[Heavy_Lifter85]

Abstract
Background: Plants containing compounds such as the isoflavonoids, with female hormone-like
effects that bind to human estrogen receptors, are known. But none has been previously shown to
have corresponding male hormone-like effects that interact with the human androgen receptor.
Here, we report that the tree bark (cortex) of the Gutta-Percha tree Eucommia ulmoides possesses
bimodal phytoandrogenic and hormone potentiating effects by lipidic components.

Methods: The extracts of E. ulmoides were tested using in-vitro reporter gene bioassays and in-vivo
animal studies. Key compounds responsible for the steroidogenic effects were isolated and
identified using solid phase extraction (SPE), high performance liquid chromatography (HPLC), thin
layer chromatography (TLC), gas chromatography-mass spectroscopy (GC-MS), electron spray
ionisation-mass spectroscopy (ESI-MS) and nuclear magnetic resonance (NMR).

Results: The following bioactivities of E. ulmoides were found: (1) a phenomenal tripartite
synergism exists between the sex steroid receptors (androgen and estrogen receptors), their
cognate steroidal ligands and lipidic augmenters isolated from E. ulmoides, (2) phytoandrogenic
activity of E. ulmoides was mediated by plant triterpenoids binding cognately to the androgen
receptor (AR) ligand binding domain.

Conclusion: In addition to well-known phytoestrogens, the existence of phytoandrogens is
reported in this study. Furthermore, a form of tripartite synergism between sex steroid receptors,
sex hormones and plant-derived lipids is described for the first time. This could have contrasting
clinical applications for hypogonadal- and hyperlipidaemic-related disorders.

Attached File(s)

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[Jakeshorts]

not so novel heavy. I've been trying to get people hyped about this shit for a while have a look:

http://www.mindandmuscle.net/forum/index.php?showtopic=31868

it's a chinese herb called du zhong. It's terribly expensive. Make sure you get the cortex extract though. I little pricey with shipping for my taste and an experiment.

[lordshockspeare]

[quote name='Jakeshorts' date='Jan 29 2008, 06:59 PM' post='452921'
it's a chinese herb called du zhong. It's terribly expensive. Make sure you get the cortex extract though. I little pricey with shipping for my taste and an experiment.
[/quote]

What is thecortex extract?
I found source for the bark extract on:
Bulk Herbs
It does seem like a rather expensive experiment to see if it truly has positive effects though.

[Jakeshorts]

I've looked at several different sites' products and all I know is some times it says it specifically and other times it doesn't I know that in the study i based my thread off of they used the "cortex" extract. I lost interest as it wasn't generating any conversation and gave up research when I found out the price was a little more salty than what i wanted to experiment with.

[Heavy_Lifter85]

not so novel heavy. I've been trying to get people hyped about this shit for a while have a look:

Me too; from 4-27-2007: http://forum.bodybuilding.com/showthread.p...71#post37502371

Anyway, PA weighed in: "this is a very intriguing study. However what concerns me is that they looked only at activity and testosterone potentiation on the prostate. the prostate has very unique behaviour towards hormones so the possibility exists that this stuff has specific activity there and not elsewhere in the body (which would not be good)."

[Jakeshorts]

nice post. Always good to here what PA says about androgens. Wish he stopped by here more often.

This "might" would need to be tested. but damn... I just can't shell out the clams. Are you planning on running this soon?

[methodice]

Here you go boys: MAN Primal Male

Serving Size: 6 MAN Caps

Dosed: 3 caps, 2 times daily

Fadogia aggrestris........................1500mg
Eucommia ulmoides.......................1200mg
Epimedium (SE - 20% Icariin)...........450mg
I3C.............................................300mg
Zinc Orotate..................................30mg
Copper Orotate................................3mg
Vitamin B6 (pyridoxine HCl)................10mg

[Heavy_Lifter85]

Gather the MAN stuff is $28 for 20 days worth of product. Still, I'll wait for the reviews at bb.com. Disposable income is not what it used to be.

[Lost Metal]

Here you go boys: MAN Primal Male

Serving Size: 6 MAN Caps

Dosed: 3 caps, 2 times daily

Fadogia aggrestris........................1500mg
Eucommia ulmoides.......................1200mg
Epimedium (SE - 20% Icariin)...........450mg
I3C.............................................300mg
Zinc Orotate..................................30mg
Copper Orotate................................3mg
Vitamin B6 (pyridoxine HCl)................10mg

Looks solid.

Unfortunately (not 100% sure) I don't think theres
any definitive research about the anabolic activity.

Could be this stuff is great for growing facial hair and thats it.

[Odium]

Do we have any reason to believe that phyto-androgens will not suffer the same fate as most androgens in the liver?

[Heavy_Lifter85]

I would refer to the structure of euphol on page seven of the attached paper and the steroid template at http://www.chem.qmul.ac.uk/iupac/steroid/3S01.html when reading this post. Also, a keto group is C=O ; a hydroxyl group is C-OH. Saturated/saturation means you have/produce a double bond; reduction/reduced means you are making or have a single bond.
------------------------------------------------------------------------------------------------------
My thought is no, but it will depend to a large extent on how much "give" there is in ligand binding to the cytochromes P-450. There are five processes which serve to inactivate steroids, but based on the structure of euphol, only some of these apply.

Reduction of the keto group at C-3 to a hydroxyl group is certainly a concern, but every oral androgen is subject to this effect, and they seem to overcome it. 3-beta-hydroxysteroid dehydrogenase could reform the keto group and unsaturated the C-3 to C-4 bond. But C-3 is hindered by the dual methyl groups at C-4 anyway, so all this may be moot.

We don't have a C-20 keto group, so no worries here.

Oxidation of 17-beta-hydroxyl group does not seem to be a concern, as euphol has a long carbon chain at C-17. Something along the lines of cholesterol side chain cleavage and 17,20-lyase could remove this, but it's a long shot.

A hydroxyl group can be introduced at C-7 of 5-alpha reduced androgens (i.e. "DHT derivatives"). Euphol is 5-alpha reduced, but binding again comes into play.

Conjugation of sulphate groups and glucuronide groups would deactivate euphol and allow excretion. This requires a hydroxyl group, generally at C-3. Again, euphol starts with a keto group there and C-4 is hindered.

Anyone is familiar with the metabolism or bioavailability of ecdysterone, turkesterone, etc.? Or wait for someone on bb.com to log it .

[Heavy_Lifter85]

Where's PA when you need him?

[Jakeshorts]

I would refer to the structure of euphol on page seven of the attached paper and the steroid template at http://www.chem.qmul.ac.uk/iupac/steroid/3S01.html when reading this post. Also, a keto group is C=O ; a hydroxyl group is C-OH. Saturated/saturation means you have/produce a double bond; reduction/reduced means you are making or have a single bond.
------------------------------------------------------------------------------------------------------
My thought is no, but it will depend to a large extent on how much "give" there is in ligand binding to the cytochromes P-450. There are five processes which serve to inactivate steroids, but based on the structure of euphol, only some of these apply.

Reduction of the keto group at C-3 to a hydroxyl group is certainly a concern, but every oral androgen is subject to this effect, and they seem to overcome it. 3-beta-hydroxysteroid dehydrogenase could reform the keto group and unsaturated the C-3 to C-4 bond. But C-3 is hindered by the dual methyl groups at C-4 anyway, so all this may be moot.

We don't have a C-20 keto group, so no worries here.

Oxidation of 17-beta-hydroxyl group does not seem to be a concern, as euphol has a long carbon chain at C-17. Something along the lines of cholesterol side chain cleavage and 17,20-lyase could remove this, but it's a long shot.

A hydroxyl group can be introduced at C-7 of 5-alpha reduced androgens (i.e. "DHT derivatives"). Euphol is 5-alpha reduced, but binding again comes into play.

Conjugation of sulphate groups and glucuronide groups would deactivate euphol and allow excretion. This requires a hydroxyl group, generally at C-3. Again, euphol starts with a keto group there and C-4 is hindered.

Anyone is familiar with the metabolism or bioavailability of ecdysterone, turkesterone, etc.? Or wait for someone on bb.com to log it .

read the turketerone thread in CNW subforum. I did some research on it - human don't have an ecdysterone receptor. Insects do. Turkesterone is classified as an ecdysterone, but turkesterone was found to have a hydroxyl group. So your pet ant would benefit greatly from supplementing with either.

EDIT: although a pubmed search found a study posted in the thread listed above showing increased anabolism from turk. in the same sense that Synthesize does, but I highly doubt the MOA is related.

[Heavy_Lifter85]

read the turketerone thread in CNW subforum. I did some research on it - human don't have an ecdysterone receptor. Insects do. Turkesterone is classified as an ecdysterone, but turkesterone was found to have a hydroxyl group. So your pet ant would benefit greatly from supplementing with either.

No shit. That's not why I was asking - there may be some similarity between the action of P-450 on ecdy/turk and euphol.

[Heavy_Lifter85]

I wouldn't expect turk/ecdy/euphol to have any degree of affinity for the AR, based on structure alone. Again, the interesting point is the "tripartite synergism between sex steroid receptors, sex hormones and plant-derived lipids" showing action past the point of saturation at the AR.

[Jakeshorts]

No shit. That's not why I was asking - there may be some similarity between the action of P-450 on ecdy/turk and euphol.

the question was about bioavailability. The answer fits. Don't be phallus.

Not to mention I've started a thread with the fucking same exact title in december I think. I suggest you do a search.

[Heavy_Lifter85]

Ok, found and read it. There's not much beyond the posting of abstracts. The crux of the matter, that phytoandrogens act as cofactors, is raised by Kimbo:

"One angle to consider: Flax was often used as a gynecomastia preventative/reverser. One explanation for its mechanism of action is that the phytoestrogens in flax attach to estrogen receptors, effectively reducing the effect of estrogen. I wonder if it's possible that a phytoandrogen might work in a similar manner - in which case it wouldn't be desirable. "

but then never really discussed. It's obvious from the authors' conclusion that exactly the opposite of what Kimbo describes occurs between euphol and the AR (that's why they call it "tripartite synergism").

Previous to reading Kimbo's statement, I was under the impression that euphol binded the AR. (I think Jake believed the same about phytoandrogens, i.e. "human don't have an ecdysterone receptor") Euphol AR binding now appears to be incorrect. A conventional steroid binds the AR and euphol acts as a cofactor or prosthetic group (I'm not using the term in the strict sense) and enhances the binding or the response caused by the ligand-receptor complex. The action of euphol would be somewhat analogous to hemoglobin binding one O2, then having greater affinity for another O2, or some of the proteins involved in DNA manipulation increasing the speed and fidelity of the process.

Anyone one more about cofactors or prosthetic groups?

I would still like to see information about ecdy/turk metabolism in the liver, as this might relate to euphol oral bioavailability.

[Jakeshorts]

What's euphol's significance to ecdysterones? Admittedly some of this is over my head, I'll do research and catch up when I have the time - in the meanwhile - i didn't discuss kimbo's accertation as he didn't provide anything other than a "what if". All I was going on was the study's results - which is in regards to du zong, NOT ecdy... So I'm not sure why your grouping the two together. No studies on ecdy that I've seen show any involvement of the trifecta you decribed above.

Is euphol a pphytoandrogen? Or are you suggesting ingesting euphol in addition to phytoadrogens is somehow going to increase their bioavailability? The problem with phytoandrens is the same with phyto estrogens - though some act differently than others they're all called the same thing. It's cutting edge science with behind the times nomenclature.

The flaw here lies in your addition of ecdysterone. I think you'd have better luck using the du zong.

[Heavy_Lifter85]

What's euphol's significance to ecdysterones?

There might (big might) be some similarity in the action of P-450 on the C-17 side chain. I'm just wondering about the oral bioavailability of euphol and looking for something to compare it to. This is the reason I group ecdy with euphol. Ecdy might also act in the same manner as euphol; I'm not saying it does since I have no information on the subject.

kimbo's accertation ... a "what if".

Euphol as a cofactor looks like a safe bet. I don't know of anything else that could explain "tripartite synergism."

Is euphol a pphytoandrogen?

Yes

Or are you suggesting ingesting euphol in addition to phytoadrogens is somehow going to increase their bioavailability?

No

The flaw here lies in your addition of ecdysterone.

Again, just trying to get a handle on what the oral bioavailability of euphol might be.

Don't hang on my every word here. Once I left steroid metabolism and started on cofactors my expertise went out the window.

[Heavy_Lifter85]

Curr Med Chem. 2008;15(1):75-91. Links
Phytoecdysteroids and anabolic-androgenic steroids - structure and effects on humans.
Báthori M, Tóth N, Hunyadi A, Márki A, Zádor E.

Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Eötvös utca 6., Hungary. Bathori@pharma.szote.u-szeged.hu.

Phytoecdysteroids are structural analogs of the insect molting hormone ecdysone. Plants comprise rich sources of ecdysteroids in high concentration and with broad structural diversity. Ecdysteroids have a number of proven beneficial effects on mammals but the hormonal effects of ecdysteroids have been proven only in arthropods. Their structures are somewhat similar to those of the vertebrate steroid hormones but there are several structural differences between the two steroid groups. Despite of these essential structural differences, ecdysteroids exert numerous effects in vertebrates that are similar to those of vertebrate hormonal steroids, and they may serve as effective anabolic, hepatoprotective, immunoprotective, antioxidant and hypoglycemic agents. Ecdysteroids do not bind to the cytosolic steroid receptors, instead, they are likely to influence signal transduction pathways, like the anabolic steroids, possibly via membrane bound receptors. The application of phytoecdysteroids is a promising alternative to the use of anabolic-androgenic steroids because of the apparent lack of adverse effects. The prospective use of phytoecdysteroids may extend to treatments of pathological conditions where anabolic steroids are routinely applied. One of the most cited aspects of phytoecdysteroid application (on the Internet) is the increase of muscle size. However in this field too stringent research is needed as an adequate cytological explanation is not yet available for the anabolic. This paper reports on the most important structural differences between androgenic hormones, their synthetic analogs and ecdysteroids. The anabolic/hormonal effects and the possible mechanisms of action of these compounds are also discussed as concerns the skeletal muscle.

[Jakeshorts]

Don't hang on my every word here. Once I left steroid metabolism and started on cofactors my expertise went out the window.

if your just throwing out conjectures and aren't welcoming comments then say so.

otherwise i'm gonna keep saying things like - what exactly does ecdy DO and how would you measure it's bioavailability? The study above isn't really saying anything at all. I already posted a study that mentions an anabolic effect but the one you posted admits it's nonhormonal. Slight structure difference could mean a world of difference. I think your grasping for straws at this point.

[Heavy_Lifter85]

if your just throwing out conjectures and aren't welcoming comments then say so.

I'm just posting my thoughts on the subject, comments are welcome.

what exactly does ecdy DO

I don't know. It seems no one knows at this point.

and how would you measure it's bioavailability?

I'm not trying to measure anything quantitatively, I just wonder if there is data on the metabolism of ecdy by P-450 in the liver. If ecdy is extensively metabolized, it may offer some insight into the action of P-450 on euphol.

EDIT: OK, I see the above was not made clear in previous posts, perhaps causing your frustration. Have some patience with the plebian forum members outside the IC .

The study above isn't really saying anything at all. I already posted a study that mentions an anabolic effect but the one you posted admits it's nonhormonal.

Yes, nonhormonal - which is very significant. It says that ecdy's MOA does not involve directly binding the AR. Which means it may act as a cofactor - like euphol.

Slight structure difference could mean a world of difference. I think your grasping for straws at this point.

There's not too much in the literature about euphol. I'm just posting my thoughts here.

I'm not trying to be hostile; please tone down your posts.

[Jakeshorts]

apologies for the tone heavy.

I'll repost this here: not sure if you saw it or not

Mechanism of the anabolic action of phytoecdisteroids in mammals][Article in Russian]


Syrov VN.
In experiments with white mice it has been established that phytoecdisteroides turkesteron, ecdisteron and 2-desoxy-alpha-ecdison in the dose of 5 mg on 1 kg of body mass stimulate the protein synthesis. Using the model of protein synthesis from mice liver it has been shown that the action of phytoecdisteroides is connected with the rise of poliribosome functional activity and rate increase of protein macromolecules formation. Preliminary administration of actinomycin D does not prevent the effect of protein synthesis stimulation. It has been concluded that the anabolic effect of phytoecdisteroides in mammals organism is connected not with induction of RNA synthesis but with the acceleration of translocation processes.

PMID: 6525371 [PubMed - indexed for MEDLINE]



My confusion is you keep bringing of AR binding - yes it doesn't bind to AR, nor does it act on ANY hormone whatsoever. So it's MOA compared to ANY hormonal compound is a moot point.

Do you have any literature discussing the significance of euphol?

[Heavy_Lifter85]

It has been concluded that the anabolic effect of phytoecdisteroides in mammals organism is connected not with induction of RNA synthesis but with the acceleration of translocation processes.

There we go; the mechanism is becoming clear now.

My confusion is you keep bringing of AR binding - yes it doesn't bind to AR, nor does it act on ANY hormone whatsoever. So it's MOA compared to ANY hormonal compound is a moot point.

Right, I see that now. During the course of this thread my understand of ecdy has gone from AR ligand to possible cofactor to accelerator for translocation. The trouble with applying what one knows about concept A (AR, steroid ligands, etc) to concept B (phytoandrogens), without much research on the new subject, is that you start from square one and make lots of errors along the way. I'll learn the basics before posting on a topic from now on - this ain't bb.com

Do you have any literature discussing the significance of euphol?

Just what has been posted in the various threads here. I've got an exam this evening and need to drop this thread for the day.

[Jakeshorts]

I'm notorious for the same thing. We can learn together, I had just assumed you saw my post in the other thread.

[Kimbo]

Yeah, my statement with regard to phyoandrogens was a "what if" statement based on the supposed mechanism of action of some phytoestrogens. This was mostly a statement made to suggest that we need more information.