graviola, annona, muricata, tree, guanabana, paw-paw, paw, soursop, HSI, natural, remedies, herbs, herbal, treatment, alternative, health, formulas Graviola Capsules

Annona muricata

This product is no longer sold by Raintree Nutrition, Inc. See the main product page for more information why. Try doing a google search for products available from other suppliers or see the rainforest products page to find other companies selling rainforest herbal supplements or rainforest plants if you want to make this rainforest formula yourself.

Some of the active ingredients documented, researched, and verified in graviola are a group of Annonaceous acetogenins which are only found in the Annonaceae family to which graviola belongs. These phytochemicals are being researched and patented around the world for their active biological actions and uses against cancer.* For more complete information on this powerful plant of the rainforest, please see the plant database file on graviola. Check out the new Discussion Forums to see if anyone is talking about how they are using this natural rainforest remedy. More information on graviola can be found the in the new Anti-Cancerous Guide

Graviola was featured in three articles by The Health Sciences Institute which are accessible here:

  • HSI Article 1

  • HSI Article 2

  • HSI Article 3

    Traditional Uses:* for cancer (all types); as a broad-spectrum internal and external antimicrobial to treat bacterial and fungal infections; for internal parasites and worms; for high blood pressure; for depression, stress, and nervous disorders

    Suggested Use: Take 2 grams three times daily, or as directed by a healthcare professional.

    Contraindications:
    • Not to be used during pregnancy or breast-feeding.
    • Graviola has demonstrated hypotensive, vasodilator, and cardiodepressant activities in animal studies (not confirmed in humans). People with low blood pressure should monitor their blood pressure accordingly.
    • Graviola has recently been documented to lower blood sugar in animal studies (not confirmed in humans). People with hypoglycemia and diabetes should monitor their blood sugar levels accordingly.
    Drug Interactions: None have been reported; however, based on animal studies, graviola may enhance the effect of high blood pressure drugs and diabetes drugs.

    Other Practitioner Observations:
    • Graviola has demonstrated in vitro antimicrobial properties. Chronic, long-term use of this plant might lead to some die-off of friendly bacteria in the digestive tract. Supplementing the diet with probiotics and digestive enzymes may be helpful to counteract this possible effect.
    • Graviola has demonstrated emetic properties in one animal study with pigs. Large single dosages may cause nausea or vomiting. Reduce the usage accordingly or take with a meal if nausea occurs.
    • Drinking plenty of water (at least 8 glasses a day) is helpful to reduce Herxheimer reactions and flush dead and dying cells from the body.
    • One of three documented mechanisms of action of graviola is by decreasing energy to abnormal cells (called an ATP-inhibitor). Taking supplements that increase cellular energy (like CoQ10) will counteract or disable this one mechanism of action of graviola (however, the other two mechanisms of action will be unaffected).




    Third-Party Published Research*

    All available third-party research on graviola can be found at PubMed/Medline. A partial listing of the published research on graviola is shown below:

    Anticancerous & Antitumor Actions:
    To date, over 80 Annonaceous acetogenins have been recorded in graviola which have shown in laboratory studies to be selectively cytotoxic to cancer cells without toxicity to healthy cells. Many of the acetogenins have demonstrated selective cytotoxicity to tumor cells with as little as 1 part per million. 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; human breast solid tumor lines; prostate adenocarcinoma; pancreatic carcinoma cell lines; colon adenocarcinoma cell lines; liver cancer cell lines; human lymphoma cell lines; skin cancer cell lines, and multi-drug resistant human breast adenocarcinoma. 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 promising anti-cancer agent and worthy of further animal studies and, we would hope, clinical trials."
    Researchers have reported several mechanisms of actions including inhibition of NADH oxidase in the plasma membranes of cancer cells (an enzyme only transiently expressed in normal healthy cells). Acetogenins also inhibit complex I (NADH/ubiquinone oxidoreductase) in mitochondrial electron transport systems, inhibiting oxidative phosphorylation and resulting in lower ATP levels. In addition, increased expression of a plasma membrane pump, P-glycoprotein, is a contributor to multidrug resistance. The pump activity in these multi-drug resistant cells requires large amounts of ATP. The acetogenins were found, through depletion of ATP, to reduce the activity or shut down the P-glycoprotein pump. Finally, acetogenins in graviola have shown to directly induce apoptosis to cancer cells. Cells at the S phase of their cell cycle were shown to be more vulnerable to the main graviola acetogenin, annonacin. Annonacin was able to arrest the cell cycle in the G1 phase, and inhibit the S phase progression. In addition, it was reported that p53 and p21 cell cycle checkpoint proteins, were enhanced by annonacin.

    Torres, M., et al. "Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism." Cancer Lett. 2012 Oct 1;323(1):29-40.
    de Pedro N, et al. "Analysis of cytotoxic activity at short incubation times reveals profound differences among Annonaceus acetogenins, inhibitors of mitochondrial Complex I." J Bioenerg Biomembr. 2012 Nov 21. [Epub ahead of print]
    de Pedro N, et al. "Mitochondrial complex I inhibitors, acetogenins, induce HepG2 cell death through the induction of the complete apoptotic mitochondrial pathway." J Bioenerg Biomembr. 2012 Nov 21. [Epub ahead of print]
    Hamizah, S., et al. "Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice." Asian Pac J Cancer Prev. 2012;13(6):2533-9.
    Chen, Y., et al. "Anti-tumor activity of Annona squamosa seeds extract containing annonaceous acetogenin compounds." J Ethnopharmacol. 2012 Jul 13;142(2):462-6.
    Chen, Y., et al. "Antitumor activity of annonaceous acetogenins in HepS and S180 xenografts bearing mice." Bioorg Med Chem Lett. 2012 Apr 15;22(8):2717-9.
    George, V., et al. "Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines." Asian Pac J Cancer Prev. 2012;13(2):699-704.
    Gomes de Melo, J., et al. "Antiproliferative activity, antioxidant capacity and tannin content in plants of semi-arid northeastern Brazil." Molecules. 2010 Nov 24;15(12):8534-42.
    Ko, Y., et al. "Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-?-related pathways in MCF-7 cells." J Ethnopharmacol. 2011 Oct 11;137(3):1283-90.
    Tantithanaporn, S., et al. "Cytotoxic activity of acetogenins and styryl lactones isolated from Goniothalamus undulatus Ridl. root extracts against a lung cancer cell line (COR-L23)." Phytomedicine. 2011 Apr 15;18(6):486-90.
    Coothankandaswamy, V., et al. "The alternative medicine pawpaw and its acetogenin constituents suppress tumor angiogenesis via the HIF-1/VEGF pathway." J Nat Prod. 2010 May 28;73(5):956-61.
    Yang, h., et al. "Structure-activity relationships of diverse annonaceous acetogenins against human tumor cells." Bioorg Med Chem Lett. 2009 Apr 15;19(8):2199-202.
    Kojima, N. “Systematic synthesis of antitumor Annonaceous acetogenins” Yakugaku Zasshi. 2004; 124(10):673-81
    Tormo, J. R., et al. “In vitro antitumor structure-activity relationships of threo/trans/threo mono-tetrahydro-furanic acetogenins: Correlations with their inhibition of mitochondrial complex I.” Oncol. Res. 2003; 14(3): 147-54.
    Yuan, S. S., et al. “Annonacin, a mono-tetrahydrofuran acetogenin, arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway.” Life Sci. 2003 May: 72(25): 2853-61.
    Liaw, C. C., et al. “New cytotoxic monotetrahydrofuran Annonaceous acetogenins from Annona muricata.J. Nat. Prod. 2002; 65(4): 470-75
    Gonzalez-Coloma, A., et al. “Selective action of acetogenin mitochondrial complex I inhibitors.” Z. Naturforsch. 2002; 57(11-12): 1028-34.
    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 plant extracts.” Mem. Inst. Oswaldo Cruz. 1999; 94(4): 531-35.
    Kim, G. S., et al. “Muricoreacin and murihexocin C, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricata.Phytochemistry. 1998; 49(2): 565-71.
    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.
    Nicolas, H., et al. “Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells.” J. Med. Chem. 1997; 40(13): 2102-6.
    Zeng, L., et al. “Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata.J. Nat. Prod. 1996; 59(11): 1035-42.
    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.
    Oberlies, N. H., et al. “Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay.” Cancer Lett. 1995; 96(1): 55-62.
    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): 909-5.
    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.
    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.

    Antimicrobial Actions:
    Feng, L., et al. "Specific inhibitions of annonaceous acetogenins on class II 3-hydroxy-3-methylglutaryl coenzyme A reductase from Streptococcus pneumoniae." Bioorg Med Chem. 2011 Jun 1;19(11):3512-9.
    Viera, G., et al. "Antibacterial effect (in vitro) of Moringa oleifera and Annona muricata against Gram positive and Gram negative bacteria." Rev Inst Med Trop Sao Paulo. 2010 May-Jun;52(3):129-32.
    Takahashi, J.A., et al. “Antibacterial activity of eight Brazilian Annonaceae plants.” Nat. Prod. Res. 2006;20(1):21-6.
    Betancur-Galvis, L., et al. “Antitumor and antiviral activity of Colombian medicinal plant extracts.” Mem. Inst. Oswaldo Cruz 1999; 94(4): 531-35.
    Antoun, M. D., et al. "Evaluation of the flora of Puerto Rico for in vitro cytotoxic and anti-HIV activities." Pharmaceutical Biol. 1999; 37(4): 277-280.
    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.
    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.
    Misas, C. A. J., et al. “Contribution to the biological evaluation of Cuban plants. IV.” Rev. Cubana Med. Trop. 1979; 31(1): 29–35.

    Antidepressant & Antistress Actions:
    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.
    Hasrat, J. A., et al. “Screening of medicinal plants from Suriname for 5-HT 1A ligands: Bioactive isoquinoline alkaloids from the fruit of Annona muricata.” Phytomedicine. 1997; 4(20: 133-140.
    Padma, P., et al. “Effect of alcohol extract of Annona muricata on cold immobilization stress induced tissue lipid peroxidation.” Phytother. Res. 1997; 11(4): 326-327.
    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.

    Antiparasitic, Antimalarial, & Insecticidal Actions:
    Grzybowski, A., et al. "Synergistic larvicidal effect and morphological alterations induced by ethanolic extracts of Annona muricata and Piper nigrum against the dengue fever vector Aedes aegypti." Pest Manag Sci. 2012 Sep 19. doi: 10.1002/ps.3409. [Epub ahead of print]
    Vila-Nova N., et al. "Leishmanicidal activity and cytotoxicity of compounds from two Annonacea species cultivated in Northeastern Brazil." Rev Soc Bras Med Trop. 2011 Oct;44(5):567-71.
    Broglio-Micheletti S., et al. "[Plant extracts in control of Rhipicephalus (Boophilus) microplus (Canestrini, 1887) (Acari: Ixodidae) in laboratory]." Rev Bras Parasitol Vet. 2009 Oct-Dec;18(4):44-8.
    Osorio, E., et al. "Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae." J Ethnopharmacol. 2007 May 22;111(3):630-5.
    Luna, J. S., et al. “Acetogenins in Annona muricata L. (Annonaceae) leaves are potent molluscicides.” Nat. Prod. Res. 2006; 20(3): 253-7.
    Jaramillo, M. C., et al. “Cytotoxicity and antileishmanial activity of Annona muricata pericarp.” Fitoterapia. 2000; 71(2): 183–6.
    Alali, F. Q., et al. “Annonaceous acetogenins as natural pesticides; potent toxicity against insecticide-susceptible and resistant German cockroaches (Dictyoptera: Blattellidae).” J. Econ. Entomol. 1998; 91(3): 641-9.
    Antoun, M. D., et al. "Screening of the flora of Puerto Rico for potential antimalarial bioactives.” Int. J. Pharmacog. 1993; 31(4): 255–58.
    Heinrich, M., et al. “Parasitological and microbiological evaluation of Mixe Indian medicinal plants (Mexico).” J. Ethnopharmacol. 1992; 36(1): 81–5.
    Bories, C., et al. “Antiparasitic activity of Annona muricata and Annona cherimolia seeds.” Planta Med. 1991; 57(5): 434–36.
    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.

    Anti-Diabetes Action:
    Adeyemi, D., et al. "Histomorphological and morphometric studies of the pancreatic islet cells of diabetic rats treated with extracts of Annona muricata." Folia Morphol (Warsz). 2010 May;69(2):92-100.
    Adeyemi, D., et al. "Anti hyperglycemic activities of Annona muricata (Linn)" Afr J Tradit Complement Altern Med. 2008 Oct 25;6(1):62-9.
    Adewole, S., et al. "Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats." Afr J Tradit Complement Altern Med. 2008 Oct 25;6(1):30-41.

    Anticonvulsant, Antispasmodic, & Smooth Muscle Relaxant Actions:
    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.
    Feng, P. C., et al. “Pharmacological screening of some West Indian medicinal plants.” J. Pharm. Pharmacol. 1962; 14: 556–61.

    Hypotensive & Cardiodepressant Actions
    Nwokocha, C., et al. "Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague-Dawley rats." Pharm Biol. 2012 Nov;50(11):1436-41.
    Carbajal, D., et al. “Pharmacological screening of plant decoctions commonly used in Cuban folk medicine.” J. Ethnopharmacol. 1991; 33(1/2): 21–4.
    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.

    Pain-Relieving & Anti-inflammatory Actions:
    de Sousa, O., et al. "Antinociceptive and Anti-Inflammatory Activities of the Ethanol Extract of Annona muricata L. Leaves in Animal Models." Int J Mol Sci. 2010 May 6;11(5):2067-78

    Antioxidant Actions:
    Nawwar, M., et al. "A flavonol triglycoside and investigation of the antioxidant and cell stimulating activities of Annona muricata Linn." Arch Pharm Res. 2012 May;35(5):761-7.
    Adewole, S., et al. "Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats." Afr J Tradit Complement Altern Med. 2008 Oct 25;6(1):30-41.
    Baskar, R., et al. "In vitro antioxidant studies in leaves of Annona species." Indian J Exp Biol. 2007 May;45(5):480-5.



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