Graviola / Annona muricata

Weer een nieuw natuurlijk en wonderbaarlijk kankermiddel. Ik word er niet meer enthousiast over, eerder depressief. Lees de verschillende meningen hier over in Bliss, IOCOB en anderen.

Graviola, de genezende kracht van het Braziliaanse regenwoud. (Bliss)
Annona muricata
Graviola is een groenblijvende boom, 5-6 m hoog, met grote, glanzende, donkergroene bladeren. Hij produceert hartvormige, eetbare vruchten met een doorsnede van 15-30 cm die 2 à 3 kg kunnen wegen. De rijpe Graviola vruchten bevatten lichtgeel-groene vruchtvlees met een zachte, romige en smeuïge, licht zuurzoete smaak. Graviola sap gebruikt men veelvuldig als basis voor een verfrissende smoothie of vruchtenshake met yoghurt of rijstmelk. Je kan, net zoals de inheemse bevolking in en rond de Amazone, er een heerlijke sorbet, ijs of cocktail van maken.

Graviola heeft een lange, rijke geschiedenis in de kruidengeneeskunde waarbij alle delen van de Graviola boom worden gebruikt. Verschillende eigenschappen en toepassingen worden toegeschreven aan de verschillende delen van de boom. Over het algemeen worden de vruchten en het vruchtensap ingezet tegen wormen en parasieten, om af te koelen bij koorts, om de moedermelk te verhogen na de bevalling en bij diarree en dysenterie.
De geplette zaden worden gebruikt om inwendig en uitwendig parasieten te doden. Ook wordt het ingezet tegen hoofdluis en wormen. In de Peruaanse Andes worden de bladeren gebruikt tegen ontsteking van de slijmvliezen. In de Peruaanse Amazone worden de schors, bladeren en wortels gebruikt tegen diabetes én als zenuwkalmerend middel voor het hart, tegen het hoesten, bij een moeilijke bevalling, tegen astma
en hoge bloeddruk.
In het Braziliaanse Amazonegebied wordt een thee van het bladgebruikt tegen leverproblemen. De olie van de bladeren en de onrijpe vrucht wordt gemengd met olijfolie en uitwendig gebruikt voor neuralgie, reuma, artritis en pijn.

Graviola Wetenschappelijke studies
Veel van de inheemse toepassingen van Graviola zijn onderbouwd door wetenschappelijk onderzoek. Het kalmerende effect op het lichaam is gekoppeld aan het vermogen om de bloeddruk te verlagen. Daarnaast bevat de vrucht ‘a serotonin uptake inhibitor’, een serotonine heropname remmer (SRI’s). Serotonine een neurotransmitter is betrokken in de ervaring van vreugde

Annonacae acetogeninen
In 1976 vond voor het eerst onderzoek plaats in opdracht van ‘The American National Cancer Institute’. Verschillende onderzoekers zijn er intussen in geslaagd om Annonacae acetogeninen, uit de bladeren, twijgen, schors en zaden van de vrucht te isoleren. Acetogeninen zijn een bepaald type vetzuren, die bij ‘in-vitro’ onderzoek al bij een lage dosering selectief kankercellen vernietigen, terwijl ze de gezonde kankercellen ongehinderd laten. Tot nu toe zijn deze acetogeninen actief gebleken tegen diverse vormen van kanker: longkanker, borst tumoren, prostaatkanker, alvleesklierkanker, darmkanker, bepaalde vormen van lymfeklierkanker en medicijn resistente borstkanker.
In langdurig onderzoek kwam ook de werkzaamheid tegen medicijn resistente tumoren naar voren. Eén van de manieren waarop kankercellen resistentie kweken tegen medicijnen is door het maken van een pomp. Deze pomp is in staat medicijnen uit de kankercel te verwijderen voordat ze deze onschadelijk kunnen maken. Deze pomp gebruikt heel veel energie, uitgedrukt in ATP. Echter blijken acetogeninen een specifieke voorkeur te hebben om de toevoer van ATP in een kankercel te blokkeren, zodat de kankercel afsterft.

Ubiquinon oxidoreductase
De belangrijkste werking van de acetogeninen is dat ze de NADH reactie van ubiquinon oxidoreductase tegenhouden. Dit is een belangrijk enzym dat in complex I leidt tot fosforylering in de mitochondriën. Acetogeninen interfereren direct op de plaats waar ubiquinon katalysatie plaatsvindt binnen complex I en bij microbiële glucose dehydrogenase. Ze verhinderen de ubiquinon gelinkte NADH oxidase, kenmerkend voor het plasma membraan van kankercellen. Onderzoekers aan de Purdue Universiteit in de V.S. vonden 14 verschillende acetogeninen met deze krachtige ATP-remmende eigenschappen (waarvan sommige alleen in Graviola voorkomen). Van deze 14 acetogeninen waren er 13 krachtiger getest tegen medicijn resistente borsttumoren dan de gangbare medicijnen adriamycine, vincristine en vinblastine. •

Dit is een artikel uit het tijdschrift Bliss November 2011 maar lees ook verder een artikel op de website van IOCOB.

Kanker 'genezen' met Graviola uit het regenwoud (Annona muricata) IOCOB
Kijk eens wat er gebeurt als je in Google de woorden 'cancer cure' intypt. Je krijgt niet meteen al de zappers te zien van de net overleden, aan grootheidswaanzin lijdende, Hulda Clark met haar anti-kanker-machientjes, maar een van de eerste hits heeft als titel: Cancer Cure with Graviola Herb from Amazon Rainforest. Dan sta je toch wel weer even te kijken. Hoe is het toch mogelijk dat dit soort informatie geproduceerd wordt. Als er een plant in de Amazone groeit, en door de Indianen als geneeskrachtig opgevat wordt, betekent dat niet meteen dat deze plant klakkeloos kanker geneest. En de verdere Google tekst luidt: New herbal cancer cure with the graviola tree leaves from the Amazon rainforest. Discovered by the National Cancer Institute. Very effective cure for all.... 

En even verder op die website, die deze plant aanbeveelt ter genezing voor kanker, staan voor de leek indrukwekkende verhalen, en we citeren:
"Purdue University and/or its staff have filed at least 9 U.S. and/or international patents on their work around the antitumorous and insecticidal properties and uses of these acetogenins. Three separate research groups have isolated novel compounds in the seeds and leaves of graviola which have demonstrated significant anti-tumorous, anticancerous and selective toxicity against various types of cancer cells, publishing 8 laboratory studies on their findings. Much of Purdue University's research on annonaceous acetogenins was funded by the NCI and/or the NIH.
The head Purdue pharmacologist in Purdue's research explains that cancer cells that survive chemotherapy may develop resistance to the agent used against them as well as other, even unrelated, drugs (known as multi-drug resistance [MDR]). Purdue researchers reported that annonaceous acetogenins preferentially killed multi-drug resistant cancer cells because it blocked production of adenosine triphosphate (ATP). Purdue researchers found that leaves from the graviola tree killed cancer cells "among six human cell lines."En dan de wervende tekst eronder:

"Graviola is very aggressive at breaking up tumors. It appears that, as with many health problems, the body (in its wisdom) is trying to protect itself by creating a tumor to encase the toxins that can harm the body. Breaking up the tumor releases toxins back into the body, making the person feel very sick. When tumors are surgically removed, this also takes out the toxins which why this is the most effective medical treatment for cancer. "

Nu even enkele andere wetenschappelijke feiten.
Een Chinese preklinische groep liet zien dat stoffen uit deze plant kankercellen daadwerkelijk het leven moeilijk maken. [1][2] Dat waren studies in celkweken van jaren geleden, afkomstig van dezelfde onderzoeksgroep. Andere studies zijn niet te vinden. Laat staan dat er studies gedaan zijn naar de veiligheid en effectiviteit van deze plantenpreparaten bij patienten met kanker. Geen enkele klinische studie!

Hoe kan je dan in hemelsnaam een dergelijk plantenpreparaat aanbevelen als geneesmiddel tegen kanker? De veiligheid van deze plantenfamilie is bovendien helemaal niet zo vanzelfsprekend, want de ziekte van Parkinson zou een bijwerking kunnen zijn. [3] [4] Onderdelen van deze plant hebben in diermodellen een giftige werking op een deel van de hersenen dat betrokken is bij de ziekte van Parkinson! [5]
Je koopt een plantenpreparaat tegen de kanker, uit de Amazone wouden, en als je het gebruikt is het totaal onduidelijk of het wel zal werken, maar je loopt wel de kans dat je je eigen hersenen beschadigt. Een rood stoplicht dus. 
http://www.iocob.nl/kanker/kanker-genezen-met-graviola-uit-het-regenwoud-annona-muricata.html

Referenties
[1]: Liaw CC, Chang FR, Lin CY, Chou CJ, Chiu HF, Wu MJ, Wu YC. | New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. | J Nat Prod. | 2002 Apr;65(4):470-5.
[2]: Chang FR, Wu YC. | Novel cytotoxic annonaceous acetogenins from Annona muricata. | J Nat Prod. | 2001 Jul;64(7):925-31.
[3]: Lannuzel A, Höglinger GU, Champy P, Michel PP, Hirsch EC, Ruberg M. | Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae? | J Neural Transm Suppl.| 2006;(70):153-7.
[4]: Champy P, Melot A, Guérineau Eng V, Gleye C, Fall D, Höglinger GU, Ruberg M, Lannuzel A, Laprévote O, Laurens A, Hocquemiller R. | Quantification of acetogenins in Annona muricata linked to atypical parkinsonism in guadeloupe. | Mov Disord. | 2005 Dec;20(12):1629-33.
[5]: Champy P, Höglinger GU, Féger J, Gleye C, Hocquemiller R, Laurens A, Guérineau V, Laprévote O, Medja F, Lombès A, Michel PP, Lannuzel A, Hirsch EC, Ruberg M. | 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.


Graviola and Cancer : a review article describing the exaggerated claims made for the herb graviola in the treatment of cancer.

I don't know who first penned these effusive statements about Graviola  but the claims have taken on a life of their own. I found two dozen  other websites that contained the exact phrasing about Graviola being  "10,000 times stronger than Adriamycin," all equally unsupported by  scientific references. It seems that astounding claims concerning cancer cures spread like a virus from Website to Website.

Since there are now hundreds of sites featuring and selling Graviola, I figured that this herb would also be well represented in PubMed, the  National Library of Medicine's database of peer-reviewed articles.  PubMed contains 12 million citations to nearly all medical journal  articles published since the mid-1960s. But when I entered the term  "Graviola" into this comprehensive search engine all I came up with was  a single item. And this was not a clinical report at all but chemical arcana about screening Brazilian fruits for their aromas.

There had to be something wrong. I went back to the www.graviola.org  website (although exactly whose organization the '.org' refers to is not
apparent) and I clicked on the "clinical references" link at the bottom  of the page. All I got was a blank screen. The same thing with "data  base entries" and "Graviola products." It looked as if someone had  hastily removed some documentary material, but had then forgotten to  remove the links.

I then found a more productive tack. I read that the "active  ingredients" in Graviola are a group of "annonaceous acetogenins" that  are only found in the Annonaceae family, to which Graviola belongs.  "These phytochemicals are being researched around the world for their  active biological properties and potential uses," one website proclaimed.

The phrase "annonaceous acetogenins" gave a new and promising starting  point. Indeed, this term yielded 121 citations in PubMed. A lot of these
were about the chemical constituents of the fruit. But taken  cumulatively, one gathers that there is indeed a class of very  interesting and potentially useful compounds in various branches of the  Annona family. To quote scientists at Purdue University's highly  regarded School of Pharmacy, "Annonaceous acetogenins are an extremely  potent class of compounds, and their inhibition of cell growth can be  selective for cancerous cells and also effective for drug resistant  cancer cells, while exhibiting only minimal toxicity to 'normal'  non-cancerous cells" (Oberlies 1995). Graviola thus joins the list of  hundreds of other biologically active plants that are of potential  importance to the future of medicine.

Further searching in PubMed revealed that it was in fact scientists at  Purdue who had first come up with the widely-circulated "more powerful
than Adriamycin" claim. Here is what Dr. X.X. Liu and colleagues stated  in 1999: "Annoglacins A and B were selectively 1000 and 10,000 times,
respectively, more potent than Adriamycin against the human breast  carcinoma (MCF-7) and pancreatic carcinoma (PACA-2) cell lines in our panel of six human solid tumor cell lines."

This is very exciting in principle. However, to an inquiring, healthily  skeptical mind, several questions immediately suggest themselves. One  is, how much "annoglacin B" is found in a typical Graviola capsule  purchased over the Internet? Quite probably it is infinitessimally  small. Also lost in the promotional hoo-hah is the fact that the  particular annoglacins investigated by Dr Liu and colleagues were  derived not from Graviola at all but from a related, but entirely  different, species, Annona glabra. This is a Polynesian tree called the  pond or alligator apple.

Additionally and most importantly, what do actual clinical studies show  about the effectiveness of this agent against cancer? Back at the www.graviola.org website we read that "three separate research groups  have isolated novel compounds in the seeds and leaves of Graviola which
have demonstrated significant anti-tumorous, anti-cancerous and  selective toxicity against various types of cancer cells, publishing eight clinical studies on their findings."
Really? If we enter the search term Annona into PubMed, but limit our  search with the modifier "clinical trials" (which includes any and all  phases of clinical work), we come up with exactly...zero!  My understanding of the term "clinical studies" is that they necessarily  involve the treatment of human beings (or, more inclusively, pet and  farm animals). Webster says that the term 'clinical' is an observation  that "involves or is based on direct observation of the patient." The  Cancerweb dictionary states that the word 'clinical' pertains to or is  founded on "actual observation and treatment of patients, as
distinguished from theoretical or basic sciences."
But where are these "clinical studies" of Annona derivatives, if they were not to be found among the 12 million peer-reviewed journal articles  of PubMed?

The anonymous authors of the www.graviola.org website seem to have  misspoken. They can't really mean clinical studies. They mean laboratory
experiments that take place in test tubes with cell lines, which many  knowledgeable researchers view as not directly equivalent to human
cancer tissue. (See Gerald B. Dermer's book The Immortal Cell for  corroboration of this point of view.) With this self-serving "slip of  the tongue" the anonymous promoters of Graviola have undoubtedly convinced many cancer patients to buy their product.
Have any of these patients been helped? Or have they been harmed by  unknown or unmentioned side effects? Have they been deprived of precious
time and thereby the opportunity to undergo other, more effective,  treatments? Or have they simply been relieved of unspecified sums of  money? In the vast majority of cases, we'll never know.

Sadly, Graviola has now entered the netherworld of alternative cancer  treatments. It promises much based on real, but very preliminary, scientific facts. Now its reputation has been tarnished by misstatements  and over-promotion. Is there any way for a promising treatment to find  its way back from the Purgatory of Cancer Cure-Alls? Or shall we remain  forever in the dark about the merits of such treatments? Thousands of  cancer patients are waiting for an answer to that riddle.




Oncology (Williston Park). 2008 Sep;22(10):1202.Complementary therapies, herbs, and other OTC agents. Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Graviola demonstrated anticancer effects in vitro, but has not been studied in humans. Despite the lack of human data, many websites promote graviola to cancer patients based on traditional use and on the in vitro studies. Caution is required as there is no evidence of safety or efficacy.



Nutr Cancer. 2011;63(5):795-801. Epub 2011 Jun 22. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Department of Food Science and Technology, Virginia Tech, Blacksburg, Virginia, USA.
The epidermal growth factor receptor (EGFR) is an oncogene frequently overexpressed in breast cancer (BC), and its overexpression has been associated with poor prognosis and drug resistance. EGFR is therefore a rational target for BC therapy development. This study demonstrated that a graviola fruit extract (GFE) significantly downregulated EGFR gene expression and inhibited the growth of BC cells and xenografts. GFE selectively inhibited the growth of EGFR-overexpressing human BC (MDA-MB-468) cells (IC(50) = 4.8 μg/ml) but had no effect on nontumorigenic human breast epithelial cells (MCF-10A). GFE significantly downregulated EGFR mRNA expression, arrested cell cycle in the G0/G1 phase, and induced apoptosis in MDA-MB-468 cells. In the mouse xenograft model, a 5-wk dietary treatment of GFE (200 mg/kg diet) significantly reduced the protein expression of EGFR, p-EGFR, and p-ERK in MDA-MB-468 tumors by 56%, 54%, and 32.5%, respectively. Overall, dietary GFE inhibited tumor growth, as measured by wet weight, by 32% (P < 0.01). These data showed that dietary GFE induced significant growth inhibition of MDA-MB-468 cells in vitro and in vivo through a mechanism involving the EGFR/ERK signaling pathway, suggesting that GFE may have a protective effect for women against EGFR-overexpressing BC.



Int J Mol Sci. 2010 May 6;11(5):2067-78. Antinociceptive and Anti-Inflammatory Activities of the Ethanol Extract of Annona muricata L. Leaves in Animal Models.
Departamento Farmacêutico, Faculdade de Farmácia e Bioquímica, Universidade Federal de Juiz de Fora, Campus Universitário, Martelos, 36036-330, Juiz de Fora, MG, Brazil; E-Mails: glauciemar@gmail.com (G.D.-V.V.); jose.pinho@ufjf.edu.br (J.J.R.G.P.); hytomani@yahoo.com (C.H.Y.).

Antinociceptive and anti-inflammatory activities of the ethanol extract from Annona muricata L. leaves were investigated in animal models. The extract delivered per oral route (p.o.) reduced the number of abdominal contortions by 14.42% (at a dose of 200 mg/kg) and 41.41% (400 mg/kg). Doses of 200 and 400 mg/kg (p.o) inhibited both phases of the time paw licking: first phase (23.67% and 45.02%) and the second phase (30.09% and 50.02%), respectively. The extract (p.o.) increased the reaction time on a hot plate at doses of 200 (30.77% and 37.04%) and 400 mg/kg (82.61% and 96.30%) after 60 and 90 minutes of treatment, respectively. The paw edema was reduced by the ethanol extract (p.o.) at doses of 200 (23.16% and 29.33%) and 400 mg/kg (29.50% and 37.33%) after 3 to 4 h of application of carrageenan, respectively. Doses of 200 and 400 mg/kg (p.o.), administered 4 h before the carrageenan injection, reduced the exudate volume (29.25 and 45.74%) and leukocyte migration (18.19 and 27.95%) significantly. These results suggest that A. muricata can be an active source of substances with antinociceptive and anti-inflammatory activities.

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