Description: Osage Orange is a deciduous tree which can grow beyond 30 feet. It has a rounded silhouette with the main trunk generally rather short. The
roundness is due to many radiating large branches. The twigs tend to zigzag with leaves that alternate. Leaves are simple, oval affairs with a long stem and sharp, long point. They are smooth edged, a glossy
dark-green on top, a dull light green on the bottom, and have a characteristic milky sap excreted from torn petioles. Leaves tend to be from 3 to 5 inches in length. Some varieties produce thorns, others
don't. The famous fruit, hedge apples, are only produced by female trees. The fruit resembles oranges with brain-like outer skin. The fruit of female trees must be pollinated in order for the fruit to contain
Osage Orange was originally native to a very limited belt starting in Southwestern Arkansas and neighboring Southeastern Oklahoma southward into Eastern Texas
and Northwestern Louisiana. Now through manual commerce and introduction, this tree can be found in almost all sections of the USA. It is a very drought tolerant tree, easily transplanted, and tolerates poor soils,
extreme heat, and occasional subzero cold spells well.
Parts Used: Roots, inner bark, and leaves.
Medicinal Properties: It is said that the Indians utilized a root/water infusion for eye conditions, but not much more seemed to have been done medicinally with this tree from an ethnobotanical point of
view. If the truth be known, I would bet this tree had far more native American applications medicinally than the white man will ever be aware of. The leaves and inner bark will probably offer the most promise for future
medicinal compound extractions—not so much the roots or the fruit. Modern researchers are scrutinizing many of the compounds in the Osage Orange. One of the active compounds is Tetrahydroxystilbene (THS)
which shows significant antifungal activity and probably the one we are most interested in. It is also known as an analog of Resveratrol. That name should ring a bell with most of you! Resveratrol
(3,5,4'-trihydroxy-trans-stibene), a phytoalexin present in grapes, peanuts and pines has antioxidant and anti-inflammatory activities. The TV show, 60 Minutes did a piece on this exciting new compound as featured in wines a
few years ago and set off the craze. However, it should be noted that no one herb or tree is simply one isolated compound! An herb is a sum of its many parts and the Osage Orange tree should be considered in that light. You can
take out of it tetrahydroxystilbene but there are far too many other synergistic compounds to only relegate this tree to just a tetrahydroxystilbene
source. It was found in a study below that tetrahydroxystilbene was not very effective against combating the common fungus, Candida albicans. I guarantee one thing! The Osage Orange is very resistant to Candida infections! So there is much more to this tree than just tetrahydroxystilbene! The Osage Orange is a soup of many anti-microbial chemicals working together to protect this tree in a way that few trees have ever been protected. It is just not about tetrahydroxystilbene, but because so much research has been done on this one compound, we will concentrate on it below.
There are a number of herbalists and alternative health researchers that will tell you that fungi in its many forms is the true general cause of cancer and other chronic diseases. It may
or may not be, but I am sure of one thing, fungi is absolutely underestimated by the medical community in the havoc it can cause in both human and animal pathology. There are few really good, nontoxic antifungals out there for
one to use. Osage Orange is one plant that can bring you a very effective non-toxic, antifungal component. There isn't much out there on the Internet on the value of Osage Orange for medicinal purposes. You will run across some
people using the hedge apple fruit as the main part of the tree to fight cancer, etc. I doubt seriously they are doing themselves justice by concentrating on just the fruit. As with most medicinal trees, the value is not in the
fruit, but found in the leaf or the inner bark of trees. Osage Orange is no different! Almost without exception in the herbal literature, the inner bark (cambium layer and phloem) contains the most powerful concentration of a
plant's chemicals. Compare the Osage to the Olive tree. The olive fruit is unpalatable in its natural state just like the Osage orange ball and both are not the part of the tree generally used in herbal medicine as a remedy. If
you want to experiment with Osage Orange, I urge you to forego the fruit in favor of the leaf or inner bark. If some people are getting that much benefit from just eating the raw fruit, think what the potent leaf or inner bark
will do medicinally! I would suggest either the ethanol extract for oral use or the DMSO extract for topical application in your animals.
There has been quite a bit of research done on
Tetrahydroxystilbene as a tumor inhibitor. Here we find this wonderful analog in the Osage Orange!
Here is an interesting study on Tetrahydroxystilbene as an antifungal:http://www.scienceasia.org/1976.02.n4/v02_202_205.pdf
Other promising antibiotic compounds have been isolated as a non-toxic food preservative from the osage orange. The
subfraction with the greatest inhibitory effect on wood decay fungi as characterized by spectroscopic methods, seems to be a mixture of tetra- & pentahydroxystilbenes. Research is continuing in the laboratory and there is
no reason why we can not do our own veterinary experimenting. Tetrahydroxystilbene may not be the only healing component to this unique tree! Osage Orange extracts should offer a very interesting non-toxic alternative to
combating various infections of a fungal and bacterial nature.
Here is an interesting study on Tetrahydroxystilbene as a tumor inhibitor:http://cancerres.aacrjournals.org/content/61/22/8164.full
And the role of Tetrahydroxystilbene in the treatment of cancer:
A 2001 Abstract:
Resveratrol, a trihydroxystilbene found in grapes and other plants, has been shown to be active in inhibiting multistage carcinogenesis.
Using resveratrol as a prototype, we have synthesized a number of polyhydroxy- and polymethoxy-stilbenes and tested their
anti-proliferative effect in normal and transformed human cells. Here we show that one of the resveratrol analogs, 3,4,5,4'-tetrahydroxystilbene
(R-4), specifically inhibited the growth of SV40 virally transformed WI38 cells (WI38VA) at 10 ¥M, but
had no effect on normal WI38 cells at even higher concentrations. R-4 also prominently induced apoptosis in WI38VA cells, but not in
WI38 cells. RNase protection assay showed that R-4 significantly induced the expression of p53, GADD45 and Bax genes and
concomitantly suppressed the expression of bcl-2 gene in WI38VA, but not in WI38 cells. A large increase in p53 DNA binding activity and
the presence of p53 in the Bax promoter binding complex suggested that p53 was responsible for the Bax gene expression induced by R-4
in transformed cells. Within 4 h of treatment with R-4, the Bax to bcl-2 protein ratio in WI38 and WI38VA cells was, respectively, 0.1 and
105, a difference of three orders of magnitude. While R-4 prominently induced the p53/Bax pro-apoptotic genes, it also concomitantly
suppressed the expression of Cox-2 in WI38VA cells. Taken together, our study suggests that the induction of p53 gene by R-4 in
transformed cells may play a key role in the differential growth inhibition and apoptosis of transformed cells.
A 2008 study on Human Protrate Cancer cells:
Induction of cell cycle arrest in DU145 human prostate cancer cells by the dietary compound piceatannol
Piceatannol (3,4,3',5'-tetrahydroxystilbene) is a naturally occurring polyphenol and analog of the cancer chemopreventive agent resveratrol (3,5,4'-trihydroxystilbene). Piceatannol is
present in the skins of grapes, rhubarb, and sugar cane and is known to have anti-inflammatory and anti-carcinogenic activity. In the present study, we examined piceatannol-mediated regulation
of cell cycle progression in androgen-insensitive DU145 human prostate cancer cells. Cells were treated with 0–10 µM piceatannol. The percentage of cells in G1 phase was increased
in cells treated with piceatannol for 24 h. Piceatannol decreased incorporation of [3H]thymidine into DNA. Piceatannol decreased the protein levels of cyclin A, and cyclin D1. In addition,
cyclin-dependent kinase (CDK)2 and CDK4 protein levels decreased in cell treated with piceatannol. But piceatannol did not affect the expression of the CDK inhibitor p21 or p27. The activity
of CDK2 and CDK4 decreased following piceatannol treatment in a concentration-dependent manner. The present results indicate that piceatannol inhibits the growth of DU145 cell growth by
delaying G1 cell cycle progression, which may be mediated via inhibition of CDK activities.
Some interesting anecdotal cases using the Osage Orange hedgeball for cancer and other afflictions:
Xeno factors are nartural compounds found in plants that possess medicinal properties for animals. Many of them may be classified as
polyphenols. Polyphenol compounds are antioxidants. Many fruits and vegitables contain polyphenols and the Osage Orange has some
unique types and higher levels than most . Polyphenols stimulate and protect the well being of plants and when plants are stressed, they tend
to produce more polyphenols. This is why stressed plants (from drought, infections, etc) contain more polyphenols than unstressed plants.
Animals eating these compounds will also benefit. Resveratrol and all of its analogs are polyphenols.
Oral bioavailability of resveratrol and presumably its analogs (oxyresveratrol, etc) are widely viewed in the literature as being low
because they are rapidly metabolized in the intestines and liver resulting in low blood levels. Hence, they could be a good candidate for liposomal technology
which would allow direct absorption into the blood stream. However, this widely viewed low bioavailability may be
some what misleading. When drugs and food are ingested, they pass into the patient's digestive tract where they are subjected to various
enzymes and digestive juices which will prepare the various compounds to be absorbed into the blood stream and mostly on to the liver.
Some times this results in a compound's efficacy being hurt. The liver will often further process the new absorbed blood compounds
preparing them for the body's cells and will attempt to detoxify others. The polyphenols and particularly the Stilbenes of which reservatrol is
one, will chemically combine with other Xeno factors, sulfur and sugar-like metabolites resulting in low blood levels of free
stilbenes/reservatrol. However, despite these low blood levels, it was found that these new stilbene compounds that were attached to other
Xeno factors stayed in the blood for up to 18 hours from a single dose! It is theorized that despite the low bioavailability of free stilbenes that
the new stilbene metabolites can retain many health benefits in this new form. It is also known that in many pathologies such as cancer and
inflamatory conditons, an enzyme is secreted that will unbind the stilbene metabolites making the free stilbenes available to those cells needing
them. Plus there is often one other overlooked function in which the Xeno factor, quercetin, will inhibit the chemical attachments of sulfur to
the free stilbenes resulting in more free stilbenes in the blood and liver. In short, there is a synergy operating in the Xeno factors that will help
bioabsorbabily far beyond the dosing of only one type. This is not to be ignored and suggests that a broad spectrum source for the Xeno
factors are always the best! This may be why the whole osage orange extract may be of more valuable than just any one isolated compound.
The Osage Orange Heartwood:
Abstract: Analysis of osage orange (Maclura pomifera) heartwood extractives showed that two compounds were present
at much higher levels than previously reported, the flavanonol dihydromorin (2.51%) and the stilbene oxyresveratrol
(2.65%). All compounds present in osage orange heartwood that were tested had low activity against wood-decaying
fungi. The agar plate test showed no synergistic effect, but the soil block test using white-rot fungi suggested synergism. The high durability of osage orange heartwood may be due to the large amounts of oxyresveratrol
and dihydromorin. High levels of one or two monomeric compounds may also explain the exceptionally good durability of black locust and red mulberry heartwood.
The amount of stilbenes that occurs in wine is far less than the amount found in the heartwood of Osage orange, Maclura pomifera. The potential use of Maclura pomifera
in the industry as a medicinal crop may be an advantage due to its growing throughout the region and its
stilbene content of 1.96% in the heartwood. According to some data, in the living organisms oxyveratrol is converted to its isomer with catohol structure.
Abstract: 1,3,6,7-Tetrahydroxyxanthone has been isolated from the heartwood of the osage orange (
Maclura pomifera Raf.). The occurrence in this wood of morin and of 2,3¥,4,5¥-tetrahydroxystilbene has been confirmed.
Abstract: Oxidative stress is one of the major pathological factors in the cascade that leads to cell death in cerebral ischemia.
Here, we investigated the neuroprotective effect of a naturally occurring antioxidant, oxyresveratrol, to reduce brain injury after
cerebral stroke. We used the transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia to induce a defined
brain infarction. Oxyresveratrol was given twice intraperitoneally: immediately after occlusion and at the time of reperfusion.
Oxyresveratrol (10 or 20 mg/kg) significantly reduced the brain infarct volume by approximately 54% and 63%, respectively, when
compared to vehicle-treated MCAO rats. Also, the neurological deficits as assessed by different scoring methods improved in
oxyresveratrol-treated MCAO rats. Histological analysis of apoptotic markers in the ischemic brain area revealed that
oxyresveratrol treatment diminished cytochrome c release and decreased caspase-3 activation in MCAO rats. Also, staining for
apoptotic DNA showed that the number of apoptotic nuclei in ischemic brain was reduced after oxyresveratrol treatment as
compared to the vehicle-treated MCAO rats. This dose-dependent neuroprotective effect of oxyresveratrol in an in vivo stroke
model demonstrates that this drug may prove to be beneficial for a therapeutic strategy to limit brain injury in acute brain ischemia.
THE CONSUMPTION OF NUTRIENTS rich in hydroxystilbenes (resveratrol and oxyresveratrol), such as grapes, red wine, peanuts
and mulberry wood extracts (OSAGE ORANGE), has beneficial effects on human health (8, 9, 56). The cellular and the molecular
mechanisms that underlie these beneficial effects are largely unknown. Several in vitro studies suggest that resveratrol
suppresses the expression of genes involved in the inflammatory response to bacterial and viral stimuli (41, 57). More
specifically, resveratrol or its hydroxylated form, oxyresveratrol (o-RES; trans-2,3',4,5'-tetrahydroxystilbene), reduces the immune
activation of the inducible form of cyclooxygenase (COX-2), a key enzyme in the production of inflammatory prostaglandins (31,
38, 51). Such an effect is likely due to the resveratrol-induced inhibition of the NF-B signaling pathway, a signaling pathway
involved in cox-2 gene expression (26, 30). However, the inflammatory responses in vivo are much more complex than can be
modeled in cultured cells in vitro. As a consequence, there are conflicting data on the in vitro and in vivo effects of resveratrol
(16), most likely because in vivo immune system activation sets in motion complex and intricate inflammatory responses not seen
in vitro. For example, in the best-studied model of innate immune system activation (i.e., a systemic injection of LPS, a component of the outer coat of the gram-negative bac
teria), LPS activates resident macrophages in a variety of tissues (17, 28, 45) to release proinflammatory cytokines such as tumor necrosis factor (TNF)-¥, IL-1, and IL-6, as well as anti-inflammatory cytokines and hormones
with anti-inflammatory activity (12). A variety of transcription factors such as NF-¥B and STAT-3 are consequently activated and lead to
the induction of COX-2 in a variety of tissues in the body, including the brain. One hallmark of innate immune system activation in vivo is fever, an
important component of the host defense response against infection (22). At the molecular level, fever develops as a
result of COX-2 induction in endothelial cells of the brain vasculature followed by a subsequent production of prostaglandin E2
(PGE2) (5, 32). PGE2 induces fever by acting on neurons located within organum vasculosum of the lateral terminalis (OVLT) and
the ventral preoptic region of the hypothalamus (49, 50). In addition to fever, LPS, at higher doses, can also induce hypothermia. It is we
ll established that LPS-induced hypothermia is mediated by the proinflammatory cytokine TNF-¥ (10, 11, 27, 47). Hydroxystilbenes
are available as nonprescription, complementary medications with largely undocumented claims of efficacy. It is important that the actions
of such compounds be subjected to rigorous experimental assessment, so that both the accuracy of claims and the action of
these nonproprietary medications are documented. The LPS fever model provides such an opportunity in light of its
well-understood and characterized actions. Thus one objective of this study was to determine whether o-RES is able to alter LPS
fever via an action on LPS-induced COX-2 in rat OVLT and preoptic area (OVLT/POA). We further explored whether o-RES alters levels of
LPS-stimulated, blood-born inflammatory cytokines, such as TNF-¥ and IL-6 and the level of activation of the transcription factor NF-¥B in the liver, one major target for bacterial LPS (28).
Hydroxystilbenes are naturally occurring polyphenols with protective effects against reactive oxygen and nitrogen species (ROS/RNS).
Here, we investigated oxyresveratrol (OXY), which is contained in high amounts in mulberry wood (osage orange), in comparison to the antioxidant resveratrol (RES).
We found that OXY is a more effective scavenger for 2,2-diphenyl-1-picryl-hydrazyl (DPPH, 100 ¥M) used as a general free radical model, compared to RES or trans-4-hydroxystilbene (IC50
=28.9, 38.5, and 39.6 ¥M, respectively). When primary glial cell cultures were loaded with the ROS/RNS-sensitive fluorochrome 2,7-dichlorodihydrofluorescein, the lowest rise in the fluorescence signal after H2O2
exposure was seen when the cells were pretreated with OXY. Using 4,5-diaminofluorescein
(DAF-2) to monitor free nitric oxide levels (7.7 ¥M NO) in a spectrofluorimetric cell-free assay, we found again that OXY (at 5 ¥M) is a
more effective scavenger. Accordingly, cultures of the murine microglial cell line N9 and primary mixed glial cultures were used to test the
drug effects of NO production upon expression of the inducible isoform of nitric oxide synthase (iNOS). We found that both compounds considerably diminished NO (nitrite) levels, RES more effectively than OXY (IC50
=22.36 and 45.31 ¥M). RES but not OXY down-regulated the expression of iNOS protein, but both did not alter iNOS activity. Furthermore, OXY displayed a generally lower cytotoxicity than RES.
The radical and ROS scavenging properties, as well as the lower cytotoxicity towards microglia and the known good water solubility suggest OXY as a potential protectant against ROS/RNS.
Tyrosinase is responsible for the molting process in insects, undesirable browning of fruits and vegetables, and coloring of skin,
hair, and eyes in animals. To clarify the mechanism of the depigmenting property of hydroxystilbene compounds, inhibitory actions of oxyresveratrol
and its analogs on tyrosinases from mushroom and murine melanoma B-16 have been elucidated in this study. Oxyresveratrol showed potent inhibitory effect with an IC(50) value of 1.2 microm on mushroom tyrosinase activity,
which was 32-fold stronger inhibition than kojic acid, a depigmenting agent used as the cosmetic material with skin-whitening
effect and the medical agent for hyperpigmentation disorders. Hydroxystilbene compounds of resveratrol, 3,5-dihydroxy-4'-methoxystilbene, and rhapontigenin also showed more than 50% inhibition at 100 microm on mushroom
tyrosinase activity, but other methylated or glycosylated hydroxystilbenes of 3,4'-dimethoxy-5-hydroxystilbene,
trimethylresveratrol, piceid, and rhaponticin did not inhibit significantly. None of the hydroxystilbene compounds except
oxyresveratrol exhibited more than 50% inhibition at 100 microm on l-tyrosine oxidation by murine tyrosinase activity;
oxyresveratrol showed an IC(50) value of 52.7 microm on the enzyme activity. The kinetics and mechanism for inhibition of
mushroom tyrosinase exhibited the reversibility of oxyresveratrol as a noncompetitive inhibitor with l-tyrosine as the substrate.
The interaction between oxyresveratrol and tyrosinase exhibited a high affinity reflected in a K(i) value of 3.2-4.2 x 10(-7) m.
Oxyresveratrol did not affect the promoter activity of the tyrosinase gene in murine melanoma B-16 at 10 and 100 microm.
Therefore, the depigmenting effect of oxyresveratrol works through reversible inhibition of tyrosinase activity rather than
suppression of the expression and synthesis of the enzyme. The number and position of hydroxy substituents seem to play an important role in the inhibitory effects of hydroxystilbene compounds on tyrosinase activity.
Abstract: The anti-herpes simplex virus (HSV) compound, oxyresveratrol, purified from a Thai traditional medicinal plant of
Artocarpus lakoocha, was evaluated for its anti-varicella-zoste r virus (VZV) activity. This compound exhibited IC(50) values
(50%-inhibitory concentrations for virus plaque formation) of 12.82, 12.80, 12.99 and 12.82 microg/ml against wild type,
thymidine kinase-deficient and two types of DNA polymerase mutants with acyclovir-resistance , respectively. Thus oxyresveratrol
showed a broad spectrum of anti-VZV activity with a mechanism of action different from that of acyclovir.
(OXY) is a polyhydroxylated stilbene existing in mulberry (osage orange). Increasing lines of evidence have shown
its neuroprotective effects against Alzheimer disease and stroke. However, little is known about its neuroprotective effect in
Parkinson disease (PD). Owing to its antioxidant activity, blood-brain barrier permeativity, and water solubility, we hypothesized
that OXY may exert neuroprotective effects against parkinsonian mimetic 6-hydroxydopamine (6-OHDA) neurotoxicity.
Neuroblastoma SH-SY5Y cells have long been used as dopaminergic neurons in PD research. We found that both pretreatment
and posttreatment with OXY on SH-SY5Y cells significantly reduced the release of lactate dehydrogenase, the activity of
caspase-3, and the generation of intracellular reactive oxygen species triggered by 6-OHDA. Compared to resveratrol, OXY
exhibited a wider effective dosage range. We proved that OXY could penetrate the cell membrane by HPLC analysis of cell
extracts. These results suggest that OXY may act as an intracellular antioxidant to reduce oxidative stress induced by 6-OHDA.
Western blot analysis demonstrated that OXY markedly attenuated 6-OHDA-induced phosphorylation of JNK and c-Jun.
Furthermore, we proved that OXY increased the basal levels of SIRT1, which may disclose new pathways accounting for the
neuroprotective effects of OXY. Taken together, our results suggest OXY, a dietary phenolic compound, as a potential nutritional candidate for protection against neurodegeneration in PD.
Abstract: Hydroxystilbenes are naturally occurring polyphenols with protective effects against reactive oxygen and nitrogen species (ROS/RNS). Here, we investigated oxyresveratrol
(OXY), which is contained in high amounts in mulberry wood, (osage orange) in comparison to the antioxidant resveratrol (RES). We found that OXY is a more effective scavenger for
2,2-diphenyl-1-picryl-hydrazyl (DPPH, 100¥M) used as a general free radical model, compared to RES or trans-4-hydroxystilbene
(IC50=28.9, 38.5, and 39.6¥M, respectively). When primary glial cell cultures were loaded with the ROS/RNS-sensitive
fluorochrome 2,7-dichlorodihydrofluorescein, the lowest rise in the fluorescence signal after H2O2 exposure was seen when the
cells were pretreated with OXY. Using 4,5-diaminofluorescein (DAF-2) to monitor free nitric oxide levels (7.7 ¥M NO) in a
spectrofluorimetric cell-free assay, we found again that OXY (at 5¥M) is a more effective scavenger. Accordingly, cultures of the
murine microglial cell line N9 and primary mixed glial cultures were used to test the drug effects of NO production upon
expression of the inducible isoform of nitric oxide synthase (iNOS). We found that both compounds considerably diminished NO
(nitrite) levels, RES more effectively than OXY (IC50=22.36 and 45.31¥M). RES but not OXY down-regulated the expression of
iNOS protein, but both did not alter iNOS activity. Furthermore, OXY displayed a generally lower cytotoxicity than RES. The radical
and ROS scavenging properties, as well as the lower cytotoxicity towards microglia and the known good water solubility suggest OXY as a potential protectant against ROS/RNS.
The Osage Orange leaf:
Antifungal chalcones from Maclura tinctoria:
The Maclura tinctoria a very close southern relative of our osage orange tree (Maculura pomifera) which has been extensivly studied. Since
the Osage Orange is a close relative and its leaf has never under gone similar analysis like this cousin, this study is worth considering as also applying in all probability to the Osage Orange tree of the USA:
Abstract: Five prenylated flavonoids, including one new natural product, were isolated from an ethanol extract of the leaves of Maclura
tinctoria (L.) Gaud. The new compound has been characterized as 2',4',4,2'-tetrahydroxy-3¥'-[3'?-methylbut-3'?-enyl]chalcone (1). The known compounds were identified as
2',4',4-trihydroxy-3'-[3'?-methylbut-3'?-enyl] chalcone (isobavachalcone) (2), 4,2'-dihydroxy-2'?-[1-hydroxy-1-methylethyl]-2'?,3'?-dihydrofurano[4'?,5'?:3',4'] chalcone (bakuchalcone) (3),
4,4',5'?-trihydroxy-6'?,6'?-dimethyldihydropyrano[2'?,3'?:5',6'?]chalcone (bavachromanol) (4), and 5,7,3',4'-tetrahydroxy-6,8-diprenylisoflavone (6,8-diprenylorobol) (5). All the isolated compounds were evaluated against the
AIDS-related opportunistic fungal pathogens, Candida albicans and Cryptococcus neoformans. Compound 2 was active against both yeasts.
The Osage Orange Fruit:
Anti-inflammatory and antinociceptive potential of Maclura pomifera fruit:
The aqueous, ethanolic and chloroform extracts and two prenylated isoflavones: scandenone (I) and auriculasin (II), isolated
from the fruits of Maclura pomifera (Rafin.) Schneider, were investigated for their in vivo anti-inflammatory and antinociceptive activity. For
the anti-inflammatory activity, both carrageenan-induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear
edema models and for the antinociceptive activity, p-benzoquinone-induced abdominal constriction test were used. Scandenone, the
chloroform and the ethanolic extracts were shown to possess antinociceptive activity and anti-inflammatory activity on carrageenan-induced
hind paw edema model at 100 mg/kg dose. The same compound and the extract were also found to be highly active in (TPA)-induced
mouse ear edema model whereas auriculasin and the H2O extract showed to be inactive in all of the assays.
Flavonoids and isoflavonoids are well known for their beneficial effects on human health and their anti-insect and anti-microbial
activities in plants. Osage orange fruit is rich in prenylated isoflavones and dihydrokaempferol and its glucoside. Four glycosyltransferases
were identified from a collection of osage orange fruit expressed sequence tags. Biochemical characterization suggested that the
glycosyltransferase UGT75L4 might be responsible for glucosylation of dihydrokaempferol in vivo, although this enzyme exhibited broad
substrate recognition toward isoflavonoids and flavonoids in vitro. UGT88A4 was active on coumarin substrates. Identification of highly
active phenylpropanoid glycosyltransferases will facilitate the metabolic engineering of glycosylated natural products in plants.
The major constituents of fruits of Maclura pomifera are the prenylated isoflavones, osajin (1) and pomiferin (2). Since
significant biological activities of extracts from the wood of M. pomifera were previously reported, the peroxynitrite scavenging activity,
inhibition of lipid peroxidation, scavenging of DPPH and EROD activity of these two major substances were studied.
This study investigated the isoflavone content in a unique nonedible tree fruit, Osage orange [Maclura pomifera (Raf.) Schneid],
and methods for the extraction, identification, and quantification of the two major isoflavones, osajin and pomiferin, were developed. The
ethyl acetate extract contained 25.7% osajin and 36.2% pomiferin, and the two isoflavones were at 9.5 g kg-1 of fresh Osage orange. Two
model systems, FRAP and ¥-CLAMS, were used to measure the antioxidant activity of these two isoflavones. Pomiferin was found to be a
strong antioxidant in both systems, comparable to the antioxidant vitamins C and E and the synthetic antioxidant BHT. Osajin and the two
soybean isoflavones (genistein and daidzein) showed no antioxidant activity. Although the Osage orange fruit is not a food source, it is
considered to be safe and, therefore, a potentially good source of an antioxidant nutraceutical and functional food ingredient.
Abstract: A reinvestigation of the constituents of the Osage orange (Maclura pomifera
) yielded, in addition to the previously reported triterpenes (lupeol, butyrospermol, and lupane-3¥,20-diol), the pigments osajin and pomiferin, and a previously unreported constituent. The
structure of this new compound was investigated. On the basis of spectroscopic and chemical data, it appeared to be an epimer of lupeol and is referred to as 19-H-lupeol.
Lupeol as found in the osage orange has been shown of value in Pancreatic Cancer:
Abstract: Pancreatic cancer is an exceptionally aggressive disease, the treatment of which has largely been unsuccessful due to higher
resistance offered by pancreatic cancer cells to conventional approaches such as surgery, radiation and/or chemotherapy. The aberration of
Ras oncoprotein has been linked to the induction of multiple signaling pathways and to the resistance offered by pancreatic cancer cells to
apoptosis. Therefore, there is a need for development of new and effective chemotherapeutic agents which can target multiple pathways to
induce responsiveness of pancreatic cancer cells to death signals. In this study, human pancreatic adenocarcinoma cells AsPC-1 were used to investigate the effect of Lupeol
on cell growth and its effects on the modulation of multiple Ras-induced signaling pathways. Lupeol
caused a dose-dependent inhibition of cell growth as assessed by MTT assay and induction of apoptosis as assessed by flow cytometry,
fluorescence microscopy and western blotting. Lupeol treatment to cells was found to significantly reduce the expression of Ras oncoprotein
and modulate the protein expression of various signaling molecules involved in PKC¥a/ODC, PI3K/Akt and MAPKs pathways along with a
significant reduction in the activation of NF¥?B signaling pathway. Our data suggest that Lupeol can adopt a multi-prong strategy to target
multiple signaling pathways leading to induction of apoptosis and inhibition of growth of pancreatic cancer cells. Lupeol could be a potential
agent against pancreatic cancer, however, further in-depth in vivo studies are warranted.
Researchers induced head and neck cancer in mice and then gave the mice doses of the chemical lupeol, a triterpene compound found in
many fruits. The lupeol appeared to block the function of a protein called NFkB, which assists both healthy and malignant cells in the
process of growth and repair. In addition, the growth and spread of the cancer appeared to be slowed. From the animal models, not only
did lupeol suppress the spread, the tumor got smaller. Compared to conventional drugs, lupeol reduced the size of the tumor far faster," researcher Terence Lee said.
In prostate cancer, a fine balance between cell proliferation and apoptotic death is lost, resulting in increased cellular mass and
tumor progression. One approach to redress this imbalance and control this malignancy is its preventive intervention through the use of
dietary natural agents. Here, we investigated the growth-inhibitory effect and associated mechanisms of Lupeol, a triterpene present in fruits
and vegetables, in androgen-sensitive human prostate cancer cells. Lupeol treatment resulted in significant inhibition of cell viability in a
dose-dependent manner and caused apoptotic death of prostate cancer cells. Lupeol was found to induce the cleavage of poly(ADP-ribose)
polymerase protein and degradation of acinus protein with a significant increase in the expression of FADD protein. Among all death
receptor targets examined, Lupeol specifically caused a significant increase in the expression of Fas receptor. The small interfering
RNA-mediated silencing of the Fas gene and inhibition of caspase-6, caspase-8, and caspase-9 by their specific inhibitors confirmed that
Lupeol specifically activates the Fas receptor-mediated apoptotic pathway in androgen-sensitive prostate cancer cells. The treatment of cells
with a combination of anti-Fas monoclonal antibody and Lupeol resulted in higher cell death compared with the additive effect of the two compounds alone, suggesting a synergistic effect. Lupeol
treatment resulted in a significant inhibition in growth of tumors with concomitant reduction in prostate-specific antigen secretion in athymic nude mice implanted with CWR22Rnu1 cells. Because early clinical prostate
cancer growth is an androgen-dependent response, the results of the present study suggest that Lupeol may have a potential to be an effective agent against prostate cancer.
"Isoflavones from both soy and Osage orange recently have been demonstrated by other laboratories to protect brain cells, or neurons,
from the toxic effect of amyloid beta peptide. Amyloid beta peptide is believed to be responsible for the degeneration of neurons in
Alzheimer's patients. However, the precise mechanisms by which isoflavones block the toxicity of amyloid beta peptide are unknown.
Soybeans contain less than one-tenth of one percent isoflavone compounds, Whaley said. By comparison, between 5 percent and 10
percent of the dry mass of a bois d'arc apple is composed of isoflavone compounds. This plant has somehow developed the ability to
produce extraordinary high levels of isoflavone compounds," Whaley said. "There is no known dietary plant that contains this high level of
isoflavones.Whaley's research is focused on determining the molecular structure of the unique kind of isoflavones found in the Osage orange
and on identifying the enzymes, and the genes that encode them, that are responsible for producing these compounds. Once the genes are
identified and cloned, it may be possible to insert these genes into other, more palatable dietary plants, or forage plants eaten by livestock, he
said.There are different kinds of isoflavones, each with their own unique structure," Whaley said. "The ones in the Osage orange have a
peculiar structure that makes them very water insoluble. But they could be used as precursors in the chemical synthesis of other ingestible
isoflavones.Whaley is particularly interested in how isoflavones protect brain cells from the toxic effects of the amyloid beta protein, which
travels through the blood stream by hitching a ride within low-density lipoprotein, or LDL, particles. Whaley's recent research has focused
on how isoflavones get inside, or partition into, lipid structures called micelles. These micelles are simple lipid structures that are chemically
similar to LDL particles. To study the mechanisms for how isoflavones get inside the LDL particles in the body, Whaley has used micelles as
a simple model. He adds a special detergent to water that forms micelles, and by adding isoflavones to the mix, he can then observe how the
isoflavones position and orient themselves within the micelle structure. The position and orientation of isoflavones is a key consideration in
understanding how they protect lipid structures from reactive oxygen species, which are also called free radicals. It is the reactivity of free
radicals that ultimately is responsible for the aging process. "The next step is to take the techniques we've developed for studying detergent
micelles and translate those techniques into more complex models and eventually into cells," he said. "The mechanism by which isoflavones
block neurotoxicity could be related to their ability to lodge into lipid membranes, because that is where the precursor to amyloid beta
peptide is usually located. Understanding the basic structure of the isoflavones and their interaction with lipid structures hopefully will give us
insight into how natural chemicals in fruits and vegetables may lower the risk for developing diseases such as Alzheimer's disease or
atherosclerosis. "Coming up with a magic bullet to treat Alzheimer's disease is a long way off, but I think there's a chance of learning
something through natural products such as the isoflavones produced by Osage orange. They probably will not provide an immediate drug,
but understanding their biological activities may indicate an avenue of research for developing a new pharmaceutical."
Abstract: The fruit of the osage orange tree (Maclua pomifera
[Raf.] Schneider) was shown to contain at least four pigments with antioxidant activity. Pomiferin was present as 3 to 4% of the dry fruit and, as a primary antioxidant, was responsible for 20–25% of the
activity exhibited by methanol extracts. An unidentified substance was also present which reacted synergistically with pomiferin, increasing its
contribution to the overall activity to approximately 75%. The three new pigments, totalling 0.5% to .75% of the dry fruit, all showed
antioxidant activity exceeding that of pomiferin when tested at equal concentrations. A chromatographic procedure, employing anhydrous
magnesium sulfate, was developed and applied successfully in separating mixtures of several iso-flavone pigments.
In Osage orange, osajin and
pomiferin account for between 5 and 10 percent of the dry mass of the fruit tissue. This is an extraordinary
amount of isoflavone and is much higher than the isoflavone content of soybean (approximately 0.1% by mass). Osajin and pomiferin were
first isolated and characterized by researchers at The Ohio State University in the late 1930s. It appears from this study that a 90/10, v/v, methanol/water solvent was used to extract these isoflavones. O
sajin and pomiferin have low solubility in solvent mixtures containing small amounts of water.
The objective of the present 15-day study was to evaluate the cardioprotective potential of flavonoid pomiferin isolated from the infructences of Maclura pomifera
, Moraceae, against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based
composite therapy. Studies were performed with isolated, modifi ed Langendorff-perfused rat hearts and ischemia of heart was initiated by stopping the coronary flow for 30 min, followed by 60 min of reperfusion (14 ml min-1
). Wistar rats were divided into three groups. The treated group received pomiferin (5 mg/kg/day in 0.5% Avicel); the placebo group received only 0.5% Avicel; the intact group was left
without any applications. Biochemical indicators of oxidative damage, lipid peroxidation product malondialdehyde, antioxidant enzymes
(superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and myocardium has been evaluated. We also examined the
effect of pomiferin on cardiac function (left ventricular end-diastolic pressure, left ventricular pressure, peak positive +dP/dt (rate of pressure
development) after ischemia and reperfusion. Our results demonstrate that pomiferin attenuates the myocardial dysfunction provoked by
ischemiareperfusion. This was confirmed by the increase in both the antioxidant enzyme values and the total antioxidant activity. The
cardio-protection provided by pomiferin treatment results from the suppression of oxidative stress and correlates with the improved ventricular function.
Abstract: Recent findings that many human chronic diseases are associated with oxidative stresses have instigated the search for dietary
antioxidants. Many phytochemicals, particularly phenolic compounds, have been found to possess strong antioxidant activity and reduce the
risks of those diseases. Isoflavones, a special phenolic group found in soybean, have been found to act as antioxidants in some model
systems. This study investigated the isoflavone content in a unique nonedible tree fruit, Osage orange [Maclura pomifera (Raf.) Schneid], and
methods for the extraction, identification, and quantification of the two major isoflavones, osajin and pomiferin, were developed. The ethyl
acetate extract contained 25.7% osajin and 36.2% pomiferin, and the two isoflavones were at 9.5 g kg(-1) of fresh Osage orange. Two
model systems, FRAP and beta-CLAMS, were used to measure the antioxidant activity of these two isoflavones. Pomiferin was found to be
a strong antioxidant in both systems, comparable to the antioxidant vitamins C and E and the synthetic antioxidant BHT. Osajin and the two
soybean isoflavones (genistein and daidzein) showed no antioxidant activity. Although the Osage orange fruit is not a food source, it is
considered to be safe and, therefore, a potentially good source of an antioxidant nutraceutical and functional food ingredient.
Estimated Solubility of
Water—0.640 mg/ml, 0.03 g/L
Ethanol—328 mg/ml, 50g/L
are practically insoluble in water. Flavones are poorly water soluble. Flavonoids are water soluble polyphenolic molecules
containing 15 carbon atoms. Phenolic compounds can be efficiently extracted from legumes using an ethanol/water (70:30 v:v).
is a fat-soluble compound and soluble in ethanol at 50 mg/ml, in DMSO at 16 mg/ml at least, and is only very slightly soluble in water at ~3 mg/100 ml. Resveratrol exists as two structural isomers: cis- (Z) and
trans- (E). Both cis- and trans-resveratrol are glucosides, which mean they bound to a glucose molecule. When exposed to heat or ultraviolet radiation, the trans- form can undergo
isomerisation to the cis- form. Resveratrol occurs predominantly in the trans- form, which is the more stable form of resveratrol. It was found
to be stable at 75% humidity and 40¥C in the presence of air, all of which are conditions of "accelerated stability." Trans-resveratrol is more biologically active and more commonly studied compared to the cis- form.
Ultrasonic extraction is considered one of the simplest extraction techniques because it is easy to perform with common laboratory
equipment (i.e. ultrasonic bath). In this method, the crushed sample is mixed with the suitable solvent and placed into the ultrasonic bath
where the working temperature and extraction time are set. Ultrasound can enhance existing extraction processes and enable new
commercial extraction opportunities and processes. The main targets have been polyphenols and carotenoids and in both aqueous and
solvent extraction systems. The ultrasound extraction trials have demonstrated improvements in extraction yield ranging from 6 to 35%
"In general, ultrasound can lead to a permeabilization of cell membranes to ions (Mummery 1978), and it can reduce the
selectivity of the cell membranes significantly. The mechanical activity of the ultrasound supports the diffusion of solvents into the
tissue. As ultrasound breaks the cell wall mechanically by the cavitation shear forces, it facilitates the transfer from the cell into
the solvent. The particle size reduction by the ultrasonic cavitation increases the surface area in contact between the solid and the liquid phase.".
The extraction of resveratrol (should also hold true for oxyresveratrol) via ultrasonic extraction may offer the best and shortest
extraction times. Liushu Xing using ultrasonic extraction for resveratrol in the plant, Polygonum cuspidatum, determined the optimum
process conditions: ultrasonic power 250W, pH 4.0, solid-liquid ratio 1:20, temperature 40 degrees , ultrasonic time of 30 min, 80 %
ethanol and 80% acetone (1:1), resulting in a resveratrol extraction rate of 3.34%. Other study results show that the ultrasonic extraction
which brings the best results. The optimum extraction conditions were: 15 times, 75% ethanol, ultrasonic extraction for 60 min, resveratrol
extraction rate of 0.03 mg / g. This method is a simple technique can increase the extraction efficiency and shorten the extraction time,
low-temperature conditions, with ultrasonic extraction is also beneficial to the maintenance of the active ingredients of the original drug in the nature of the active ingredients.
Air is being pumped out of a mason jar containing Osage Orange heartwood.in a 80% ethanol/water menstruum. This process aids in the
efficiency of producing a herbal tincture by removing the air bubbles in the marc resulting in the menstruum being drawn more intimately into contact of the plant material.
The osage orange heartwood macerate in vacuumed jar is next placed in an ultrasonic bath to sonicate the tincture. This avoids the high heats
of many other traditional extraction processes in favor of this ultrasonic low heat, high energy method. It produces a far superior quality of
tincture. I allow this tincture to macerate for 30 days, routinely sonicating the jar every few days in 20 minute cycles.
I had origninally concluded that the Osage Orange fruit was probably of debatable medicinal value when compared to the inner bark and
leaf. However, I can see as you can from the above research that the fruit may offer some unique compounds not found in other parts of this
tree. Neverheless, I have to conclude that this tree's inner bark probably will offer the best source for the complete "soup" of all the
medicinal compounds that this tree has to offer. After all, the inner bark is the pathway by which the leaf, the fruit and the heartwood obtains
their unique components and it is the inner bark that has long been esteemed in herbal medicine as the most valuable part of any medicinal
tree. The leaf and the fruits are the easiest components to obtain for medicine making. The heartwood, less so and the inner bark probably
the most time consuming of all to collect. Prices for Osage Orange tincture will reflect this. You will pay higher prices for the inner bark and heartwood tincture as compared to the fruit and leaf tinctures.
Osage Orange Leaf tincture will likely contain five valuable flavonoids and anti-fungal extracts similar to its close relative, Maclura
tinctoria. Its leaf should be of use as a cheap safe means of fighting fungal infections.
2) Osage Orange Heartwood tincture contains the stilbenes, Oxyresveratrol & Tetrahydroxystilbene
(THS), plus the the flavanonol, dihydromorin and like the leaf should be invaluable in fighting fungal infections, has antiviral potential, neuroprotective effects, plus as a
general immune stimulant. It appears that oxyresveratrol may be more desirable on several counts than the highly touted resveratrol!
3) Osage Orange fruit tincture has been shown to contain the isoflavones:
scandenone, osajin, pomiferin and auriculasin, along with the triterpenes lupeol, butyrospermol, and lupane-3B,20-diol. Lupeol has been linked to induction of apoptosis and inhibition of
growth of pancreatic and prostate cancer cells. One would surmise this tincture would be of value as an anti-microbial, anit-tumor and anti-cancer medicinal along with a cell and cardio protectorate .
4) Osage Orange inner bark tincture should traditionally prove to have the best combination of all of the previoiusly described
phytochemicals in one tincture. Almost without exception in the herbal literature, the inner bark (cambium layer and phloem) contains
the most powerful concentration of a plant's chemicals and is the primary location harvested in creating a medicinal extract.
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