Billion-dollar Drug Company Nearly Squashes Astounding Research on Natural Cancer Killer

Do you know some one who is dying of  Cancer…….

The big C

 Lung cancer, colon cancer, skin Cancer breast cancer, prostate cancer, and pancreatic cancer;

Tell them about Graviola

Paw Paw Tv

Subscribe to a FREE Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on various supplements and natural medicine topics, and their practical interpretation by Ray Sahelian, M.D. We will discuss graviola cancer research as more information becomes available.

What's in Graviola?
There are quite a number of compounds in graviola with exotic and long names. Some of these include acetogenins, muricins, and many others.

Graviola and Cancer
Although laboratory research with graviola and cancer looks promising, little is known about the role graviola supplements would play in human cancer prevention or treatment. Therefore, at this point, the role of graviola and cancer in humans in unclear.

Graviola Extract
I have heard that some companies sell a graviola extract, but whether a graviola extract offers benefits beyond that of regular graviola whole powder is not known.

Graviola Research Update
Proximate composition and selected physicochemical properties of the seed, pulp and oil of sour sop (Annona muricata - graviola ).
Plant Foods Hum Nutr. 2002 Spring;57(2):165-71.
Proximate composition and physicochemical analyses were carried out on the seed, pulp and extracted oil of sour sop ( graviola ). The results showed that the graviola seed contained 8.5% moisture, 2.4% crude protein, 13.6% ash, 8.0% crude fiber, 20.5% fat and 47.0% carbohydrate. The graviola seed also contained 0.2% water soluble ash, 0.79% titratable acidity and 17.0 mg calcium/100 g. The graviola pulp was found to contain 81% moisture, 3.43% titratable acidity and 24.5% non-reducing sugar. Selected physicochemical characteristics included refractive indices of 1.335 for the graviola seed and 1.356 for the pulp, pH values of 8.34 for the graviola seed and 4.56 for the pulp, and soluble solids contents of 1.5 degrees Brix for the graviola seed and 15 degrees Brix for the pulp.

Effect of the extract of Annona muricata ( graviola extract ) and Petunia nyctaginiflora on Herpes simplex virus.
J Ethnopharmacol. 1998 May;61(1):81-3.
Annona muricata (graviola) and Petunia nyctaginiflora (Solanaceae) were screened for their activity against Herpes simplex virus-1 (HSV-1) and clinical isolate (obtained from the human keratitis lesion). We have looked at the ability of extract(s) to inhibit the cytopathic effect of HSV-1 on vero cells as indicative of anti-HSV-1 potential. The minimum inhibitory concentration of ethanolic extract of graviola and aqueous extract of P. nyctaginiflora was found to be 1 mg/ml.

Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe.
J Neurochem. 2004 Jan;88(1):63-9.
In Guadeloupe, epidemiological data have linked atypical parkinsonism with fruit and herbal teas from plants of the Annonaceae family, particularly Annona muricata (graviola). These plants contain a class of powerful, lipophilic complex I inhibitors, the annonaceous acetogenins. To determine the neurotoxic potential of these substances, we administered annonacin, the major acetogenin of graviola, to rats intravenously with Azlet osmotic minipumps (3.8 and 7.6 mg per kg per day for 28 days). Annonacin inhibited complex I in brain homogenates in a concentration-dependent manner, and, when administered systemically, entered the brain parenchyma, where it was detected by matrix-associated laser desorption ionization-time of flight mass spectrometry, and decreased brain ATP levels by 44%. In the absence of evident systemic toxicity, we observed neuropathological abnormalities in the basal ganglia and brainstem nuclei. Stereological cell counts showed significant loss of dopaminergic neurones in the substantia nigra (-31.7%), and cholinergic (-37.9%) and dopamine and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive GABAergic neurones (-39.3%) in the striatum, accompanied by a significant increase in the number of astrocytes (35.4%) and microglial cells (73.4%). The distribution of the lesions was similar to that in patients with atypical parkinsonism. These data are compatible with the theory that annonaceous acetogenins, such as annonacin, might be implicated in the aetiology of Guadeloupean parkinsonism and support the hypothesis that some forms of parkinsonism might be induced by environmental toxins.

The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism.
Neuroscience. 2003;121(2):287-96.
The death of dopaminergic neurons induced by systemic administration of mitochondrial respiratory chain complex I inhibitors such as 1-methyl-4-phenylpyridinium (MPP(+); given as the prodrug 1-methyl-1,2,3,6-tetrahydropyridine) or the pesticide rotenone have raised the question as to whether this family of compounds are the cause of some forms of Parkinsonism. We have examined the neurotoxic potential of another complex I inhibitor, annonacin, the major acetogenin of Annona muricata (graviola), a tropical plant suspected to be the cause of an atypical form of Parkinson disease in the French West Indies (Guadeloupe). When added to mesencephalic cultures for 24 h, annonacin was much more potent than MPP(+) (effective concentration [EC(50)]=0.018 versus 1.9 microM) and as effective as rotenone (EC(50)=0.034 microM) in killing dopaminergic neurons. The uptake of [(3)H]-dopamine used as an index of dopaminergic cell function was similarly reduced. Toxic effects were seen at lower concentrations when the incubation time was extended by several days whereas withdrawal of the toxin after a short-term exposure (<6 h) arrested cell demise. Unlike MPP(+) but similar to rotenone, the acetogenin also reduced the survival of non-dopaminergic neurons. Neuronal cell death was not excitotoxic and occurred independently of free radical production. Raising the concentrations of either glucose or mannose in the presence of annonacin restored to a large extent intracellular ATP synthesis and prevented neuronal cell demise. Deoxyglucose reversed the effects of both glucose and mannose. Other hexoses such as galactose and fructose were not protective. Attempts to restore oxidative phosphorylation with lactate or pyruvate failed to provide protection to dopaminergic neurons whereas idoacetate, an inhibitor of glycolysis, inhibited the survival promoting effects of glucose and mannose indicating that these two hexoses acted independently of mitochondria by stimulating glycolysis. In conclusion, our study demonstrates that annonacin promotes dopaminergic neuronal death by impairment of energy production. It also underlines the need to address its possible role in the etiology of some atypical forms of Parkinsonism in Guadeloupe.

Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe.
In the French West Indies there is an abnormally high frequency of levodopa-resistant parkinsonism, suggested to be caused by consumption of fruit and infusions of tropical plants, especially Annona muricata (graviola). To determine whether toxic substances from this plant can cause the neuronal degeneration or dysfunction underlying the syndrome, we exposed mesencephalic dopaminergic neurons in culture to the total extract (totum) of alkaloids from Annona muricata root bark and to two of the most abundant subfractions, coreximine and reticuline. After 24 hours, 50% of dopaminergic neurons degenerated with 18 microg/ml totum, 4.3 microg/ml (13 microM) coreximine, or 100 microg/ml (304 microM) reticuline. The effects of the alkaloid totum were not restricted to the population of dopaminergic cells since GABAergic neurons were also affected by the treatment. Nuclei in dying neurons showed DNA condensation or fragmentation, suggesting that neuronal death occurred by apoptosis. Cell death was not excitotoxic and did not require toxin uptake by the dopamine transporter. Neurodegeneration was attenuated by increasing the concentration of glucose in the culture medium, which also reduced the effect of the dopaminergic neurotoxin MPP+, a mitochondrial respiratory chain inhibitor. Toxin withdrawal after short-term exposure arrested cell death. Acute treatment with totum, coreximine, or reticuline reversibly inhibited dopamine uptake by a mechanism that was distinct from that causing neuronal death. GABA uptake was not reduced under the same conditions. This study suggests that alkaloids from graviola can modulate the function and the survival of dopaminergic nerve cells in vitro. It is therefore conceivable that repeated consumption could cause the neuronal dysfunction and degeneration underlying the West Indian parkinsonian syndrome.

Cytotoxicity and antileishmanial activity of Annona muricata pericarp - graviola.
Fitoterapia. 2000 Apr;71(2):183-6.
Hexane, ethyl acetate and methanol extracts of Annona muricata pericarp ( graviola ) were tested in vitro against Leishmania braziliensis and L. panamensis promastigotes, and against cell line U-937. The ethyl acetate graviola extract was more active than the other extracts and even of Glucantime used as reference substance. Its fractionation led to the isolation of three acetogenins--annonacin, annonacin A and annomuricin A.

Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata - graviola.
J Nat Prod. 1998 Apr;61(4):432-6.
Bioactivity-directed fractionation of the leaf extract of Annona muricata L. (graviola) has resulted in the isolation of two new Annonaceous acetogenins, annomuricine (1) and muricapentocin (2). Compounds 1 and 2 are monotetrahydrofuran ring acetogenins bearing two flanking hydroxyl groups; however, each has three additional hydroxyl groups. Compound 1 has an erythro 1,2-diol, and 2 has a 1,5,9-triol moiety. Both 1 and 2 showed significant cytotoxicities against six types of human tumors, with selectivities to the pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines. Graviola research.

Isoquinoline derivatives isolated from the fruit of Annona muricata ( graviola ) as 5-HTergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products.
J Pharm Pharmacol. 1997 Nov;49(11):1145-9.
Extracts of the graviola plant have been shown to inhibit binding of [3H]rauwolscine to 5-HTergic 5-HT1A receptors in calf hippocampus, and three alkaloids, annonaine (1), nornuciferine (2) and asimilobine (3), isolated from the fruit have been shown to have IC50 values of 3 microM, 9 microM and 5 microM, respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. These results imply that the fruit of graviola possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3, and that in the past potent leads for the development of anti-depressive therapeutics have not been used.

Five new monotetrahydrofuran ring acetogenins from the leaves of Annona muricata - graviola.
J Nat Prod. 1996 Nov;59(11):1035-42.
Bioactivity-directed fractionation of the leaves of Annona muricata (graviola) resulted in the isolation of annopentocins A (1), B (2), and C(3), and cis- and trans-annomuricin-D-ones (4, 5). Compounds 1-3 are the first acetogenins reported bearing a mono-tetrahydrofuran (THF) ring with one flanking hydroxyl, on the hydrocarbon side, and another hydroxyl, on the lactone side, that is one carbon away from the THF ring. Compounds 4 and 5 from graviola were obtained in a mixture and are new mono-THF ring acetogenins bearing two flanking hydroxyls and an erythro-diol located between the THF and the ketolactone rings. Compound 1 was selectively cytotoxic to pancreatic carcinoma cells (PACA-2), and 2 and 3 were selectively cytotoxic to lung carcinoma cells (A-549); the mixture of 4 and 5 was selectively cytotoxic for the lung (A-549), colon (HT-29), and pancreatic (PACA-2) cell lines with potencies equal to or exceeding those of Adriamycin. Graviola anti-cancer benefits.

Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata (graviola).
J Nat Prod. 1996 Feb;59(2):100-8.
Bioactivity-directed fractionation of the seeds of Annona muricata L. (graviola) resulted in the isolation of five new compounds: cis-annonacin (1), cis-annonacin-10-one (2), cis-goniothalamicin (3), arianacin (4), and javoricin (5). Three of these (1-3) are among the first cis mono-tetrahydrofuran ring acetogenins to be reported. NMR analyses of published model synthetic compounds, prepared cyclized formal acetals, and prepared Mosher ester derivatives permitted the determinations of absolute stereochemistries. Bioassays of the pure graviola compounds, in the brine shrimp test, for the inhibition of crown gall tumors, and in a panel of human solid tumor cell lines for cytotoxicity, evaluated relative potencies. Compound 1 from graviola was selectively cytotoxic to colon adenocarcinoma cells (HT-29) in which it was 10,000 times the potency of adriamycin.

Muricatocins A and B, two new bioactive monotetrahydrofuran Annonaceous acetogenins from the leaves of Annona muricata (graviola).
J Nat Prod. 1995 Jun;58(6):902-8.
The leaves of Annona muricata (graviola) have yielded the novel monotetrahydrofuran Annonaceous acetogenins, muricatocins A [1] and B [2]. Each compound possesses five hydroxyl groups, with two hydroxyl groups at the C-10 and C-12 positions. The absolute configurations of 1 and 2 (except for positions C-10 and C-12) were determined by Mosher ester methodology. The C-10, C-12 acetonides (1c, 2c) suggested relative stereochemistry and significantly enhanced cytotoxicity against the A-549 human lung tumor cell line. Three known monotetrahydrofuran acetogenins, annonacin A, (2,4-trans)-isoannonacin, and (2,4-cis)-isoannonacin, were also found from graviola.

Two new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annomuricins A and B, from the leaves of Annona muricata (graviola).
J Nat Prod. 1995 Jun;58(6):830-6.
The leaves of graviola have yielded eight monotetrahydrofuran Annonaceous acetogenins. Two of them, annomuricins A [1] and B [2], whose chemical structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, are novel and unusual. Compounds 1 and 2 each possess five hydroxyl groups; two hydroxyl groups are vicinal, with the vicinal group of 1 threo and that of 2 erythro. The absolute configurations of 1 and 2 were determined by Mosher ester methodology. Six monotetrahydrofuran acetogenins, previously described in the graviola seeds, were found in the graviola leaves; these are gigantetrocin A, annonacin-10-one, muricatetrocins A and B, annonacin, and goniothalamicin.

Screening of Brazilian fruit aromas using solid-phase microextraction-gas chromatography-mass spectrometry.
J Chromatogr A. 2000 Mar 17;873(1):117-27.
Manual headspace solid-phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS) was used for the qualitative analysis of the aromas of four native Brazilian fruits: cupuassu (Theobroma grandiflorum, Spreng.), caja (Spondias lutea. L.), siriguela (Spondias purpurea, L.) and graviola (Anona reticulata, L). Industrialized pulps of these fruits were used as samples, and extractions with SPME fibers coated with polydimethylsiloxane, polyacrylate, Carbowax and Carboxen were carried out. The analytes identified included several alcohols, esters, carbonyl compounds and terpernoids. The highest amounts extracted, evaluated from the sum of peak areas, were achieved using the Carboxen fiber.

Graviola fruit concerns
As you can read in detail in the research updates above, there is a concern that consuming the graviola fruit for prolonged periods (many years in a row or perhaps a lifetime) may increase the risk for a form of Parkinson's Disease. This is not known for certain at this time but to be cautious, it would be best to take holidays from use of graviola and not eat the fruit for months at a time without a break.

Graviola Emails
Two years ago my nephew was scheduled for surgery after a positive biopsy for prostrate cancer. While awaiting surgery he took Graviola for two months. His tumors disappeared and his PSA dropped to 2 and his surgery was cancelled. His checkups remain fine. His PSA is now less than 2.Thanks for your excellent site detailing reliable information about many complementary health supplements. I have benefited by reading many articles that you publish.

I came across your entry about Graviola. In March of 2003 I met Dr. Jerry McLaughlin, emeritus professor of pharmacognosy of Purdue. Dr. McLaughlin lectured about his work with the Annonaceous acetogenins. Among these are the molecules from Annona muricata (graviola) and
Asimina triloba (paw paw). He distinguished these species mainly because of the difference in bioassay activity and the difference in tumor inhibition in mice. He reported on a human trial in the US of an extract from Asimina triloba (paw paw) that had 94 participants with diagnosed cancer. Later that year, I videotaped his lecture. I then posted the parts on an educational website called pawpaw.tv. Although he is the former editor of the Journal of Natural Products and has published 70 papers in peer-reviewed journals concerning Annonaceous acetogenins, he has not had success thus far in finding a publisher. I wanted you to be aware that there is a significant difference in activity levels of the double ring compounds (e.g. bullatacin) found in Asimina triloba, and the single ring compounds found in Annona muricata (annonacin). Much of the popular writing from sources on the internet fails to distinguish the difference. This causes a misleading information to be put forward about the biological use of the two herbs. You may with to refer to his published review of Annonaceous acetogenins found in the 1999 Journal of Natural Products. My website
www.pawpaw.tv has his lecture and some written information about his research.

graviola research - Soursops (Annona muricata L.) are highly aromatic fruits with white juicy flesh and are native to tropical North and South America.


 
HSI first told the full story behind GRAVIOLA
ALMOST FIVE YEARS AGO...

NOW - YOU AND YOUR ONCOLOGIST
CAN FINALLY GET THE COMPLETE REPORT!

See the original research that proves
Graviola's 10,000 times stronger than chemotherapy
withno adverse side effects

Just when you thought we covered everything there was to know about Graviola...now there's even more to prove that it's perhaps the world's ultimate cancer-fighter!

That's right. For the first time, we're able to offer you all the original research about this amazing cancer-buster from the Amazon in one comprehensive report.

Studies in the 'Graviola Technical Report' span four decades and three continents. As you'll see, in at least 20 laboratory tests since the 1970s, Graviola's been proven to:

Hunt down and kill cancer cells in the prostate, lung, breast, colon and pancreas
Leave healthy cells completely unharmed
Boost your immune system without causing nausea, hair loss, or weight loss.
This report is a 'must-have' for anyone battling cancer who is considering Graviola as a complement to their traditional course of treatment.

You'll read the complete details of one recent study conducted at Catholic University of South Korea. Scientists discovered that two chemicals extracted from Graviola seeds targeted and killed malignant breast and colon cells in a test tube.

Plus...you'll read the study that proved...



Graviola is 10,000 times stronger than chemo

In another study, published in the Journal of Natural Products, scientists proved that Graviola dramatically outperforms one of the most common chemotherapy drugs on the market. You'll have all the scientific evidence that showed one chemical in Graviola selectively kills colon cancer cells at "10,000 times the potency of Adriamycin."

 
Other promising and ongoing research at Purdue University is supported by a grant from the National Cancer Institute. Purdue researchers recently found that leaves from the Graviola tree kills cancer cells "among six human-cell lines" and are especially effective against prostate and pancreatic cancer cells.

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