Health Care Professional Information

Scientific Name
Annona muricata
Common Name

Guanabana, soursop, custard apple, brazilian paw paw

Clinical Summary

Graviola, a tree prevalent in the rain forests of Africa, South America, and Southeast Asia, has been used in traditional medicine in many countries.

Extracts of graviola show antiviral (1) , antiparasitic, antirheumatic, astringent, emetic (2), cytotoxic (3) (4) , antinociceptive, anti-inflammatory (5), antiplatelet (6), antidiabetic (7), antihyperglycemic (8), and anticancer effects (9) (10) (11) (12) in vitro and in vivo. However, human data are lacking.

Alkaloids extracted from graviola may cause neuronal dysfunction and degeneration leading to symptoms of Parkinson's disease (13) (14). Graviola may decrease the uptake of radiopharmaceuticals used in nuclear imaging (15).

Purported Uses
Constituents
  • Acetogenins: annosquamin B, bullatacin, annosquatin B, annonacin, annonacin A and annomuricin A muricins J, K, and L
  • Alkaloids
  • Quinolines and isoquinolines
  • Annopentocins
  • Coreximine and reticuline
  • Volatile oils: α-pinene, β-pinene, ρ-mentha-2,4(8)-diene ,β-elemene, germacrene D
  • Flavonol triglycoside: quercetin 3-O-rhamnosylsophoroside
  • Phenolics
    (3) (13) (14) (16) (17) (18) (19) (20)
Mechanism of Action

Annonaceous acetogenins, phytochemicals isolated from the leaves, bark, and twigs of graviola, are thought to be the active ingredients of graviola. The ethanolic extract of Annona muricata shows in vitro antiviral activity against the Herpes simplex virus (1), and antimicrobial activity against Leishmania (3). Graviola extracts were shown to be lethal to the fresh-water mollusk Biomphalaria glabrata, which acts as a host for the parasitic worm, Schistosoma mansoni (2).

Alkaloids from graviola are detrimental to the survival of dopaminergic nerve cells in vitro. This may result in neuronal dysfunction and degeneration. Graviola-induced cell death was inhibited by glucose supplementation suggesting that cell death may have been caused by energy depletion (13). Graviola has also been shown to stimulate serotonin receptors (16). An ethanolic extract produced cell-stimulating behaviors either by increased mitochondrial turnover indicating stimulation in protein production or by preparation to leave the G1 phase, perhaps due to promitotic stimulus present within the extract which acts like a growth factor (20).

Graviola extracts were effective against the growth of adriamycin-resistant human mammary adenocarcinoma (MCF-7/Adr) by blocking access of cancer cells to ATP and by inhibiting the actions of plasma membrane glycoprotein (9). They also inhibited expression of HIF-1α, NF-κB, glucose transporters, and glycolytic enzymes resulting in decreased glucose uptake and ATP production in pancreatic cancer cells (10), and downregulated EGFR expression in breast cancer cells (11). Phenolic compounds in graviola also demonstrate free-radical scavenging potential against human breast carcinoma cells (21). Extracts of acetogenin muricins J, K, and L have antiproliferative effects against human prostate cancer cells, with the effect of muricin K being strongest (19).

In animal models, the antidiabetic effects of graviola are due to its antioxidant, hypolipidemic and protective effects in pancreatic β-cells, which improves glucose metabolism (7). In rodent models of hepatic cancer, although constituents of graviola led to reduced tumor growth, the acetogenin bullatacin caused liver and kidney toxicity via increasing calcium concentration, ROS production, and Bax expression and Bax/Bcl-2 ratio with repeated treatment (17).

Warnings

Repeated use may increase liver and kidney toxicity (17).

Contraindications

Patients with hypertension or hyperglycemia (8) (22)
Patients with liver or kidney disease (17)

Adverse Reactions

Movement disorders and myeloneuropathy with symptoms mimicking Parkinson's disease (13) (14)

Herb-Drug Interactions

Antidiabetics: Graviola may have additive effects resulting in hypoglycemic symptoms (8).
Antihypertensives: Graviola may have additive effects resulting in hypotension (22).

Herb Lab Interactions

Nuclear imaging (radiopharmaceutical biodistribution): Graviola significantly decreased uptake of radioactivity per gram of tissue in bladder, kidney, and blood in animal models (15).
Blood glucose test: Graviola may reduce blood glucose levels (8).
Blood pressure readings: Graviola may reduce blood pressure readings (22).

Dosage (Inside MSKCC Only)
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References
  1. Padma P, Pramod NP, Thyagarajan SP, et al. Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus. J Ethnopharmacol. May 1998;61(1):81-83. doi:
  2. dos Santos AF, Sant'Ana AE. Molluscicidal properties of some species of Annona. Phytomedicine. Mar 2001;8(2):115-120. doi: 10.1078/0944-7113-00008
  3. Jaramillo MC, Arango GJ, Gonzalez MC, et al. Cytotoxicity and antileishmanial activity of Annona muricata pericarp. Fitoterapia. Apr 2000;71(2):183-186. doi:
  4. Liaw CC, Chang FR, Lin CY, et al. New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod. Apr 2002;65(4):470-475. doi:
  5. de Sousa OV, Vieira GD, de Jesus RGdPJ, et al. Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. Int J Mol Sci. 2010;11(5):2067-2078. doi: 10.3390/ijms11052067
  6. Awodele O, Ishola IO, Ikumawoyi VO, et al. Toxicological evaluation of the lyophilized fruit juice extract of Annona muricata Linn. (Annonaceae) in rodents. J Basic Clin Physiol Pharmacol. Dec 18 2013:1-11. doi: 10.1515/jbcpp-2013-0085
  7. Florence NT, Benoit MZ, Jonas K, et al. Antidiabetic and antioxidant effects of Annona muricata (Annonaceae), aqueous extract on streptozotocin-induced diabetic rats. J Ethnopharmacol. Feb 3 2014;151(2):784-790. doi: 10.1016/j.jep.2013.09.021
  8. Adeyemi DO, Komolafe OA, Adewole OS, et al. Anti hyperglycemic activities of Annona muricata (Linn). Afr J Tradit Complement Altern Med. 2008;6(1):62-69. doi:
  9. Oberlies NH, Chang CJ, McLaughlin JL. Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells. J Med Chem. Jun 20 1997;40(13):2102-2106. doi: 10.1021/jm9700169
  10. Torres MP, Rachagani S, Purohit V, 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. Oct 1 2012;323(1):29-40. doi: 10.1016/j.canlet.2012.03.031
  11. Dai Y, Hogan S, Schmelz EM, et al. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Nutr Cancer. 2011;63(5):795-801. doi: 10.1080/01635581.2011.563027
  12. Hamizah S, Roslida AH, Fezah O, et al. Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice. Asian Pac J Cancer Prev. 2012;13(6):2533-2539. doi:
  13. Lannuzel A, Michel PP, Caparros-Lefebvre D, et al. Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe. Mov Disord. Jan 2002;17(1):84-90. doi:
  14. Lannuzel A, Hoglinger GU, Champy P, et al. Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae? J Neural Transm Suppl. 2006(70):153-157. doi:
  15. Holanda CM, Barbosa DA, Demeda VF, et al. Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats. Acta Cir Bras. Mar 2014;29(3):145-150. doi: 10.1590/s0102-86502014000300001
  16. Roman G. Tropical myeloneuropathies revisited. Curr Opin Neurol. Oct 1998;11(5):539-544. doi:
  17. Chen Y, Chen JW, Zhai JH, et al. Antitumor activity and toxicity relationship of annonaceous acetogenins. Food Chem Toxicol. Aug 2013;58:394-400. doi: 10.1016/j.fct.2013.05.028
  18. Thang TD, Dai DN, Hoi TM, et al. Study on the volatile oil contents of Annona glabra L., Annona squamosa L., Annona muricata L. and Annona reticulata L., from Vietnam. Nat Prod Res. 2013;27(13):1232-1236. doi: 10.1080/14786419.2012.724413
  19. Sun S, Liu J, Kadouh H, et al. Three new anti-proliferative Annonaceous acetogenins with mono-tetrahydrofuran ring from graviola fruit (Annona muricata). Bioorg Med Chem Lett. Jun 15 2014;24(12):2773-2776. doi: 10.1016/j.bmcl.2014.03.099
  20. Nawwar M, Ayoub N, Hussein S, et al. A flavonol triglycoside and investigation of the antioxidant and cell stimulating activities of Annona muricata Linn. Arch Pharm Res. May 2012;35(5):761-767. doi: 10.1007/s12272-012-0501-4
  21. George VC, Kumar DR, Rajkumar 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. doi:
  22. Nwokocha CR, Owu DU, Gordon A, et al. Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague-Dawley rats. Pharm Biol. Nov 2012;50(11):1436-1441. doi: 10.3109/13880209.2012.684690

Consumer Information

How It Works

Bottom Line: Graviola showed anticancer effects in lab studies. Human data are lacking.
Graviola contains chemicals called acetogenins, which are thought to be the active ingredient. Extracts of graviola have been shown to be effective against a number of viruses, bacteria, and parasites in test tubes. Laboratory studies have also shown graviola to be effective against some types of cancer cells. However, substances derived from graviola can damage nerve cells and cause neurological side effects similar to Parkinson's disease. Graviola may also affect nuclear imaging because it has been shown to decrease the uptake of radiopharmaceuticals used in these procedures.

Purported Uses
  • To treat cancer
    Graviola has been shown effective against cancer cells in lab studies. Human studies have not been conducted.
  • To treat herpes
    Graviola is effective against the herpes virus in laboratory experiments. Human studies are needed.
  • To fight infections
    Lab studies indicate that graviola may prevent certain infections. Human data are lacking.
Patient Warnings

Repeated use may increase liver and kidney toxicity.

Do Not Take If

You are taking blood pressure medications: Graviola may  increase their effects.
You are taking diabetic medications: Graviola may increase their effects.
You have liver or kidney disease: Graviola can cause liver and kidney toxicity with repeated use.
You are having nuclear imaging: Graviola can reduce tissue uptake of radiopharmaceuticals used for diagnosis or treatment.

Side Effects
  • Movement disorders and myeloneuropathy (neuropathy that affects the myelin sheath), with symptoms similar to those of Parkinson's disease
E-mail your questions and comments to aboutherbs@mskcc.org.