Graviola (Annona muricata)
Graviola is a tree prevalent in the rain forests of Africa, South America, and Southeast Asia. Graviola has a long, rich history of use in herbal medicine as well as a lengthy recorded indigenous use.
All parts of the graviola tree are used in natural medicine in the tropics, including the bark, leaves, roots, fruit, and fruit seeds. Different properties and uses are attributed to the different parts of the tree. Generally, the fruit and fruit juice are taken for worms and parasites, to cool fevers, to increase mother’s milk after childbirth, and as an astringent (drying agent) for diarrhea and dysentery. The crushed seeds are used against internal and external parasites, head lice, and worms. The bark, leaves, and roots are considered antispasmodic, hypotensive, and sedative, and a tea is made for various disorders toward those effects.
In the Peruvian Andes, a leaf tea is used for catarrh (inflammation of mucous membranes) and the crushed seed is used to kill parasites. In the Peruvian Amazon the bark, roots, and leaves are used for diabetes and as a sedative and antispasmodic. Indigenous tribes in Guyana use a leaf and/or bark tea as a sedative and heart tonic. In the Brazilian Amazon a leaf tea is used for liver problems, and the oil of the leaves and unripe fruit is mixed with olive oil and used externally for neuralgia, rheumatism, and arthritis pain. In Jamaica, Haiti, and the West Indies, the fruit and/or fruit juice is used for fevers, parasites, and diarrhea; the bark or leaf is used as an antispasmodic, sedative, and nervine for heart conditions, coughs, flu, difficult childbirth, asthma, hypertension, and parasites.
Today, in the United States and Europe, graviola is sold as a popular adjunctive natural therapy for cancer. This use has stemmed from published research on graviola and its naturally occurring chemicals possessing anticancerous actions, rather than its established traditional uses in South America.
Many active compounds and chemicals have been found in graviola, as scientists have been studying its properties since the 1940s. Graviola produces these natural compounds in its leaf and stem, bark, and fruit seeds. Most of the research on graviola focuses on a novel set of chemicals called Annonaceous acetogenins. Chemically, they are derivatives of long-chain fatty acids. Annonaceous acetogenins are only found in the Annonaceae family (to which graviola belongs). These chemicals in general have been documented with antitumorous, antiparasitic, insecticidal, and antimicrobial activities.The Annonaceous acetogenins discovered in graviola thus far include: annocatalin, annohexocin, annomonicin, annomontacin, annomuricatin A and B, annomuricin A through E, annomutacin, annonacin, annonacinone, annopentocin A through C, cis-annonacin, ciscorossolone, cohibin A through D, corepoxylone, coronin, corossolin, corossolone, donhexocin, epomuricenin A and B, gigantetrocin, gigantetrocin Aand B, gigantetrocinone, gigantetronenin, goniothalamicin, iso-annonacin, javoricin, montanacin, montecristin, muracin A through G, muricapentocin, muricatalicin, muricatalin, muri-catenol, muricatetrocin A and B muricatin D, muricatocin A through C muricin H, muricin I, muricoreacin, murihexocin 3, murihexocin A through C, murihexol, murisolin, robustocin, rolliniastatin 1 & 2, saba-delin, solamin, uvariamicin I and IV, and xylomaticin.
There has been extensive research on graviola over the last three decades. Studies over the years have validated some of graviola’s many uses in herbal medicine. Several early studies demonstrated that the bark as well as the leaves had hypotensive, antispasmodic, anticonvulsant, vasodilator, smooth-muscle relaxant, and cardiodepressant activities in animals. Researchers verified graviola leaf’s hypotensive properties in rats again in 1991. Several studies over the years have demonstrated that leaf, bark, root, stem, and seed extracts of graviola are antibacterial in vitro against numerous pathogens, and that the bark has antifungal properties.
Graviola seeds demonstrated active antiparasitic properties in a 1991 study, which validated its long-standing traditional use, and a leaf extract showed to be active against malaria in two other studies (in 1990 and 1993). The leaves, root, and seeds of graviola demonstrated insecticidal properties, with the seeds demonstrating strong insecticidal activity in an early 1940 study. In a 1997 clinical study, novel alkaloids found in graviola fruit exhibited antidepressive effects in animals.
Research has confirmed that Annonaceous acetogenins have significant antitumorous properties and selective toxicity against various types of cancer cells (without harming healthy cells). Mode of action studies in three separate laboratories have recently determined that these acetogenins are superb inhibitors of enzyme processes that are only found in the membranes of cancerous tumor cells. Therefore, they are toxic to cancer cells but have no toxicity to healthy cells. Purdue University, in West Lafayette, Indiana, has conducted a great deal of the research on the acetogenins, much of which has been funded by The National Cancer Institute and/or the National Institutes of Health (NIH). Thus far, Purdue University and/or its staff have filed at least nine U.S. and/or international patents on their work around the antitumorous and insecticidal properties and uses of these acetogenins
In 1997, Purdue University published information with promising news that several of the Annonaceous acetogenins not only are effective in killing tumors that have proven resistant to anticancer agents, but also seem to have a special affinity for such resistant cells.
An animal study published by Wang L.Q. et. al. found various acetogenins exhibited antitumor activity in mice. First, they inoculated mice with lung cancer cells. Then, one third received nothing (the control group), one third received the chemotherapy drug adriamycin, and one third received the main graviola acetogenin, annonacin (at a dosage of 10 mg/kg). At the end of two weeks, five of the six in the untreated control group were still alive and lung tumor sizes were then measured. The adriamycin group showed a 54.6 percent reduction of tumor mass over the control group, but 50 percent of the animals had died from toxicity (three of six). The mice receiving annonacin were all still alive, and the tumors were inhibited by 57.9 percent—slightly better than adriamycin and without toxicity. This led the researchers to summarize: “This suggested that annonacin was less toxic in mice. On considering the antitumor activity and toxicity, annonacin might be used as a lead to develop a potential anticancer agent.”
Annonaceous acetogenins isolated from the leaves, bark, and twigs are among the active constituents. Graviola-induced cell death inhibited by glucose supplementation suggests energy depletion. Graviola has also been shown to stimulate serotonin receptors. 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.
In animal models, antidiabetic effects are due to antioxidant, hypolipidemic, and protective effects in pancreatic beta-cells, which improves glucose metabolism. Antiulcer effects may occur via increased nitric oxide and prostaglandin E2 activities. Anti-inflammatory and analgesic actions with a fruit extract occurred via COX-1/2 inhibition and the blocking of opioid receptors.
Graviola extracts were effective against adriamycin-resistant human mammary adenocarcinoma by blocking ATP access and inhibiting plasma membrane glycoprotein. Inhibition of HIF-1α, NF-κB, glucose transporters, and glycolytic enzymes also decreased glucose uptake and ATP production in pancreatic cancer cells. In breast cancer cells, EGFR expression was downregulated, and free-radical scavenging occurred. In colon and in lung cancer cell lines, G1 cell-cycle arrest occurred by upregulating Bax and downregulating Bcl-2 proteins.
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