Annona Muricata

Author: alessandra volpe
Date: 01/02/2012



It's a member of the family of Custard apple trees called Annonaceae. Annona muricata produces fruits that are usually called graviola or soursop due to its slightly acidic taste when ripe. Trees grew natively in the Caribbean and Central America.
It has been used in traditional medicine in many countries. Extracts of graviola show antiviral, antinociceptive, anti-inflammatory and antihyperglycemic properties. Graviola is also effective against multidrug resistant cancer cells line. Alkaloids extracted from graviola may cause neuronal dysfunction and degeneration leading to symptoms of Parkinson’s disease.


These compounds are:
• Natural products from the plants of the family Annonaceae, collectively called Annonaceous acetogenins;
Quinolines and isoquinolines, aromatic organic base synthesized or obtained from coal tar and used as a food preservative and in making antiseptics;
Coreximine and reticuline
Also graviola is rich in VITAMINS B and C, and PHOSPHORUS. The fruit is high in LINOLEIC ACID and contains unsaturated fats.


Kingdom: Plantae
Order: Magnoliales
Family: Annonaceae
Genus: Annona
Species: A. muricata
Common name: soursop (US and the Caribbean); guanabana (Cuba, Caribbean); corosol (West Indies); katara ara tara (Cook Islands); laguana (Guam); sowasap (Nicaragua).


• Annonaceous acetogenins, phytochemicals isolated from the leaves, bark and twigs of graviola, are thought to be the active ingredients. The ethanolic extract of Annona muricata was found to inhibit the Herpes simplex virus and effective against many cancer cell lines.
• 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 the supplementation of glucose suggesting that cell death was caused by energy depletion.
• Graviola may have antidepressive activity due to its ability to stimulate serotonine receptors.

Antibacterial Activity

Antibacterial effects of aqueous and ethanolic extracts of pods of soursop were examined against Staphylococcus aureus, Vibrio cholerae and Escherichia coli .

The bioactivity of water-based soursop extracts against S. aureus and V. cholerae may be related to the chemical structure of the active substances. In an investigation of the bactericidal properties of eight species of annonaceae, it was confirmed the ability of trachylobanoic acid to inhibit S. aureus.
Annonaceae contain other bioactive substances, including a range of acetogenins with a wide spectrum of action, including antibiotic effects. Structurally, Annonaceous acetogenins are series of C-35/C-37 natural products derived from C-32/C-34 fatty acids and combined with a 2-propanol unit.

Abstract Antibacterial effect

Antinociceptive and Anti-ulcerogenic Activities

The antinociceptive activity of orally administered ethanol extract of Annona muricata leaf (AML) was demonstrated in mice and rats.
Acetic acid injected into peritoneal cavity is believed to be able lead to an increase of cyclooxygenase (COX) and lipooxygenase (LOX) products in peritoneal fluids as well as promoting the release of other inflammatory mediators such as bradykinin, substance P, TNF-α, IL-1β, IL-8, which finally stimulate the primary afferent nociceptors entering dorsal horn of the central nervous system.
The administration of the AML significantly reduced the number of abdominal writhing induced by acetic acid in a dose-dependent manner.
The result may suggest that the mechanism of AML may be partly mediated by the inhibition of COX and/or LOX and other inflammatory mediators in peripheral tissues. Also, the antinociceptive activity of AML could also be suggested by the interruption of signal transduction in primary afferent nociceptors.
Therefore it is suggested that AML may contain active ingredients which may act both centrally (via inhibition of central pain receptors) and peripherally (through inhibition of COX and/or LOX).

Besides that, it is well described that endogenous opioid system is largely involved in the central regulation of pain, as well as in the action of opioid-derived analgesic drugs. The present results exerted that the antinociception elicited by AML seems to be dependent of the activation of opioid system. The antinociceptive effect may due to the activation of opioid or central receptors or the modulation of the effect of endogenous opioid peptides which may participate in the antinociceptive activity at both peripheral and central levels.

In addition, AML has been observed to exhibit its antiulcerogenic effect in dose-dependent manner which relates to cytoprotective and antioxidant properties.

Gastric mucus acts as an important protective factor for the gastric mucosa. It is not only capable of acting as an antioxidant agent but also reducing mucosal damage mediated by oxygen free radicals. However, the protective properties of the mucus barrier depend on the gel structure and also on the amount or thickness of the layer covering the mucosal surface. Therefore, antiulcer agents should provoke mucosa-strengthening effect and cicatrisation action with low occurrence of side effects. This effect is known as cytoprotection.
AML have antioxidant effect and this could be one of the contributory factors in producing its anti-ulcerogenic effect.

In many studies, the control group treated orally with ethanol clearly produced the expected characteristic zone of necrotizing mucosal lesions. On the other hand, oral administration of AML significantly decreased the total lesion area and the percentage of lesion.
The preliminary phytochemical screening showed that the presence of tannins, flavonoids and triterpenes in AML may exert its effect in preventing gastric damage development on gastric mucosal.

Article Antinociceptive and Anti-ulcerogenic Activities

Antitumor Activity

Annonaceous acetogenins are a new class of compounds that have been reported to have potent cell growth inhibitory activities. These components have a wide range of clinical application for cancer chemotherapy.

First of all they are very potent inhibitors of the NADH-ubiquinone reductase (Complex I) activity of mammalian mitochondria.

The natural substances isolated from the seeds of Annona muricata are more potent of than rotenone and also piericidin (piericidin is the most powerful inhibitor of Complex I). These compounds belong to a group of bis-tetrahydrofuran acetogenins, amongst squamocin and otivarin behave qualitatively like rotenone, that prevents the transfer of electrons from Complex I to ubiquinone by blocking the ubiquinone-binding site.

Structure of squamocin

The inhibition of any step (in this case of the Complex I) in this process will halt the rest of the process. NADH is then no longer oxidized and the citric acid cycle ceases to operate because the concentration of NAD+ falls below the concentration that these enzymes can use.

An other way these chemical compouns can carry on their antitumor activity is inducing of reactive oxygen species (ROS) generation and reducing intracellular glutathione levels.

Oxidative stress induced by reactive oxygen intermediates including superoxide, hydrogen peroxide are known to cause apoptotic cell death in the pathogenesis of diverse human diseases, including cancer, diabetes and neurodegenerative disorders.

GSH is an anti-oxidant and decreased intracellular levels of GSH are associated with enhanced susceptibility to ROS mediated apoptosis.

In addition downregulation of Bcl-2 is known to sensitize the cells to apoptotic death. In fact the protooncogene Bcl-2 is known to inhibit apoptotic and necrotic cell death.

Abstract Antitumor Activity

Article Antitumor Activity

Anti Hyperglycemic Activity

Diabetes Mellitus (DM) is one of the most common metabolic disorders. It is estimated that in the year 2000, 171 million people had diabetes, and this is expected to double by year 2030.
Conventionally, insulin-dependant diabetes mellitus is treated with exogenous insulin and non insulin-dependant diabetes mellitus with synthetic oral hypoglycemic agents. However the hormone fails as a curative agent for complications of diabetes and synthetic oral drugs produce adverse health effects.

The bark, roots and leaves of Annona muricata has been reported to be used as anti-diabetes in the Peruvian Amazon. Many studies have confirmed the effects of methanolic extracts of A. muricata on glycemic control in streptozotocin -induced diabetic Wistar rats.

  • Photomicrograph of a normal (control) pancreatic islet showing cluster of β-cells which are centrally placed and peripherally placed α-cells

  • Photomicrograph of pancreatic islet of streptozotocin-induced diabetic rats showing degranulation (De) of β-cells and severe vacuolation (V) of the pancreatic islets

  • Photomicrograph of pancreatic islets of A.muricata treated diabetic rat showing recovery of the β- cells. As it is evident, the islet cells are regenerated, the inflammatory infiltration has disappeared and there is reduction in the vacuolation cased by administration of STZ

Streptozotocin-induced hyperglycemia in rats is considered a good model for the preliminary screening of agents active against type II diabetes and is widely used. It is a potent DNA methylating agent and act as a nitric oxide donor in pancreatic islet cells.

The treatment with extracts of A. muricata shows a significant antihyperglycemic activity in STZ-induced diabetic rats at the end of the experiment. It has been suggested that bioactive compounds from plants sources having antihyperglycemic activities might act by several mechanisms such as stimulating insulin secretion, increasing repair or proliferation of β-cells and enhancing the effects of insulin and adrenalin.

Article Anti Hyperglycemic Activities


In Guadeloupe, there is an abnormally high frequency of atypical parkinsonism. This pathology has been associated with the consumption of anonaceous plants that contain acetogenins, potent lipophilic inhibitors of complex I of the mitochondrial respiratory chain.
These compouns are reported to be more toxic than rotenone to mesencephalic neurons.

To test the hypothesis that annonacin, a prototypical acetogenin, contributes to the etiology of the disease, it was investigated whether annonacin affects the cellular distribution of the protein tau.

The treatment with annonacin has produced a concentration-dependent decrease in ATP levels, a redistribution of protein tau from the axons to the cell body, and cell death. Annonacin induced the retrograde transport of mitochondria, some of which had tau attached to their outer membrane.
The accumulation of tau in cell bodies is the neuropathological hallmark of a group of neurodegenerative disorders termed tauopathies.

Annonacin induces an increase in tau protein levels, which appears to result from reduced degradation rather than increased expression, because tau mRNA is reduced at the same annonacin concentration.

In summary annonacin-induced ATP reduction, but not ROS increase, and a redistribution of tau are associated with neurotoxicity.

Abstract Side Effects

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