Updated Research and Knowledge - Cutting Edge

[tiktok]

Hey Chemical, I was wondering, can oleuropein penetrate the skin without problem, given that it is a fairly large molecule?

Looks like it's right around the 500 dalton limit at 540.52 Daltons

[Seuxin]

540 daltons oO ? Is it possible to use it properly ???

[Chemical]

In order to increase PGE2, you should look at Vitamine E Succinate studies. By the way, i use adenosine since 7 month with really no results

I have difficutlies to find a good oleuropein supplement to buy which can be shipped to France... Better is to buy as liquide, ethanol based right ?

Any link for Europe please ?

Thanks a lot

Do you remember the names of any particular studies that show vitamin E succinate increasing pge2? (because I cant seem to find any or I'm just being lazy)

You can try contacting this seller to see if they ship their liquid oleuropein to france http://www.amazon.co.uk/gp/aag/main?...RJRO&sshmPath=

As a last result you can make your own oleuropein solution, it'll be a bit more expensive and time consuming to mix the liquids in the right amounts but unfortuneately thats the best option you have. Its still ridiculously cheap if you think about how long it will last you. I'm reducing my application dose to 0.5ml because I'm starting to think that less might be more effective.

Ascorbic acid =

COX2 inhibitor
Prolactin activator
Hypoxia inhibitor
CD34 inhibitor

upregulates these genes that are already overexpressed in balding scalp:

2) IGF-1(not an immune marker- but it is already overupregulated in balding scalp)
3)c-FOS apoptotic gene
4)CTSK(this gene breaks down bones- and hair):
Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation
Tocris Summary for CTSK Gene

http://www.genecards.org/cgi-bin/carddisp.pl?gene=CTSK&keywords=ctsk

5)CXCL9:
Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3

6)C3: C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.

Sorry but If u're claiming that these immunity genes are not the 1s causing balding- then what is? MpB is not an atuimmune condition? do u have any idea what does CRTh2 stands for?

We are 'manually' controlling which protein and receptor? a net increase in hair growth by what mechanism? what are the factors that you are talking about? What's the altenative pathway? I can only see a long detour here

Ah, I see now why you think Vitamin C is bad. You hold the belief that Androgenetic Alopecia/MBP is an autoimmune condition. I'll tell you straight, its not. AGA is not Alopecia Areata. It is androgen dependent, and Androgens are the cause of baldness. The androgen receptor and DHT both reduce hair growth via AR mediated signalling pathways including: Beta Catenin suppression (I'll go into this), DKK1, and 3BetaDiol which is a metabolite of DHT. I'm not sure where you got your theory that immunity markers cause T cells to attack DPC and cause baldness. You will have to explain this to me if you think I'm not understanding it.

CRTH2 is the Prostaglandin DP2 receptor correct? I'm not sure what youre suggesting here with this. PGD2 elevation might be a causative factor but I believe its more of a side effect rather than the initiator. Immunity markers are simply markers. They are indicative of other agents causing these markers to be expressed. Like inflammation.

Furthermore, IGF-1 is NOT elevated in the balding scalp, it is reduced. IGF-1 is good for hair and actually stimulates regrowth. Coming back to Ascorbic Acid, I did say this:

Its not Vit.c specifically that we're after, we need a good ROS scavenger, since the studies I posted in my first page show that ROS scavengers like ascorbate completely reverse the effects of DHT mediated hair growth inhibition. Your statement implies vitamin C does not help with hair growth/or causes hair to stop growing, which I disagree with for the aformentioned reasons.

You might have missed it or maybe I wasnt clear enough. Ascorbic Acid was merely an example that gave us a starting point in finding a suitable ROS scavenger. If we disregard your assumption that AGA is an autoimmune condition, Vitamin C could be therapeutic as it increases hair growth.

Addressing your question of the pathways:



It seems as though you've not read any of my posts about the treatments available to use to against hair loss. Minoxidil, oleuropein, ketoconazole, emu oil. They all have mechanisms that target different pathways. Look at the diagram.

I always though there was no point in taking things that stimulate growth like minox or now Oleuropein if you dont take something that halts or slows down the balding process. The explanation that I had read for this was that it didnt matter if your hair was thicker (because of minox/Oleuropein) because the follicles were gonna die anyway, as you werent attacking the root of the problem (and supposedly finasteride would attack the 'root' as it lowers dht).

Maybe i got everything wrong, but it would be great if you could explain this to me, as i dont really understrand why would you take something like Oleuropein (which from what i understand only stimulates growth) without taking something that would stop or slow the death of the follicle? Does this question make sense? Its like why would you want to make your hair thicker if its going to fall off anyway.
Thanks for your time i really appreciate what youre doing

This question hasnt been asked before and it's a very valid question that I havent directly addressed. In short, unless you can deactivate the Androgen Receptor permanently or permanently interfere with the Androgen signalling pathway, you will not be able to come off treatment. Alternatively if a treatment can reduce AR with a long half life, you can kind of call that a semi permanent cure, since you dont need to use it everyday. The root cause is the AR, and the various extension pathways that reduce hair growth like DHT metabolites and DHT induced DKK1 which act in a paracrine manner (cells that release proteins that bind to nearby cells surface). Yes, the hair will fall out if you stop the treatment, but it will stop the shedding, AND regrow hair. So long as you stay on the treatment, you'll keep your hair. Its a battle against on your genes. Furthermore, not many people know this but minoxidil dose dependantly inhibits AR activity by around 50% in the presence of DHT (and this is with 5% minoxidil with an assumed absorption rate of ~1.7%). Imagine if you bumped up the dose to 10% or used it along side emu oil for enhanced skin penetration. How does it do this? Minoxidil binds to the AR and interferes with its co-activators rendering most of the AR useless, but not completely. The androgen receptor on the other hand competes with TCF for BetaCatenin. If TCF cannot bind with Beta Catenin, you wont see any hair growth, and instead the DPC will secrete factors that will inhibit the growth of nearby DPC in a paracrine manner that I just mentioned earlier. We need to find agents that will interfere with Androgen Receptor signalling, or co-activators, that way we can avoid Anti-androgens and still achieve Androgen receptor inhibition.

Funnily enough, Beta Catenin has been found to inhibit Filamin A which Androgen Receptors require to function. So if you increase BetaCatenin, which you need to anyway to regrow and keep hair, you can also shut down the AR. Now the challenge is to find something that increases betacatenin consistently and can cause a prolonged increase.

Regarding your question about what oleuropein will do stop the root cause, if you look the diagram above you can see that oleuropein inhibits DKK1, which DHT increases via P53. This is one of the ways that DHT kills hair follicles. Oleuropein also stimulates BetaCatenin via WNT10b, and IGF-1 which has the potential to regrow hair via PDGF-a/b upregulation. I'm using minoxidil, and I advocate minox for its androgen receptor suppressing effects.

Heres the science behind all of what I just said, feel free to skip this part:

Minoxidil may suppress androgen receptor-related functions

All of the above data were obtained in prostate cancer cell lines or in in vitro studies. To extend these findings to skin cells, we tested whether minoxidil has similar effects in HHDPCs (human hair dermal papilla cells) using an AR reporter assay. AR expression in HHDPCs was confirmed at mRNA (Fig. (Fig.4A)4A) and protein (Fig. (Fig.4B)4B) levels. As shown in Fig. Fig.4C,4C, minoxidil suppressed AR transcriptional activity in a concentration-dependent manner (compare lanes 4 and 5 to lane 2). We further tested minoxidil effects on AR protein stability in HHDPCs. As shown in Fig. Fig.4D,4D, minoxidil induced a concentration-dependent reduction in AR protein stability. These data provide further evidence that the efficacy of minoxidil in treating AGA may involve suppression of AR-related functions.



Interestingly, our structural studies demonstrated that minoxidil is chelated at a novel, previously unreported groove in the AR. The residues surrounding the groove provide hydrophobicity at the surface, whereas the inner core exhibits hydrophilic properties, implying selectivity for binding factors. Moreover, the groove is also located opposite to and at a distance from AF-2 and BF-3 sites [48]; accordingly, it may represent a new candidate site for the interaction of AR coregulators (Fig. (Fig.3D).3D). To date, there have been few reports on AR structure and none has described the role of the groove identified here in AR action. Mutation of a nearby residue, Cys784, to Tyr784 in the α8 helix was reported to cause the loss of transactivation activity in a female patient [49]. In our model, variations in this region resulted in steric clashes or changes in secondary structure. By occupying this grove, minoxidil may hinder the physical association of interacting proteins, thereby disrupting downstream regulation of AR transactivation. Taken together with mutagenesis data, our structural findings suggest that this groove may be important for binding of AR-interacting proteins during transactivation. The minoxidil-AR-LBD co-crystal model thus may provide a platform for the further development of drugs for the treatment of AGA and other androgen-AR pathway-related diseases

-----------------------

The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells

Conversely, Filamin A (FlnA), which is required for AR activation in response to androgen stimulation (Castoria et al., 2011; Mooso et al., 2012), was significantly downregulated by β-catenin activation, an effect that was antagonized by testosterone (Supplementary Figure S5c online). The observation that testosterone increased FlnA expression in the presence of 4-OHT is consistent with the conclusion that AR signaling antagonized β-catenin signaling. As 4-OHT treatment led to a major reduction in FlnA, it is not surprising that there was no further effect of bicalutamide.

As a side note they reported the same finding of BetaCatenin stimulating PDGF-a expression which we know causes the formation of new hair follicles.

Sustained β-catenin activation in combination with AR inhibition led to an increase in platelet-derived growth factor receptor-α-positive (Figure 5a) and Vimentin-positive (Figure 5d) fibroblasts adjacent to ectopic HFs.

Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis.

BCT = beta-catenin-T-cell factor (Tcf) signalling pathway

These data suggest that in steady-state conditions, AR has the ability to compete out Tcf binding for beta-catenin. Finally, using SW480 cells, we show that AR-mediated repression of the BCT pathway has implications for cell cycle progression and in vitro growth. Using FACs analysis, we observed a 26.1% increase in accumulation of cells in the G1 phase of the cell cycle, while in vitro growth assays showed a 35% reduction in viable cells transfected with AR+DHT treatment. Together, our data strongly suggest that a reciprocal balance of nuclear beta-catenin facilitates AR-mediated repression of BCT-driven transcription and cell growth.

Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor.

Importantly, this TCF4 construct was unable to prohibit ligand-dependent repression of CRT (Figure 8e), implying that TCF4 competes with AR for beta-catenin. Thus, the pivotal factor underlying ligand-dependent inhibition of CRT by AR could be beta-catenin. This outcome with wildtype TCF4 over-expression (Figure 8e, full length) may represent a general property of all TCF/LEF family members, as ectopic expression of LEF1 likewise mollifies the effects of androgen signaling on CRT (Figure 8f). Noticeably, LEF1 synergized with mutant beta-catenin to potentiate CRT.

Also, Genistein Combined Polysaccharide is an effective Filamin A inhibitor.But its quite pricy: http://www.amazon.com/GeniKinoko-500.../dp/B002YE8232

Hey Chemical, I was wondering, can oleuropein penetrate the skin without problem, given that it is a fairly large molecule?

I completely missed this fact. Could this mean oleuropein cant do anything?

I did however see this article:

https://www.futurederm.com/what-exac...0-dalton-rule/

Molecules that are of a small enough weight are able to penetrate through the layers of the skin and be absorbed. This weight is generally considered to be 500 Daltons (Experimental Dermatology). After review, researchers found that there were no ingredients that were effective when much larger than 500 Daltons, though there are some that are still effective at slightly larger than 500 Daltons. Common allergens also tend to be under 500 Daltons.

And, yet, there are still some exceptions to this rule. For example, atopic dermatitis can be treated with derivatives tacrolimus, which is 822 Daltons, and ascomycin, which is 811 Daltons. But, generally speaking, researchers suggest that anything intended for medicinal purposes be smaller than 500 Daltons to assure absorption.

I wonder if mouse skin has a different limit?

[TheKingofFighters]

Ah, I see now why you think Vitamin C is bad. You hold the belief that Androgenetic Alopecia/MBP is an autoimmune condition. I'll tell you straight, its not. AGA is not Alopecia Areata. It is androgen dependent, and Androgens are the cause of baldness. The androgen receptor and DHT both reduce hair growth via AR mediated signalling pathways including: Beta Catenin suppression (I'll go into this), DKK1, and 3BetaDiol which is a metabolite of DHT. I'm not sure where you got your theory that immunity markers cause T cells to attack DPC and cause baldness. You will have to explain this to me if you think I'm not understanding it.

Theory? it's From Dr Cotsareli's patent page 91-92 under 'IMAGES' http://www.google.com/patents/US20110021599

CRTH2 is the Prostaglandin DP2 receptor correct? I'm not sure what youre suggesting here with this. PGD2 elevation might be a causative factor but I believe its more of a side effect rather than the initiator. Immunity markers are simply markers. They are indicative of other agents causing these markers to be expressed. Like inflammation.

Initiator of what? Side effect of what? So u're saying 'inflammation' is what is causing the rise of PGD2 n not the other way around? Not to mention that PGD2 is not the only factor for all the inflamamtion is MPB- based on Dr Cotsareli's patent

Furthermore, IGF-1 is NOT elevated in the balding scalp, it is reduced. IGF-1 is good for hair and actually stimulates regrowth. Coming back to Ascorbic Acid, I did say this:

IGF-1 is not elevated in balding scalp??? Take a look yourself page 81 under 'IMAGES' http://www.google.com/patents/US20110021599 by Dr Cotsarelis

You might have missed it or maybe I wasnt clear enough. Ascorbic Acid was merely an example that gave us a starting point in finding a suitable ROS scavenger. If we disregard your assumption that AGA is an autoimmune condition, Vitamin C could be therapeutic as it increases hair growth.

So what's your assumption based on that MPB is not an autoimmune disorder? you clearly meant to suggest that Ascorbic acid was effective at addressing MPB- and AS upregulates at least 6 genes unbeneficially in bald scalp.

Addressing your question of the pathways:

It seems as though you've not read any of my posts about the treatments available to use to against hair loss. Minoxidil, oleuropein, ketoconazole, emu oil. They all have mechanisms that target different pathways. Look at the diagram.

what makes u think i have not read or USED for that matter(in fact, i've used 3 of that 4 items u have just listed out in that paragraph)

This question hasnt been asked before and it's a very valid question that I havent directly addressed. In short, unless you can deactivate the Androgen Receptor permanently or permanently interfere with the Androgen signalling pathway, you will not be able to come off treatment. Alternatively if a treatment can reduce AR with a long half life, you can kind of call that a semi permanent cure, since you dont need to use it everyday. The root cause is the AR, and the various extension pathways that reduce hair growth like DHT metabolites and DHT induced DKK1 which act in a paracrine manner (cells that release proteins that bind to nearby cells surface). Yes, the hair will fall out if you stop the treatment, but it will stop the shedding, AND regrow hair. So long as you stay on the treatment, you'll keep your hair. Its a battle against on your genes. Furthermore, not many people know this but minoxidil dose dependantly inhibits AR activity by around 50% in the presence of DHT (and this is with 5% minoxidil with an assumed absorption rate of ~1.7%). Imagine if you bumped up the dose to 10% or used it along side emu oil for enhanced skin penetration. How does it do this? Minoxidil binds to the AR and interferes with its co-activators rendering most of the AR useless, but not completely. The androgen receptor on the other hand competes with TCF for BetaCatenin. If TCF cannot bind with Beta Catenin, you wont see any hair growth, and instead the DPC will secrete factors that will inhibit the growth of nearby DPC in a paracrine manner that I just mentioned earlier. We need to find agents that will interfere with Androgen Receptor signalling, or co-activators, that way we can avoid Anti-androgens and still achieve Androgen receptor inhibition.

Funnily enough, Beta Catenin has been found to inhibit Filamin A which Androgen Receptors require to function. So if you increase BetaCatenin, which you need to anyway to regrow and keep hair, you can also shut down the AR. Now the challenge is to find something that increases betacatenin consistently and can cause a prolonged increase.

that's what any1 with some decent knowledge in hairloss mechansims would say too.

Regarding your question about what oleuropein will do stop the root cause, if you look the diagram above you can see that oleuropein inhibits DKK1, which DHT increases via P53. This is one of the ways that DHT kills hair follicles. Oleuropein also stimulates BetaCatenin via WNT10b, and IGF-1 which has the potential to regrow hair via PDGF-a/b upregulation. I'm using minoxidil, and I advocate minox for its androgen receptor suppressing effects.

Really? even the title of the study says that the authors are'nt exactly conclusive of that purported effect of minoxidil. If it's true- i guess those using Minoxidil concomitantly with RU or Dut while should stop wasting money on the latter 2.

'Minoxidil may suppress androgen receptor-related functions'

Dkk1 could be upregulated not by just p53- it could also be done so by BMP4, Hairless, VDR and Retinoic acid receptors

[tiktok]

I completely missed this fact. Could this mean oleuropein cant do anything?

Strangely Ketoconazole has a weight of 531 daltons, so if the theory were exact, then it should not be effective either.

Also worth noting that limit changes based on the condition and type of skin:



I'd say it's a prime candidate for use with light dermarolling (which is how I intend on using it).

[FeelsBad]

Anyone have a US source for oleupurein? Preferably an alcohol tincture.

[potato1987]

Does emu oil help absorption at all? It's a shame Foillicept don't just sell the vehicle they created.

[Chemical]

Theory? it's From Dr Cotsareli's patent page 91-92 under 'IMAGES' http://www.google.com/patents/US20110021599

Initiator of what? Side effect of what? So u're saying 'inflammation' is what is causing the rise of PGD2 n not the other way around? Not to mention that PGD2 is not the only factor for all the inflamamtion is MPB- based on Dr Cotsareli's patent

IGF-1 is not elevated in balding scalp??? Take a look yourself page 81 under 'IMAGES' http://www.google.com/patents/US20110021599 by Dr Cotsarelis

So what's your assumption based on that MPB is not an autoimmune disorder? you clearly meant to suggest that Ascorbic acid was effective at addressing MPB- and AS upregulates at least 6 genes unbeneficially in bald scalp.

what makes u think i have not read or USED for that matter(in fact, i've used 3 of that 4 items u have just listed out in that paragraph)

Really? even the title of the study says that the authors are'nt exactly conclusive of that purported effect of minoxidil. If it's true- i guess those using Minoxidil concomitantly with RU or Dut while should stop wasting money on the latter 2.

'Minoxidil may suppress androgen receptor-related functions'

Dkk1 could be upregulated not by just p53- it could also be done so by BMP4, Hairless, VDR and Retinoic acid receptors

I think we're going to have to agree to disagree on these topics. If you think you're right and I'm wrong then thats fine too, I'll continue in my ignorance. You're not posting any real evidence (I couldnt find anything in that patent supporting what you've said - I might just be blind) and aren't contributing anything meaningful or constructive to this discussion.

You were right about PGD2 leading to inflammation via the CRTH2 receptor, but it can also reduce inflammation:

Collectively, these results show that when hematopoietic PGD synthase is overexpressed, tissue resident cell-derived PGD2 suppresses skin inflammation via DP in the early phase, but hematopoietic lineage cell-derived PGD2 stimulates CRTH2 and promotes inflammation during the late phase. DP-mediated vascular barrier enhancement or CRTH2-mediated neutrophil activation may be responsible for these effects. Thus, PGD2 represents opposite roles in inflammation, depending on the disease phase in vivo.

Also:

Insulin-like growth factor-1: roles in androgenetic alopecia.

Abstract
Of all the cytokines or growth factors that have been postulated to play a role in hair follicle, insulin-like growth factor-1 (IGF-1) is known to be regulated by androgens. However, how IGF-1 is altered in the balding scalp has not yet been investigated. In this study, expressions of IGF-1 and its binding proteins by dermal papilla (DP) cells obtained from balding versus non-balding hair follicles were quantified using growth factor array. DP cells from balding scalp follicles were found to secrete significantly less IGF-1, IGFBP-2 and IGFBP-4 (P < 0.05) than their non-balding counterparts. Our data confirmed that the downregulation of IGF-1 may be one of the important mechanisms contributing to male pattern baldness.

So this study is bullshit according to Dr Cotsarelis?

Moreover, the title is not the conclusion. Theres a difference:

Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

VDR is there in the diagram. DHT upregulates VDR via ER Beta too. DHT is known to increase DKK1 in the scalp: Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes.
If you know of any other pathways then please contribute evidence.

I shouldnt be the one to support your own claims with evidence, thats your job. Telling people to go and google it or find it isnt useful, you dont see me doing that do you? If you're going to continue with this behaviour then dont waste your time, or my time too because it just pollutes the thread. I wont be responding to your posts because you seem to be trying to evoke a reaction from me.

Strangely Ketoconazole has a weight of 531 daltons, so if the theory were exact, then it should not be effective either.

Also worth noting that limit changes based on the condition and type of skin:

I'd say it's a prime candidate for use with light dermarolling (which is how I intend on using it).

From that graph, it looks like oleuropein and keto have a 70% absorption rate. Its not too bad and theres still potential.

Does emu oil help absorption at all? It's a shame Foillicept don't just sell the vehicle they created.

Apparently Emu Oil aids with skin permeation but that might just be for itself.

Interestingly:

Relative influence of ethanol and propylene glycol cosolvents on deposition of minoxidil into the skin.
Abstract
Minoxidil, a potent antihypertensive, is moderately effective in the treatment of hair loss when it is applied to the scalp as a 2% solution in 60% ethanol, 20% propylene glycol and 20% water. Important questions remain concerning both the mechanism of delivery and the pathway of penetration of this drug from its ternary solvent system. Since preliminary studies in our laboratory indicated that water in the formulation influenced permeation far less than the other two solvents, we examined the relative deposition and penetration influences of binary combinations of ethanol and propylene glycol. When 50 microL/cm2 of the formulations was spread over hairless mouse skin sections mounted in Franz diffusion cells, only small amounts of minoxidil were actually recovered from the receiver compartments. Nevertheless, more minoxidil penetrated the skin as the proportion of ethanol in the mixtures was increased. To determine if these in vitro results formed a representative picture of the in vivo behaviors of these vehicles, selected deposition experiments were performed on live, anesthetized mice under experimental conditions similar to those used in the diffusion cell work. The good agreement between in vivo and in vitro studies may be a result of the relatively fast partitioning of the drug into the skin as compared to its diffusion through the skin.

Ethanol disrupts the lipid barrier of the stratum corneum:

In conclusion, 80% EtOH/20% PG enhanced the percutaneous absorption of aspirin by perturbing the macroscopic barrier integrity of the stratum corneum and through a loss of stratum corneum lipids.

Continuing on the research for AR antagonism, I've found some leads:

Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer.

To explain its antigrowth effect on PCa cells, we found that EGCG physically interacts with the AR-LBD and competes with natural agonist DHT (IC50 0.4 μM). The cell growth assay was also in concordance with this result, and EGCG in fact abrogated the proliferative effect of strong synthetic agonist R1881 on PCa cells, and hence serves as a functional antagonist. It is important to mention here that the most widely used AR antagonists have been the steroidal drug cyproterone and the nonsteroidal drugs flutamide and bicalutamide, which are all competitive antagonists of androgen binding.

Another study:

Effects of topical application of EGCG on testosterone-induced hair loss in a mouse model

These results suggest that T injection in this mouse model can induce hair loss through apoptosis of hair follicles. EGCG can reduce the T-induced hair loss by down-regulating the apoptosis of follicular epithelial cells and even stimulate hair re-growth.

Effect of T injection and EGCG on AR, 17β- and 3β-hydroxysteroid dehydrogenase (HSD) expression of hair follicles

We examined the effect of T on AR expression by IHC staining. IHC of AR demonstrated that the T + vehicle group had 50–70% staining intensity in follicular epithelial cells as well as sebaceous glands, whereas the T + EGCG group had <10% staining in follicular epithelial cells (Figure S1 and Table S1). IHC staining for 17β- and 3β-HSD was also performed to determine whether there were changes in the androgen pathway by T or EGCG. However, there was no difference in 17β- and 3β-HSD expression among the T-injected and T + EGCG groups (unpublished data). These results demonstrate that EGCG can down-regulate T-induced AR expression of hair follicular cells but has no effect on 17β- and 3β-HSD expression.

Testosterone increased AR activity, hence the 50-70% staining. However, when EGCG was present, there was less than 10%.

EGCG has a molecular weight of 458 which is good.

Topical absorption shows promise:

In vivo human skin penetration of (-)-epigallocatechin-3-gallate from topical formulations.
Abstract
The aim of the study was to examine the effect of topical vehicles on the in vivo human stratum corneum penetration of the antioxidant and skin photoprotective agent (-)-epigallocatechin-3-gallate (EGCG). Model oil-in-water (o/w) emulsion and gel formulations containing 1 % (m/m) EGCG were prepared and subjected to photodegradation studies in order to select excipients that minimize the light instability of EGCG. The optimized emulsion and gel were applied to human volunteers and the EGCG percutaneous permeation was evaluated in vivo by the tape- -stripping technique. No significant differences in the percentage of the applied EGCG dose diffused into the stratum corneum were observed between the o/w emulsion (36.1 ± 7.5 %) and gel (35.5 ± 8.1 %) preparations. However, the amount of EGCG permeated into the deeper region of human stratum corneum was significantly larger for the o/w emulsion compared to the gel. Therefore, the emulsion represents a suitable vehicle for topical delivery of EGCG.

They didnt notice a huge difference using the oil in water emulsion vehicle on the diffusion rate, but it did enhance stratum corneum permeation.

The mice study used 10% EGCG and ethanol:

Histologic findings of the upper dorsal skin stained with haematoxylin and eosin (a–f), and TUNEL staining (g–l). Topical application of 10% EGCG (a, g), testosterone (T)’s vehicle injection (b, h), T injection (c, i), T injection + topical application of EGCG vehicle (ethanol) (d, j), T injection + topical application of 10% cyproterone acetate (e, k) and T injection + topical application of EGCG (f, l). [(a–f) × 100, (g–l) × 400].

Since ethanol reduces the barrier function of the SC, EGCG might be readily absorbed. I'm going to try this after christmas break because it could be the an effective agent to use alongside minox to inhibit AR.

[pilipili]

Thank you for your amazing work. It’s worth giving it a try. But If I may, do you think mixing ginkgo and olive tincture is a good idea ? And what If I also use adenosine, azelaic acid and vitamin E succinate in my regimen. thank you for your advices

[scooterboy]

Chemical. are you applying this once or twice a day ?

[solaeg]

Thank you for your contributions, Chemical.

I'm not sure whether it has been covered but this suggests that specifically hydroxytorosol (oral intake in men) inhibits PGF2a: http://www.ncbi.nlm.nih.gov/pubmed/11095986
I believe bim works as an PGF2 analogue. Could the topical (or oral) intake of olive leaf extract countereffect that? Or maybe one that is standardized to hydroxytorosol, thus inhibiting PGF2a? Or is that perhaps why PGE1/2 is needed besides oleuropein?

[solaeg]

Double post

[Keeper]

Hey Chemical!


I like your way of approaching things !
So i decide to support you a little bit and to talk to a huge german company which is specialized in production of oleuropein extract (for around 20 years) in all possible concentrations and also Emu Oil.
After some conversation they said: if we can show them a summary of your theory that makes kind of sense and we have a plan how to conduct a study they would probably produce a liquid in a concentration we want (also with emu oil or what else is necessary) and send free samples to us to try it for an amount of time (probably 50-100 people). Of course we would have to make pictures and give protocols about our experience and so on but I think this should stop us. She said to start it before christmas would be unrealistic, but very soon in the new year!!!!

Sounds not that bad or?

[Keeper]

I know its not that easy.
But would be nice if we could all cooperate together and figure out a plan and also with the help of experienced members about how to design a survey based on this.

[trunks]

They should do preclinical trial with ~60 ppl on their own, with professional tools, documentation and so on.

Oleuropein, Minoxidil and placebo would be the best.

I probably couldnt participate even remotely becouse I dont want to drop my current regimen.