Graviola

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Graviola

Common Names

  • Guanabana
  • Soursop
  • Custard apple
  • Brazilian paw paw

For Patients & Caregivers

How It Works

Graviola showed anticancer effects in lab studies, but human data are lacking.

In lab experiments, graviola extracts appear to be effective against some types of viruses, bacteria, parasites, and cancer cells. Chemicals called acetogenins are thought to be the major active compound. However in lab and animal experiments, substances derived from graviola damaged nerve cells and caused neurological side effects similar to Parkinson’s disease. Other animal studies suggest long-term use may increase the risk of neurological diseases. Whether this translates to similar effects in humans is unclear, so more studies are needed to determine safety and efficacy.

Of note, animal studies suggest graviola may affect nuclear imaging because it has been shown to decrease the uptake of radiopharmaceuticals used in such procedures. Therefore, patients should discuss the use of this product with their healthcare practitioners.

Purported Uses
  • To treat cancer
    Lab studies suggest that graviola may be effective against some types of cancer cells, but human studies are lacking.
  • To fight infections
    Lab studies suggest that graviola may prevent certain infections, but human studies are lacking.
Do Not Take If

You are undergoing medical imaging: Animal studies suggest graviola may affect nuclear imaging because it may decrease the uptake of radiopharmaceuticals used in such procedures.
You are taking blood pressure medications: Animal studies suggest graviola has blood pressure-lowering effects, so it may have additive effects when taken with these drugs. Clinical relevance has yet to be determined.
You are taking diabetic medications: Animal studies suggest graviola has blood sugar-lowering effects, so it may have additive effects when taken with these drugs. Clinical relevance has yet to be determined.

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For Healthcare Professionals

Scientific Name
Annona muricata
Clinical Summary

Graviola is a tree prevalent in the rain forests of Africa, South America, and Southeast Asia. The fruits, also known as soursop, are consumed as food. The leaves and stems are used in traditional medicine for symptoms associated with inflammation and infection. Graviola is also available as a dietary supplement and widely promoted as an alternative treatment for cancer, although clinical evidence is lacking. In some Caribbean countries, it is one of the common herbal remedies used among prostate, breast, and colorectal cancer patients (33).

Perceived health benefits of graviola are attributed to its antioxidant properties (1) (2) (3) (4). In animal models, graviola extracts showed anti-inflammatory (5), analgesic (6), antidiabetic (7), antiulcer (8), and antiviral (9) effects. The leaf extracts also have antimicrobial activities (10) (11).

Lab studies have also evaluated extracts from the graviola leaf, fruit, and seed for their anticancer effects. Some of these studies suggest activity against breast (16), lung (12), colon (13), prostate (14), pancreatic (15), liver (17), and skin cancer (18) cell lines, but human studies are lacking. In addition, it is unclear whether the neurotoxicity identified in preclinical studies may translate to humans, as one systematic review suggests a favorable profile with graviola leaf extract (36), so more studies are needed to determine safety and efficacy.

Purported Uses
  • Cancer
  • Infections
Mechanism of Action

Annonaceous acetogenins isolated from the leaves, bark, and twigs are among the active constituents (35). Graviola-induced cell death inhibited by glucose supplementation suggests energy depletion (20). Graviola has also been shown to stimulate serotonin receptors (24). Cell-stimulating behaviors may occur either by increased mitochondrial turnover or by preparation to leave the G1 phase, possibly through a promitotic stimulus present within the extract which acts like a growth factor (28).

In animal models, antidiabetic effects are due to antioxidant, hypolipidemic, and protective effects in pancreatic beta-cells, which improves glucose metabolism (7). Antiulcer effects may occur via increased nitric oxide and prostaglandin E2 activities (8). Anti-inflammatory and analgesic actions with a fruit extract occurred via COX-1/2 inhibition and the blocking of opioid receptors (5).

Graviola extracts were effective against adriamycin-resistant human mammary adenocarcinoma by blocking ATP access and inhibiting plasma membrane glycoprotein (29). Inhibition of HIF-1α, NF-κB, glucose transporters, and glycolytic enzymes also decreased glucose uptake and ATP production in pancreatic cancer cells (15). In breast cancer cells, EGFR expression was downregulated (16) and free-radical scavenging occurred (30). In colon and in lung cancer cell lines, G1 cell-cycle arrest occurred by upregulating Bax and downregulating Bcl-2 proteins (12) (13).

In vitro, graviola alkaloids caused movement disorders and myeloneuropathy with symptoms mimicking Parkinson’s disease (20) (21). Animal studies suggest that long-term ingestion of graviola juice promotes generation of reactive nitrogen species that may accelerate development of neurodegenerative diseases involving the microtubule-associated protein tau (34).

Herb-Drug Interactions

Antidiabetics: In a murine model, graviola showed hypoglycemic effects (31), and may have additive effects with antidiabetic drugs. Clinical relevance is not known.
Antihypertensives: In a murine model, graviola showed hypotensive effects (32), and may have additive effects with antihypertensive medications. Clinical relevance has yet to be determined.

Herb Lab Interactions

Nuclear imaging (radiopharmaceutical biodistribution): In animal models, graviola decreased uptake of radioactivity per gram of tissue in bladder, kidney, and blood (22).
Blood glucose test: In a murine model, graviola reduced blood glucose levels (31).
Blood pressure readings: In a murine model, graviola reduced blood pressure readings (32).

Dosage (OneMSK Only)
References
  1. George VC, Kumar DR, Suresh PK, et al. Antioxidant, DNA protective efficacy and HPLC analysis of Annona muricata (soursop) extracts. J Food Sci Technol. Apr 2015;52(4):2328-2335.
  2. Zamudio-Cuevas Y, Diaz-Sobac R, Vazquez-Luna A, et al. The antioxidant activity of soursop decreases the expression of a member of the NADPH oxidase family. Food Funct. Feb 2014;5(2):303-309. 
  3. Gavamukulya Y, Abou-Elella F, Wamunyokoli F, et al. Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola). Asian Pac J Trop Med. Sep 2014;7s1:S355-363.
  4. Lee YH, Choo C, Watawana MI, et al. An appraisal of eighteen commonly consumed edible plants as functional food based on their antioxidant and starch hydrolase inhibitory activities. J Sci Food Agric. 2015 Nov;95(14):2956-64.
  5. Ishola IO, Awodele O, Olusayero AM, et al. Mechanisms of analgesic and anti-inflammatory properties of Annona muricata Linn. (Annonaceae) fruit extract in rodents. J Med Food. Dec 2014;17(12):1375-1382.
  6. 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.
  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.
  8. Moghadamtousi SZ, Rouhollahi E, Karimian H, et al. Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement. Drug Des Devel Ther. 2014;8:2099-2110.
  9. 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.
  10. Mohd Abd Razak MR, Afzan A, Ali R, et al. Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum. BMC Complement Altern Med. 2014;14(1):492.
  11. Jaramillo MC, Arango GJ, Gonzalez MC, et al. Cytotoxicity and antileishmanial activity of Annona muricata pericarp. Fitoterapia. Apr 2000;71(2):183-186.
  12. Moghadamtousi SZ, Kadir HA, Paydar M, et al. Annona muricata leaves induced apoptosis in A549 cells through mitochondrial-mediated pathway and involvement of NF-kappaB. BMC Complement Altern Med. 2014;14:299.
  13. Zorofchian Moghadamtousi S, Karimian H, Rouhollahi E, et al. Annona muricata leaves induce G(1) cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells. J Ethnopharmacol. Oct 28 2014;156:277-289.
  14. Asare GA, Afriyie D, Ngala RA, et al. Antiproliferative activity of aqueous leaf extract of Annona muricata L. on the prostate, BPH-1 cells, and some target genes. Integr Cancer Ther. Jan 2015;14(1):65-74.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. Pieme CA, Kumar SG, Dongmo MS, et al. Antiproliferative activity and induction of apoptosis by Annona muricata (Annonaceae) extract on human cancer cells. BMC Complement Altern Med. 2014;14(1):516.
  20. 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.
  21. 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.
  22. 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. 
  23. 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.
  24. Roman G. Tropical myeloneuropathies revisited. Curr Opin Neurol. Oct 1998;11(5):539-544.
  25. Chen Y, Chen JW, Zhai JH, et al. Antitumor activity and toxicity relationship of annonaceous acetogenins. Food Chem Toxicol. Aug 2013;58:394-400.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. Clement YN, Mahase V, Jagroop A, et al. Herbal remedies and functional foods used by cancer patients attending specialty oncology clinics in Trinidad. BMC Complement Altern Med. Oct 21 2016;16(1):399.
  34. Rottscholl R, Haegele M, Jainsch B, et al. Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice. J Neurochem. Nov 2016;139(4):624-639.
  35. Qazi AK, Siddiqui JA, Jahan R, et al. Emerging therapeutic potential of graviola and its constituents in cancers. Carcinogenesis. Apr 5 2018;39(4):522-533.
  36. Chan WJ, McLachlan AJ, Hanrahan JR, et al. The safety and tolerability of Annona muricata leaf extract: a systematic review. J Pharm Pharmacol. Jan 2020;72(1):1-16.
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