integrative medicine : graviola

Scientific Name Annona muricata Top Common Name

Guanabana, soursop, custard apple, brazilian paw paw Top 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). Top Purported Uses

Cancer treatment
Parasitic infections

Top Constituents

Acetogenins: annosquamin B, bullatacin, annosquatin B, annonacin, annonacin A and annomuricin A muricins J, K, and L
Quinolines and isoquinolines
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
(3) (13) (14) (16) (17) (18) (19) (20)

Top 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). Top Warnings

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

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

Movement disorders and myeloneuropathy with symptoms mimicking Parkinson's disease (13) (14) Top Herb-Drug Interactions

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

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02 October 2014

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