 GRAVIOLA,
Hunts Down and Destroys Cancers... Leaving Healthy Cells
Alone.
Graviola, also known as soursop, is a small tree
from the Amazon jungle and some of the Caribbean islands. The
graviola tree (Annona muricata) produces a delicious fruit commonly
called paw-paw, which is widely consumed by indigenous peoples.
What does the research say about Graviola?
There are NO studies or research with graviola done
with humans, or even animals. There are dozens of laboratory tests
done in test tubes. Some of these studies show graviola to have
anti-viral, anti-parasitic and potent anti-cancer properties.
However we do not know if extracts from graviola have the same
effect in humans.
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.
Our Graviola opinion
Until human trials are done, it is difficult to make
any recommendations regarding graviola. However, some of the studies
regarding graviola's anti-cancer potential are intriguing and
certainly worthwhile to further explore.
Our graviola product is 100% pure ground
natural plant material without any binders, fillers, or other
excipients.
Graviola Supplement Facts:
Serving Size 3 Capsules
Servings Per Bottle: 33
Amount Per Serving Graviola - 1.8 g* (Annona
muricata) leaf & stern
Suggested Use: As a dietary supplement, take 1 or 2
graviola capsule 2 times daily or as directed by a health care
professional. Take breaks from use, for instance one week off per
month.
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
) 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. 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.
The fruit and the leaves of Annona muricata (graviola)
are used in traditional medicine for their tranquillizing and
sedative properties. 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. |
