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Graviola For Cancer – Are The Claims Valid

 

Graviola For Cancer – Are The Claims Valid?


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Not many are aware of what Graviola is but the benefits of this specific fruit have been hailing a brainstorm in recent times. If you are wondering about the authenticity of the Graviola for cancer, the science does have a lot up its sleeves.

Covering every last detail that there is to know encircling Graviola cancer, we will walk you through everything to clarify all your doubts altogether.

By the end of this article, you will more or less have a fair share of an idea concerning how to use Graviola for cancer treatment and everything that you do need to avoid in this context as well.

What is Graviola?


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Spiky green fruit is what majority of the people tend to refer to Graviola as.

In scientific terms, Graviola is a small evergreen tree which is found in the rainforests of South America, Africa as well as Southeast Asia. This tree is what produces the beneficial heart shapes and spiky fruit which we often use for a number of purposes.

While many might limit its benefits to the realms of just being a sweet treat, the fruit has varying importance in the management of a number of symptoms related to cancer.

The presence of antimicrobial as well as antioxidant properties of Graviola is what had led the researchers to opt for ways to look more into this.

The developing findings regarding this are what are paving way for more and more research in this field. Even though there has been prevailing studies stating the anticancer properties of the Graviola, there have been no concrete clinical studies that prove the benefits of this altogether.

How Does Graviola Cure Cancer?



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It is not surprising for you to be confused about how soursop for cancer treatment is a possibility. It might not necessarily seem like a lot, the same is actually an effective remedy when you come to think of it.

Owing to the budding efficacy of this specific fruit, more and more researchers are delving into this to find the impacts of this fruit in healing cancer.

Graviola has been tested out for its impacts on a varying number of cancers that do tend to have impacts on our day to day life. When it does come down to discussing about the impacts of this specific fruit in the cancer types, let us do take a look at each of them individually.

Let us take a look at each of the type of cancer and see how can graviola cure cancer for good.

1. Breast Cancer


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Majority of the people nowadays do prefer to opt for chemotherapy, if the same is detected at an early stage. Irrespective of the circumstances altogether, there are some breast cancer cells which do become resistant to the normal chemotherapy which is when the Graviola has been tested out for its benefits.

Studies (R) have found that the Graviola extract do have the potential to destroy some of the breast cancer cells effectively, especially the ones that are resistant to a few of the chemotherapy drugs.

Even a conducted study (R) with 19 samples of the Graviola leaf extract from different location did showcase the efficacy of the impact on the breast cancer cell lines of MCF-7, MDA-MB-231, and 4 T1 via the MTT assay.

The researchers found in the result that it is the B1 AMCE which proved out to be a potent candidate for the cancer treatment, especially in the treatment for breast cancer.

2. Pancreatic Cancer



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Pancreatic cancer is yet another one of the variant of cancer that can be cured with the dosage of graviola for cancer.

In a conducted study (R) in 2012, the researchers found the potential benefits of Graviola for cancer. It is not surprising that pancreatic tumours are actually tough to get rid of even with conventional chemotherapies.

The researchers found that Graviola did induce the necrosis of the pancreatic cancer cells by inhibiting the cellular metabolism.

Whatever the circumstances be, it has been found that Graviola for cancer, especially pancreatic cancer has been found to be quite effective for its cure.

All in all, it is believed that the Graviola extract did help manage the metastasis of the pancreatic cancer cells and even inhibited the growth of the cancer cells.

3. Prostate Cancer



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Much like pancreatic cancer and such, it has been found that the usage of Graviola to treat cancer does extend on till for the treatment of prostate cancer as well.

In a few studies that did include experimentation with rats, it was found that Graviola leaves did help in decreasing the size of the prostate effectively in them which further reduced the risks of prostate cancer accordingly.

Yet another conducted study (R) found that the ethyl acetate extract of the Graviola leaves had beneficial impacts in suppressing the risks of prostate cancer in the rats.

4. Colon cancer



ImageSource: www.verywellhealth.com

Graviola leaf extract has been found to have amazing benefits in handling the signs and symptoms associated with colon cancer. It is of no surprise that research has actually shown the efficacy of the Graviola leaf extract in actually helping prevent the induction of the condition associated with colon cancer.

In a conducted study (R) in 2017, it was found that Graviola did have beneficial impacts against colon cancer. They did note that more research needs to be done in this prospect to deduce whether the same does have beneficial anticancer properties or not.

The researchers further did clarify stating that more and more research needs to be done in order to confirm for sure which part of the leaf is the most effective in handling the symptoms related to cancer.

5. Liver cancer



ImageSource: clevelandclinic.org

Yet another one of the cancer types that have been found to have a possible cure with Graviola is liver cancer.

While the prospect of Graviola for cancer is still a matter of hit and miss, it is not necessarily surprising that its efficacy in the treatment for liver cancer is still a matter of concern.

Even studies have claimed and suggested that Graviola extract does have the potential to help in killing some kind of the chemo-resistant cells in the body that the majority of us often tend to complain about.

6. Lung cancer



ImageSource: www.bbc.com

Much like all the predominant types of cancers that we have talked about, even Graviola has been found to have potent benefits in inhibiting the growth of tumours in lung cancer.

Owing to the fact that the lung cancer does impose quite a lot of negative impacts on the body, it is not surprising that Graviola, which has tested out to have beneficial antioxidative and anticancer properties is actually a good enough for the treatment of lung cancer.

How Much Graviola to Take For Cancer?



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If you are here confused about how much Graviola to take for your cancer treatment, the amount is still not medically confirmed or approved.

Clinical trials have still not concurred which is why it is very important to ensure that you consume it once everything is approved and we do get the perfect dosage for the same.

Side Effects Of Graviola Cancer Cure



ImageSource: www.beatcancer.org

Much like the benefits of Graviola for cancer, there are some downsides as well. Side effects are common with this and it is very important to ensure that you keep them in mind while consuming the Graviola to treat cancer.

Studies and tests have revealed that there could be problems, both short term as well as long term.

Some of the long term side effects:

  • Disorders concerning the movement and locomotion
  • Symptoms of myeloneuropathy which further imposes risks of Parkinson’s disease
  • Extended problems associated with liver as well as kidney toxicity

Concluding it all, it is actually quite important to ensure that you consult a doctor if you are opting for Graviola for cancer. It is very important to ensure that you keep the same into consideration to avoid any kind of possible issues concerning your health altogether.

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AFSSA – Referral No. 2008-SA-0171


Maisons-Alfort, April 28, 2010

from the French Food Safety Agency regarding the risks associated with the consumption of soursop and its preparations


1. REFERENCE REMINDER

On June 2, 2008, the French Food Safety Agency (AFSSA) received a request for scientific and technical support from the Directorate General for Health regarding the risks associated with the consumption of soursop (Annona muricata L.) and its preparations.


2. EXPERTISE METHOD

The collective expert assessment was carried out by the Specialized Expert Committee (CES) "Human Nutrition" which met on April 23, 2009, May 28, 2009, June 25, 2009, and July 9, 2009. The following insights can be identified. 3. RATIONALE

Afssa's argument is based on the opinion of the Specialized Expert Committee on Human Nutrition, the elements of which are presented below:

Context

Since 1999, based on observations conducted at the Pointe-à-Pitre University Hospital, a link between the consumption of certain tropical plants and the over-representation of atypical Parkinsonian syndromes has been suggested. The Pointe-à-Pitre University Hospital observed a frequency of around 70% of atypical Parkinsonian syndromes in Guadeloupe compared to 30% for Parkinson's disease, while this ratio is reversed in Europe.

The Pointe-à-Pitre University Hospital specifically studied the hypothesis of the involvement of Annonaceae consumption in this pathology, particularly the consumption of soursop (Annona muricata L.) nectar, juice, and infusions. The AFSSA, in the context of a concerted approach with the AFSSAPS, then suggested conducting animal studies using various traditional preparations of Annona muricata L.

This request for scientific and technical support is based in particular on the work and publications of the Pointe-à-Pitre University Hospital team and on a pharmacy thesis (Champy, 2004b) studying the neurotoxins of Annona muricata L. and their possible implications in the occurrence of atypical Parkinsonian syndromes in Guadeloupe. Three successive periods can be distinguished in the collection and processing of information:

- between 1995 and 2001: observations of clinical cases in Guadeloupe and initial hypotheses proposed by the Pointe-à-Pitre University Hospital team; - between 2001 and 2005: phytochemical and toxicological study of Annona muricata and continuation of epidemiological studies;

Between 2005 and 2009: Study of the mechanisms of action of annonacin and the possible involvement of this compound in atypical Parkinsonian syndromes.

Demonstration of a potential link between atypical Parkinsonian syndromes and the consumption of annonacin.


In 1999, a publication by Caparros-Lefebvre and colleagues highlighted the association between the consumption of tropical plants in Guadeloupe and an abnormally high frequency of atypical Parkinsonian syndromes. Of the 87 cases observed in this publication, 65 patients presented with this type of syndrome. Caparros-Lefebvre and his team (1999) noted that the majority (94%) of patients suffering from PSP, 100% of those with other atypical Parkinsonian syndromes, 60% of controls (people with mild symptoms without neurodegenerative disorders), and those with Parkinson's disease were accustomed to consuming Annonaceae fruits.

The authors then suggested the possible role of Annonaceae in these degenerative disorders.

Annonaceae are plants containing isoquinoline alkaloids, used in the Caribbean in food and traditional medicine, for example:

- Asimina triloba (L.) Dunal (pawpaw);

- Annona squamosa L. or custard apple: leaf infusions are consumed as a purgative and reputed to be aphrodisiacs; - Annona muricata L. (soursop): consumed as fruit and/or leaf teas, considered sedative, sleep-inducing, and relaxing.

Supporting this hypothesis, Lannuzel et al. (2001) showed that the isoquinoline alkaloids of Annona muricata L. can passively diffuse into the intracellular environment and are dopamine transporter inhibitors.

In the absence of precise data on the consumption habits of patients with Parkinson's syndromes, Afssa considers that the responsibility of other causes, both environmental and genetic, cannot be excluded (Angibaud et al. 2004, Caparros et al. 2006, Aubeneau et al. 2008). Botanical information on Annona muricata L.

The soursop, the fruit of the soursop tree Annona muricata, has a dark green skin bristling with soft spines. The interior of the pericarp, granular and creamy, separates into carpels (pseudosyncarpic fruit) with a white flesh rich in juices. A fruit can contain up to 200 seeds (one seed per carpel). The slightly fibrous fruit pulp can be eaten raw; it can be pressed to extract juice or incorporated into sorbets. This pulp can also be fermented in the West Indies, producing a cider-like drink.

While several Annonaceae have uses in traditional medicine, others are known to be toxic and are sometimes used as natural insecticides and fish poisons. Traditional medicine reports the use of soursop leaf teas for sedative and antidiarrheal purposes, and the use of the seeds for pediculicidal and insecticidal purposes. As with most Annonaceae, isoquinoline alkaloids are found in most organs of Annona muricata (leaves, bark, roots, and to a lesser extent in the fruit and seeds).

Chemical characteristics and biological effects of various substances present in Annona muricata L.

Phytochemical and toxicological studies (Champy et al. 2004a, Cha/ 7

DERNS/Enr.22

1- Isoquinoline alkaloids

Quantitative and qualitative estimates have shown that: (i) the alkaloid content of the fruit pulp can reach 0.1%; (ii) that of the nectar is minimal (15 ppm); (iii) the alkaloids present in the leaves increase to 90% in traditional preparations; (iiii) reticuline is the most abundant.

Given that some isoquinolines are inhibitors of complex I of the mitochondrial respiratory chain and of β-ketoglutarate dehydrogenase, as well as disruptors of metabolism and the dopamine transporter. In vitro studies have supported this hypothesis, notably by showing that the isoquinoline alkaloids of Annona muricata L. can passively diffuse into the intracellular environment and are inhibitors of the dopamine transporter (Lannuzel et al., 2001). Isoquinoline alkaloids extracted from the leaves are toxic (apoptotic) to PC12 cells, models of catecholaminergic neurons, and inhibit mitochondrial respiration (Champy, 2004b). While the cytotoxicity of isoquinoline alkaloids has been demonstrated in vitro, in vivo toxicity studies of isoquinoline alkaloids provide conflicting results. The most commonly used method of administration, namely subcutaneous or intraperitoneal injections, is not the most appropriate for testing the hypothesis of toxicity of Annonaceae alkaloids in their traditional and dietary uses (Champy, 2004b).

AFSSA believes that these highly targeted models cannot reflect the conditions of oral exposure of the population.

2- Acetogenins

These are long-chain lipophilic compounds derived from fatty acids (polyacetates derived from the acetate pathway, hence the name "acetogenins"). They are secondary metabolites characteristic of Annonaceae, initially discovered in the seeds, some of which have long been known as insecticides or pesticide. These compounds have the property of inhibiting complex I of the mitochondrial respiratory chain (NADH-ubiquinone oxidoreductase). To date, 400 acetogenins have been identified, and more than 100 A. muricata acetogenins are known (57 in seeds, 34 in leaves, and 28 in roots). Annonacin is relatively abundant in seeds and roots, accounting for 72% of the total acetogenins. An initial study (Lannuzel et al. 2003) was conducted on Wistar rat embryos from which mesencephalic neurons were isolated and cultured. Specific inhibition of mitochondrial complex I activity was demonstrated at a concentration of 100 nM annonacin.
The IC50 is estimated at approximately 30 nM. Damage to dopaminergic neurons is visible at concentrations above 20 nM. A comparison of neuronal toxicity was made with two positive controls: rotenone1 and MPTP2. This 24-hour cytotoxic activity measurement revealed that annonacin is twice as toxic as rotenone (IC50 of 18 nM versus 34 nM) and 100 times more toxic than MPP+, a metabolite of MPTP. In 2007, more specific in vitro/vivo studies were conducted (Escobar-Khondiker, 2007).
It was shown that annonacin induces cell death in striatal neurons as well as an increase and redistribution of tau protein at concentrations between 25 and 100 nM. This redistribution of tau protein results from the inhibition of mitochondrial complex I.
Similar effects on tau protein can be compared to observations of conducted after anatomopathological examinations of Guadeloupean subjects who died from atypical Parkinsonian syndromes (Caparros-Lefebvre et al. 2002). Fragmentation of microtubules, which play a role in the intracellular transport of dopamine vesicles, was also observed.

AFSSA believes that these in vitro data confirm the mechanism of action of annonacin but believes that these highly targeted models cannot be extrapolated to the conditions of exposure in the general population.
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1 plant-derived insecticide
2 1-Methyl-4-phenylpyridinium is used as a reference substance to pharmacologically induce

Parkinson's disease-like pathology in animals.

Various in vivo animal studies have considered the neurological toxicity of annonacin.

The passage of the intestinal barrier by acetogenins (lipophilic) had already been demonstrated (Duret, 1997). Subchronic intoxication tests over 28 days (injections of annonacin into the femoral vein in rats at doses of 1.26 and 7.6 mg/kg/day) were conducted to verify both brain barrier passage and its effects (Champy et al. 2004; Champy, 2004b). Behavior, body mass, spontaneous locomotion, postural instability, adaptation of the forelimbs to forced translation, and the appearance of various organs (heart, lungs, spleen, kidneys, etc.) were not altered.
The main observations included penetration and accumulation of annonacin in the parenchyma, a very significant decrease in ATP in the cerebral cortex, and inhibition of complex I activity of the same intensity (50%) as that exerted by rotenone, with a decrease in oxidative phosphorylation.
Neuronal degeneration of the midbrain dopaminergic areas is also observed. Other brain regions are moderately affected: loss of neurons in the striatal and nigral zones, cytoplasmic and neuronal vacuolation, loss of dopaminergic neurons, a reduction in the number of striatal dopaminergic neurons, and cytoplasmic vacuolation of cholinergic interneurons have been observed (Champy, 2004b).


AFSSA considers that these experimental results demonstrate neurotoxicity of annonacin in vivo. However, the results of the subchronic annonacin poisoning study in an animal model are difficult to extrapolate to humans: the chosen route of administration (intravenous) differs from the human route of exposure, and kinetic data (bioavailability, molecule metabolism) are lacking.

Furthermore, AFSSA considers that the lack of evidence in animals of a dose-response effect and the definition of a no-effect dose makes it very difficult to interpret this neurotoxicity.

Consumption Data

According to quantitative estimates, a consumer of herbal teas, at a rate of one cup per day (2 mg/cup), can ingest 700 mg of total alkaloids in one year, which represents an intake of 10 mg/kg/year. This cumulative intake of total alkaloids (10 mg/kg/year) can also be achieved by a nectar consumer, at a rate of 1 liter per week (Champy, 2004b).


As for annonacin, its concentration in commercial nectar is around 100 mg/liter. It has been shown that acetogenins from the leaves pass into an infusion, without alteration, at a rate of 0.14 mg per cup for crushed leaves (extraction yield of approximately 15%) and 0.4 mg/cup for crushed leaves (extraction yield of approximately 50%). In 2007, a post-hoc dietary survey questionnaire concerning the cumulative consumption of Annona muricata L. (fruits and leaf infusions) over the previous 10 years was administered to 69 sick subjects as well as to 88 non-sick subjects (Lannuzel and al. 2007).

Consumers were classified into two groups: occasional consumers (annual consumption of less than 10 fruits) and heavy consumers (annual consumption of 10 fruits or more). In this publication, the authors estimated that a medium-sized fruit or a glass of fruit juice provides 15 mg of annonacin and a cup of herbal tea 0.14 mg.
Reported consumption was translated into annonacin intake for a body mass of 70 kg and extrapolated based on the duration of the consumption habit. 3 Cumulative lifetime intake was estimated by the authors at 150 g of annonacin in subjects with atypical Parkinsonian syndromes compared to 20-30 g in subjects with Parkinson's disease or healthy controls. Regarding the dietary intake of annonacin presented here, Afssa considers that their estimate, in order to deduce the effects in humans, would merit further refinement through rigorous consumption surveys, taking into account the levels present in the different parts of the plant and in the preparations consumed.

Necessary elements to consider when considering nutritional recommendations

In order to conduct a more precise assessment of the risks associated with the consumption of this type of plant to the population, the following information would be necessary:

- a precise assessment of the levels of annonacin and derivatives present in the plants concerned, as well as relevant data on their level of consumption by the population;

- additional toxicity data on annonacin, including a long-term study (13 weeks by oral administration).

4. CONCLUSION

A link between the consumption of Annonaceae and the overrepresentation of atypical Parkinsonian syndromes in Guadeloupe has been suggested by the Pointe-à-Pitre University Hospital team.

Studies on animal and cellular models have demonstrated proven neurotoxicity of annonacin (acetogenin) and cytotoxicity of the isoquinoline alkaloids present in soursop (Annona muricata L.). However, to date, based on the available experimental data, it is not possible to confirm that the cases of atypical Parkinsonian syndromes observed in Guadeloupe are linked to the consumption of Annonaceae such as Annona muricata L.

Given the current state of knowledge, it is therefore not possible to propose precise quantitative recommendations for soursop consumption in the general population, but soursop-based preparations should be given particular attention due to the risk of extracting toxic compounds.

Given the potential neurological risk of these plant compounds in humans, Afssa believes that research on annonacin is necessary to better characterize the risk associated with soursop consumption, focusing in particular on:
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3

Data collection was carried out over successive 10-year periods. It should be noted that the authors considered that the consumption of 2 fruits/year for 10 years, the consumption of 1 fruit/year for 20 years,

- the kinetic properties of the molecule (oral bioavailability, metabolism, etc.);

- its long-term toxicity in order to assess the risk of consumer exposure to these plant compounds;

- a precise quantification of daily annonacin intake.

AFSSA recommends continuing the epidemiological surveillance of atypical Parkinsonian syndromes in Guadeloupe, which has already been initiated, and implementing, immediately, toxicovigilance monitoring regarding the consumption of soursop and soursop extracts. Executive Director Marc MORTUREUX

KEYWORDS

PARKINSON'S DISEASE, ANNONA MURICATA L., SOURSOP, ANNONACIN, PLANTS


BIBLIOGRAPHICAL REFERENCES:

Angibaud G, Gaultier C, Rascol O (2004) Atypical Parkinsonism and Annonaceae consumption in New Caledonia, Mov Disord 19, 603-4.

Aubeneau L, Bohu PA, Hannequin D, Maltête D (2008) Chronic Parkinsonian Syndrome in a Man Exposed for 10 Years to Insecticide Spraying, Rev Neurol, 164, 374-6.

Caparros-Lefebvre D, Elbaz A (1999) Possible Relationship of Atypical Parkinsonism in the French West Indies with Consumption of Tropical Plants: A Case-Control Study. Caribbean Parkinsonism Study Group, Lancet, 354, 281-6.

Caparros-Lefebvre D, Sergeant N, Lees A, Camuzat A, Daniel S, Lannuzel A, Brice A, Tolosa E, Delacourte A, Duyckaerts C (2002) Guadeloupean parkinsonism: a cluster of progressive supranuclear palsy-like tauopathy, Brain, 1215, 801-11.

Caparros-Lefebvre D, Steele J, Kotake Y, Ohta S (2006) Geographic isolates of atypical Parkinsonism and tauopathy in the tropics: possible synergy of neurotoxins, Mov Disord., 21, 1769-71.

Champy P, Höglinger G U, Féger J, Gleye C, Hocquemiler R, Laurens A, Guérineau V, Laprévote O, Medja F, Lombès A, Michel P, Lannuzel A, Hirsch E C, Ruberg M (2004a) Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical pkinsonism in Guadeloupe, J Neurochem, 88, 63-9.

Champy P (2004b) "Chemical and biological study of neurotoxins from Annona muricata L. (Annonaceae) that may be involved in the occurrence of atypical Parkinsonism in Guadeloupe", Doctoral thesis, University of Paris XI, November 30, 2004.

Duret P (1997) Chemical and biological study of acetogenins from the roots of Annona cherimolla and the seeds of Annona Atemoya (Annonaceae), Doctoral thesis, University of Paris XI, Chatenay Malabry, 1997.

Escobar-Khondiker M, Höllerhage M, Muriel M P, Champy P, Bach A, Depienne C, Respondek G, Yamada E S, Lannuzel A, Yagi A, Yagi T, Hirsch E C, Oertel W, Jacob R, Michel P P, Ruberg M, Höglinger G U (2007) Annonacin, a Natural Mitochondrial complex I Inhibitor, Causes Tau Pathology in cultured Neurons, The J Neurosci, 27, 7827-37.

Hirano A, Malamud N, Kurland LT (1961) Parkinsonism-dementia complex, an endemic disease  on the island of Guam. II: pathological characteristics, Brain, 84, 662-79.

Lannuzel A, Michel PP, Caparros-Lefebvre D, Abaul J, Hocquemiller R, Ruberg M (2001)  Toxicity of Annonaceae for dopaminergic neurons: potential role in atypical parkinsonism in Guadeloupe, Mov Disord, 15 (Suppl.3), 28-35.

Lannuzel A, Michel PP, Höglinger G U, Champy P, Jousset A, Medja F, Lombès A, Darios F, Gleye C, Laurens A, Hocquemiler R, Hirsch E C, Ruberg M (2003) The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism, Neurosciences, 121, 287-96.

Lannuzel A, Höglinger G U, Verhaeghe S, Gire L, Belson S, Escobar-Khondiker M, Poullain P, Oertel W H, Hirsch E C, Dubois B, Ruberg M (2007) Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes? Brain, 130, 816-27.

https://www.anses.fr/en/system/files/NUT2008sa0171.pdf


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Annonaceae acetogenins and atypical Parkinsonism: From annonacin bioavailability to dietary exposure.
Natacha Bonneau







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