3 Ext 100.033 ml/liter 0. tail flick test.3 ml/liter 2.0 mcg/ml 100. Inhibited the binding of 3h-rauwolscine to serotonin receptors.Plant Part / Origin Leaf Brazil Leaf Brazil Leaf + Stem Jamaica Leaf + Stem Jamaica Leaf Cuba Activity Tested For Analgesic Activity Analgesic Activity Smooth Muscle Relaxant Activity Spasmogenic Activity Inotropic Effect Positive Type Extract ETOH-H2O (1:1) Ext ETOH-H2O (1:1) Ext ETOH(95%) Ext H2O Ext ETOH(95%) Ext H2O Ext Hot H2O Ext Test Model IG Mouse IG Mouse Rabbit Rabbit Guinea Pig Guinea Pig Guinea Pig Dosage 1.0 mcg/ml J10986 Seed Surinam MEOH Ext J10986 Stembark India Stembark India ETOH(100%)Ext ETOH(100%)Ext 100.2 ml/liter 0. Inhibited the binding of 3h. cold immobilization stress-induced increase in lipid peroxidation. Brain Brain J10426 Stembark India Stembark India 5-hydroxyindole-3-acetic Acid Inhibition Antiulcer Activity ETOH(100%)Ext ETOH(100%)Ext IG Rat GI Rat 100.0 gm/kg 3.032 ml/liter Results Inactive Inactive Active Active Active Active Inactive Notes / Organism Tested vs.033 ml/liter 0.rauwolscine to serotonin receptors.0 mg/kg Active Active L19052 L19052 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 30 . writhing test.0 mcg/ml 100. Inhibited the binding of 3h-rauwolscine to serotonin receptors. cold stress-induced ulcers.0 mg/kg Active Weak Activity L19052 J19242 Leaf Surinam Serotonin (5-ht) Receptor Binding Activity Serotonin (5-HT) Receptor Binding Activity Serotonin (5-HT) Receptor Binding Activity Dopamine Increase Norepinephrine Level Increase CHCL3 Ext Calf Hippocampus Calf Calf Calf Hippocampus IG Rat IG Rat 100. Brain Statistical data in report indicating significant results vs.0 gm/kg 1.0 mg/kg 100. Duodenum Ileum Atrium Ref # M18488 M18488 A03360 A03360 M29843 Stembark India Antioxidant Activity ETOH(95%)Ext IG Rat 100.0 mg/kg Active vs.0 mg/kg 100.

67 mcg/ml ED50<20.2.) CA-9KB.15 Ref # J13478 Leaf Borneo Leaf Costa Rica Leaf USA-FL Leaf Colombia Leaf Indonesia Leaf Indonesia Stem Costa Rica Leaf Taiwan Seed China ETOH(95%) Ext ETOH(95%) Ext ETOH(95%) Ext ETOH(100%) Ext ETOH(95%)Ext Not stated ETOH(95%)Ext ETOH(95%)Ext Fractions: Acetogenins Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture 20.0 mcg/ml ED50<20 mcg/ml ED50<20 mcg/ml IC50=2.05 level) CA-9KB CA-9KB Cells-MDBK CA-Mammary-MCF-7 CA-A498 CA-9KB Human hepatoma Hep G 2.9 mcg/ml IC50=0.0 mg/kg 100.0 mcg/ml Not stated Not stated Active Active Active Active Active Active Active Active Active K27823 X00001 X00001 L12082 H24563 H19306 X00001 AA1009 AA1017 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 31 . (Results significant at p < 0.0 mg/kg Results Active Active Notes / Organism Tested Brain Brain Ref # L19052 L19052 Documented Biological Activities for Extracts of Graviola (Annona muricata) IN VITRO RESEARCH Plant Part / Origin Leaf Malaysia Activity Tested For Epstein-barr Virus Early Antigen Induction Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Type Extract Ether Ext Test Model Cell Culture Dosage 1.15 Human hepatoma Hep G(2) and 2.Epstein-barr (Assay designed to test for tumor promoting activity.0 mcg/ml Results Inactive Notes / Organism Tested Virus .2.Plant Part / Origin Stembark India Stembark India Activity Tested For Monoamine Oxidase Activity Increase Serotonin (5-ht) Release Inhibition Type Extract ETOH(100%)Ext ETOH(100%)Ext Test Model IG Rat IG Rat Dosage 100.0 mcg/ml ED50=1.

The acetogenins were more potent than doxorubicin. 15. Six human tumor cell lines including prostate adenocarcinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines. enhanced caspase-3 activity. Pgp+) tumor cells. human breast adenocarcinoma MDA-MB231. liver. Annonacin activated p21 in a p53-independent manner and arrested T24 cells at the G1 phase.Plant Part / Origin Seed Korea Activity Tested For Cytotoxic Activity Type Extract Fractions: Acetogenins Test Model BST Dosage Not stated Results Active Notes / Organism Tested Six human tumor cell lines including prostate adenocarcinoma (PC-3) and pancreatic carcinoma (PACA-2) cell lines. and caused apoptotic cell death in T24 cells. Selective toxicity to a panel of human tumor cells. human breast carcinoma MCF-7. Human hepatoma cell lines Hep G2. It also induced Bax expression. including multidrug-resistant SW480 (P-glycoprotein+. breast. lung. Murine leukemia L1210. Ref # AA1020 Seed + Leaf Taiwan Seed France Cytotoxic Activity Cytotoxic Activity Fractions: Acetogenins Fractions: Acetogenins Cell Culture Not stated Not Stated Not stated Strong Activity Active AA1034 AA1031 Leaf USA Cytotoxic Activity Fractions: Muricoreacin Murihexocin C Cell Culture Not stated Active H22688 Leaf USA Cytotoxic Activity Fractions: Annonacin Cell Culture Not stated Strong Activity AA1033 Seed Not Stated Cytoxic Activity Fraction: Annonacin Cell Culture Not stated Active AA1036 Not Stated Cytotoxic Activity Fractions: Acetogeninis Cell Culture Not stated Active AA1035 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 32 . and ovarian tumor cell lines. Colon. 2. 2.

P03. M17/adr cancer cell lines. Colon. and ovarian tumor cell lines. L1210 leukemia cells (Predicts antitumor activity.5 mcg/ml Not stated Active Active Human hepatoma 2. HT-29 (colon adenocarcinoma). Demonstrated antitumor activity.Plant Part / Origin Stembark USA Activity Tested For Cytotoxic Activity Type Extract Fractions: Acetogenins Test Model Cell Culture Dosage Not stated Results Active Notes / Organism Tested Human tumor cell lines A549 (lung carcinoma).H125 cancer cell lines. breast. adriamycin resistant tumor cells. AA1021 Acetogenins France Cytotoxic Activity Fractions: Acetogenin analogs Fractions: Acetogenins CHC13 Ext Cell Culture Not stated Active AA1015 Acetogenins USA Cytostatic Activity Not stated Not stated Active AA1015 Seed China Antitumor Activity Cell Culture Not stated Active AA1011 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 33 . human H8. Human tumor cell lines. Neurospora crassa AA1030 AA1013 Acetogenins USA Cytotoxic Activity Cell Culture Not stated Active Murine P388 leukemia. Human tumor cell lines. liver. lung. U-937 Ref # AA1025 Not Stated Bark USA Leaf + Twig USA Bark Venezuela Pericarp Colombia Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Cytotoxic Activity Fractions: Acetogeninis Fraction: Gigantetronenin Not Stated Fraction: Xylomaticin Hexane Ext Ethyl acetate Ext MEOH Ext MTT H2O Ext ETOH Ext Ketonic Ext Fractions: Acetogenins Cell Culture Cell Culture Cell Culture Cell Culture Cell Culture Not stated Not stated Not stated Not stated Not stated Active Active Active Active Active AA1037 AA1026 AA1023 AA1024 AA1029 Leaf Colombia Leaf Cuba Cytotoxic Activity Cytostatic Activity Cell Culture Agar plate CC50=49. Human solid tumor cell lines. MCF7 (breast carcinoma).) Adriamycin resistant human mammary adenocarcinoma (MCF-7/Adr) cells. nonadriamycin resistant tumor cells.

HSV-2 Virus.50 mcg/ml 1.Herpes simplex 1 Neurospora crassa Ref # AA1021 H16272 L09586 Stem Puerto Rico Colombia Stembark India Leaf Cuba Antiviral Activity Antiviral Activity Antiviral Activity Antifungal Activity H2O Soluble Fraction MTT ETOH(95%) Ext Acetone Ext ETOH(95%) Ext H2O Ext Hot H2O Ext Agar Plate Cell Culture Cell Culture Agar Plate Not stated CC50 & EC50 = 0.) K23019 Leaf Dominican Republic Antioxidant Effect Decoction Cell Culture 1.HIV Virus .17 mcg/ml IC50<2. Results indicate it has an antiproliferative effect rather than a cytotoxic effect on HIV-infected cells.0 mg/plate Weak Activity Hepatocytes (Measured by leakage of LDH and ASAT. Reduced the leakage of ASAT) Hepatocytes (Monitored by production of malonaldehyde.0 mg/plate Inactive K23019 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 34 . Virus . vs.Plant Part / Origin Acetogenins USA Leaf Indonesia Stem Puerto Rico Activity Tested For Antiproliferative Activity Anticrustacean Activity Cytotoxic / Anti-HIV Activity Type Extract Fractions: Acetogenins ETOH(95%) Ext H2O Soluble Fraction Test Model Cell Culture Artemia salina larvae Cell Culture Dosage Not stated LC50=0. Assay system is intended to predict for antitumor activity. CEM-SS Cells.0 mcg/ml Results Inactive Active Active Notes / Organism Tested Non-cancerous GI epithelial cell line (I18).0 mg/ml 50% Inactive Active Active Inactive L09586 AA1030 J19169 T08589 Leaf Guatemala Antifungal Activity Broth Culture 1.0 ml Inactive Epidermophyton floccosum Microsporum canis Microsporum gypseum Trichophyton mentagrophytes Trichophyton rubrum Neurospora crassa M27151 Stem Cuba Antifungal Activity Acetone Ext ETOH(95%) Ext H2O Ext Decoction Agar Plate 50% Inactive T08589 Leaf Dominican Republic Antihepatotoxic Activity Cell Culture 1.

dessetae A.0 mg/liter Results Inactive Notes / Organism Tested Measured by decoloration of diphenylpicryl hydroxyl radical solution.0 mcg/ml Weak Activity Inactive Active Active K16971 K16971 M23556 K27823 Leaf Cuba Antibacterial Activity H2O Ext Agar Plate Not stated Active K09159 Leaf Cuba Antibacterial Activity Acetone Ext Agar Plate Not stated Active K09159 Stembark Papua-New Guinea Antibacterial Activity MEOH Ext Agar Plate 1 mg/disc Active L03211 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 35 .9 mcg/ml 20. (Results significant at P < 0. panamensis L. salina Plasmodium falciparum W-2 Plasmodium falciparum D-6 Plasmodium falciparum Plasmodium falciparum D-6 & W-2.0 mcg/ml IC50 > 63 mcg/ml IC50=39.Plant Part / Origin Leaf Dominican Republic Stembark France Pericarp Colombia Activity Tested For Radical Scavenging Effect Type Extract Decoction Test Model Not stated Dosage 250. Leishmania trypansoma Leishmania braziliensis L. histolytica N. promastigotes E.01 Level) Escherichia coli Pseudomonas aeruginosa Shigella flexneri Escherichia coli Pseudomonas aeruginosa Salmonella B Salmonella newport Salmonella typhosa Serratia marcescens Shigella flexneri Shigella flexneri 3a Staphylococcus albus Staphylococcus aureus Staphylococcus aureus Escherichia coli Ref # K23019 Antiparasitic Activity Antiparasitic Activity MEOH Ext Hexane Ext Ethyl Acetate Ext MEOH Ext MEOH Ext In vitro In vitro Not stated Not stated Active Active AA1032 AA1029 Seed France Antiparasitic Activity In vitro Not stated Active M28527 Leaf Puerto Rico Leaf Puerto Rico Leaf Togo Leaf Borneo Antimalarial Activity Antimalarial Activity Antimalarial Activity Antimalarial Activity ETOH(95%) Ext ETOH(95%) Ext ETOH(95%) Ext ETOH(95%) Ext RBC RBC RBC RBC IC50=20. brasiliensis M.

0 mg/disc Not stated 1.0 mg/disc Not stated L03211 K09159 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 36 .Plant Part / Origin Stem Cuba Activity Tested For Antibacterial Activity Type Extract Acetone Ext Test Model Agar Plate Dosage Not stated Results Active Notes / Organism Tested Escherichia coli Salmonella B Salmonella newport Salmonella typhosa Shigella flexneri Shigella flexneri 3A Escherichia coli Pseudomonas aeruginosa Salmonella newport Salmonella typhosa Salmonella B Shigella flexneri Bacillus subtilis Staphylococcus albus Klebsiella pneumoniae Pseudomonas aeruginosa Staphylococcus aureus Sarcina lutea Escherichia coli Staphylococcus aureus Escherichia coli Escherichia coli Pseudomonas aeruginosa Salmonella B Salmonella newport Salmonella typhosa Sarcina lutea Serratia marcescens Shigella flexneri Shigella flexneri 3a Staphylococcus albus Staphylococcus aureus Ref # K09159 Stem Cuba Antibacterial Activity H2O Ext Agar Plate Not stated Active K09159 Stembark Papua-New Guinea Antibacterial Activity ETOH(95%) Ext Agar Plate 2-3 mcg/plate Active Active Inactive Inactive Weak Activity Inactive Weak Activity Inactive Inactive K15021 Leaf Papua-New Guinea Leaf Cuba Stembark Papua-New Guinea Leaf Papua-New Guinea Leaf Cuba Antibacterial Activity Antibacterial Activity Antibacterial Activity ETOAC Ext MEOH Ext Acetone Ext ETOAC Ext Agar Plate Agar Plate Agar Plate 1.0 mg/disc L03211 K09159 L03211 Antibacterial Activity Antibacterial Activity ETOAC Ext ETOH(95%) Ext Agar Plate Agar Plate 1.

Plant Part / Origin Leaf Trinidad Activity Tested For Antibacterial Activity Type Extract ETOAC Ext Test Model Agar Plate Dosage 1000 mcg/ml Results Inactive Notes / Organism Tested Escherichia coli Pseudomonas aeruginosa Salmonella typhimurium Staphylococcus aureus Staphylococcus epidermidis Streptococcus faecalis Pseudomonas aeruginosa Sarcina lutea Serratia marcescens Staphylococcus albus Staphylococcus aureus Salmonella B Salmonella newport Salmonella typhosa Sarcina lutea Serratia marcescens Shigella flexneri 3a Staphylococcus albus Staphylococcus aureus Staphylococcus aureus Streptococcus faecalis Escherichia coli Salmonella typhimurium Staphylococcus epidermidis Sarcina lutea Serratia marcescens Shigella flexneri 3A Staphylococcus albus Staphylococcus aureus Escherichia coli Pseudomonas aeruginosa Salmonella B Salmonella newport Salmonella typhosa Sarcina lutea Serratia marcescens Shigella flexneri Staphylococcus albus Staphylococcus aureus IM = Intramuscular Ref # L13922 Stem Cuba Antibacterial Activity Acetone Ext Agar Plate Not stated Inactive K09159 Leaf Cuba Antibacterial Activity H2O Ext Agar Plate Not stated Inactive K09159 Leaf Trinidad Antibacterial Activity Pet Ether Ext Agar Plate 1000 mcg/ml Equiv. Inactive Inactive Inactive Inactive L13922 Stem Cuba Antibacterial Activity H2O Ext Agar Plate Not stated K09159 Stem Cuba Antibacterial Activity ETOH(95%) Ext Agar Plate Not stated Inactive K09159 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously 37 . Equiv.

26 ppm LD90 < 20 ppm LD90 < 20 ppm LD50 = 11. decemlineata M.0 ppm LD50 = 0.0% Not stated Not stated Not stated 18 mcg/ml Results Inactive Inactive Active Active Active Active Inactive Weak Activity Active Active Active Equiv. Ref # L12432 L15585 L15585 L15585 AA1028 AA1012 M19731 W00220 AA1018 AA1019 AA1018 AA1010 GI = Gastric Intubation IG = Intragastric IP = Intraperitoneally IV = Intravenously SC = Subcutaneously IM = Intramuscular 38 . Notes / Organism Tested Mycobacterium tuberculosis Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Biomphalaria glabrata Culex quinquefasciatus Macrosiphoniella sanborni L. decemlineata Dopaminergic nerve cells and GABAergic nerve cells.Plant Part / Origin Leaf Puerto Rico Stem Brazil Dried Stembark Brazil Leaf Brazil Leaf Brazil Brazil Leaf + Stem India Leaf Not Stated Spain USA Spain Root bark Taiwan Activity Tested For Antimycobacterial Activity Molluscicidal Activity Molluscicidal Activity Molluscicidal Activity Molluscicidal Activity Molluscicidal Activity Larvicidal Activity Insecticide Activity Insecticide Activity Insecticide Activity Antifeedant Activity Dopaminergic modulation Type Extract ETOH(95%) Ext ETOH(100%) Ext ETOH(100%) Ext ETOH(100%) Ext Not stated Not stated H2O Ext ETOH(95%) Ext Fraction: Squamocin Fraction: Acetogenins Fraction: Annonacin Alkaloid Ext Test Model Agar Plate Not stated Adult snail Egg masses Adult Snail Egg Masses Adult Snail Egg Masses Adult Snail Egg Masses Not stated Not stated Agar plate In vitro Agar plate Cell culture Dosage Not stated 100.59 ppm LD50 = 20. persicae Blattella germanica (L.97 ppm LD50 = 1.86 ppm LD50 = 49.03 gm/ml 5.62 ppm 0.) L.0 ppm LD50 = 1.

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