P144 - topical tgf-beta inhibitor

[Strange Days]

Could this be useful for us?

Topical Application of a Peptide Inhibitor of Transforming Growth Factor-bold beta1 Ameliorates Bleomycin-Induced Skin Fibrosis

Topical application of P144 significantly reduced skin fibrosis and soluble collagen content. Most importantly, in mice with established fibrosis, topical treatment with P144 lipogel for 2 wk significantly decreased skin fibrosis and soluble collagen content. Immunohistochemical studies in P144-treated mice revealed a remarkable suppression of connective tissue growth factor expression, fibroblast SMAD2/3 phosphorylation, and alpha-smooth muscle actin positive myofibroblast development, whereas mast cell and mononuclear cell infiltration was not modified. These data suggest that topical application of P144, a peptide inhibitor of TGF-beta1, is a feasible strategy to treat pathological skin scarring and skin fibrotic diseases for which there is no specific therapy.

They also criticise systemic tgf-beta inhibition:

Systemic inhibition of TGF-beta, however, raises important safety concerns, because this factor displays pleiotropic and potent effects in immunomodulation, inflammation, and tumor development (Akhurst, 2002). Consistently, in TGF-beta1-deficient mice, skin scarring is reduced but they develop a severe wasting syndrome accompanied by a generalized inflammatory response and tissue necrosis, resulting in organ failure and death.

Therefore, local rather than systemic TGF-beta inhibition, or targeting of downstream factors involved in TGF-beta profibrotic signaling represent alternative strategies for the development of anti-fibrotic therapies.

 

[docj077]

Good find. That's what we need.

 

[michael barry]

This is good news. I hope they run a hairloss trial with it.


I wonder if apple cider vinegar is very good at inhibiting TGF beta? Surely it has some proanthocyandin oligomers therein?


Noticing the side effects of internal tgf suppression, I can see why a man would not want to do this. Those are some tough side effects.


Doctor, you really may have "found" a big piece of the puzzle with your idea. I hope your regimine is bearing fruit for you, M.

 

[docj077]

This is good news. I hope they run a hairloss trial with it.


I wonder if apple cider vinegar is very good at inhibiting TGF beta? Surely it has some proanthocyandin oligomers therein?


Noticing the side effects of internal tgf suppression, I can see why a man would not want to do this. Those are some tough side effects.


Doctor, you really may have "found" a big piece of the puzzle with your idea. I hope your regimine is bearing fruit for you, M.

I didn't "find" anything. Foote's "lymphedema theory" pissed me off so much that I just ended up reading through countless research articles until I found something that made sense.

I don't deserve any credit and I really don't want any, either.

 

[abcdefg]

Doctor whats the best at reducing tgf beta today? Is it safe to even try?

 

[docj077]

Doctor whats the best at reducing tgf beta today? Is it safe to even try?

Internally? Nothing is really safe. Curcumin or internal polycyanidins are a possibility. Unfortunately, no one knows the long term consequences of TGF-beta inhibition when using drugs to inhibit the molecule.

Wait for a topical TGF-beta inhibitor. It should help a lot when it hits the market...whenever that will be. :cry:

 

[Old Baldy]

Michael and Doctor: You might already know this but hydrangea root powder proportedly acts to inhibit TGF beta. Make a classic 125 gram powder mixed in 500ml of 100 proof vodka, shake every day, release pressure by opening the cap after shaking and, in two weeks, strain and use the stuff on your scalps.

You guys might know it as amacha?

 

[abcdefg]

ah ok thanks. I hate not having any medical background because you cant understand anything these studies talk about. Im thinking about propecia, but without a strong family history of male pattern baldness im not sure if its male pattern baldness or not. Propecia is a pretty drastic step if you have little family history of male pattern baldness.

 

[Riordan]

Michael and Doctor: You might already know this but hydrangea root powder proportedly acts to inhibit TGF beta. Make a classic 125 gram powder mixed in 500ml of 100 proof vodka, shake every day, release pressure by opening the cap after shaking and, in two weeks, strain and use the stuff on your scalps.

You guys might know it as amacha?

amacha is in Waseda's Amasisho concoction and in Elsom Research product called the Formulator.

 

[Old Baldy]

You can still get hydrangea root powder from Ancient Way (and many other places) but amacha is hard to find in the USA, unless someone started carrying it recently.

 

[Beethoven]

Doctor whats the best at reducing tgf beta today? Is it safe to even try?

Internally? Nothing is really safe. Curcumin or internal polycyanidins are a possibility. Unfortunately, no one knows the long term consequences of TGF-beta inhibition when using drugs to inhibit the molecule.

Wait for a topical TGF-beta inhibitor. It should help a lot when it hits the market...whenever that will be. :cry:

docj077, what's your opinion on trying to make homemade topical?
What I mean is adding crushed Curcumin to minoxi solution.
I assume that there are no studies about the effectivness of topical curcumin, and even if it's effective we don't know if the alcoholic minoxi solution will be a good vehicle, or maybe they might interact and lose their activity.
What's your opinion? worth trying?

 

[docj077]

Doctor whats the best at reducing tgf beta today? Is it safe to even try?

Internally? Nothing is really safe. Curcumin or internal polycyanidins are a possibility. Unfortunately, no one knows the long term consequences of TGF-beta inhibition when using drugs to inhibit the molecule.

Wait for a topical TGF-beta inhibitor. It should help a lot when it hits the market...whenever that will be. :cry:

docj077, what's your opinion on trying to make homemade topical?
What I mean is adding crushed Curcumin to minoxi solution.
I assume that there are no studies about the effectivness of topical curcumin, and even if it's effective we don't know if the alcoholic minoxi solution will be a good vehicle, or maybe they might interact and lose their activity.
What's your opinion? worth trying?

Curcumin as a topical isn't really all that feasible right now. Curcumin stains the skin a yellowish color and even touching the capsules that the herb comes in can lead to the powder getting everywhere. Applying it to areas with male pattern baldness is possible, but I'd wait until something better comes out that is a clear solution. A curcumin analogue or a topical TGF-beta inhibitor developed by drug companies will be our best bet.

As for putting curcumin in a minoxidil solution, I don't know what the possibilities or the problems would be. You'd have to talk to an organic chemist. I took organic chemistry years ago, so it's not really all that fresh in my mind. In fact, if I never have to look at molecular structures again, I'd be a happy man.

 

[abcdefg]

my cousin is starting this year at university of michigan for masters in chemistry. He is taking physical chemistry. Im glad I dont have that crap who wants to do differential equations applied to chemistry? not me.

 

[michael barry]

spectral DNC has apple and grape proanthocyanidns in it (as well as minoxidil, aminexil, pirictone olamine, nanosomal capascium, nanosomal hops, nanosomal ivy extract)


the Revita shampoo has them also (apple and grape proanthocyandins) as well as 2% keto, caffeine, adenioside, taurine, cysteine, lyseine, emu oil, and a few other thingy's.


If the polyphenols work to inbibit TGF beta topically...................they might work.



I have a sneaky feeling apple cider vinegar works to some extent because its been used for hairloss for damned eons for 'some' reason. I have been piddling around with beer and green tea mixed topically on a pinky finger hair..........................and its stimulated growth over the other "control" pinky finger. This is the exact opposite of what I expected as I was hoping the catechins and hops would act as anti-androgens, but I guess not.

 

[bornthisway]

I have been piddling around with beer and green tea mixed topically on a pinky finger hair..........................and its stimulated growth over the other "control" pinky finger.

lol

 

[Beethoven]

Thanks for the reply Doctor!

 

[Bryan]

Beethoven, you'd probably be interested in reading the study "Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid", Liao et al, Arch Dermatol Res (2001) 293: 200-205.

They dissolved curcumin in ethanol and applied it to hamster flank organs. 1 mg curcumin in 5 ul (micro-liters) of alcohol. They measured an 87% decrease in the testosterone-stimulated growth of the organ (which was even a bit greater than what gamma-linolenic acid was able to do!). Interestingly, they also measured a 31% decrease in DHT-stimulated growth from the curcumin..

You might be interested to know that plain old EGCG (like from green tea) did better against DHT than curcumin did, with an astonishing inhibition of 97%!!

Bryan

 

[docj077]

Beethoven, you'd probably be interested in reading the study "Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid", Liao et al, Arch Dermatol Res (2001) 293: 200-205.

They dissolved curcumin in ethanol and applied it to hamster flank organs. 1 mg curcumin in 5 ul (micro-liters) of alcohol. They measured an 87% decrease in the testosterone-stimulated growth of the organ (which was even a bit greater than what gamma-linolenic acid was able to do!). Interestingly, they also measured a 31% decrease in DHT-stimulated growth from the curcumin..

You might be interested to know that plain old EGCG (like from green tea) did better against DHT than curcumin did, with an astonishing inhibition of 97%!!

Bryan

I wish I could figure out the mechanism of curcumin's decrease of testosterone stimulated growth. That would answer some questions for me.

 

[Old Baldy]

Doctor does this help?

1: J Med Chem. 2002 Nov 7;45(23):5037-42. Links
Antitumor agents. 217. Curcumin analogues as novel androgen receptor antagonists with potential as anti-prostate cancer agents.Ohtsu H, Xiao Z, Ishida J, Nagai M, Wang HK, Itokawa H, Su CY, Shih C, Chiang T, Chang E, Lee Y, Tsai MY, Chang C, Lee KH.
Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, 27599-7360, USA.

A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(methoxycarbonylmethoxy)phenyl]-1,4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated beta-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the beta-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17alpha-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.

PMID: 12408714 [PubMed - indexed for MEDLINE

 

[docj077]

Doctor does this help?

1: J Med Chem. 2002 Nov 7;45(23):5037-42. Links
Antitumor agents. 217. Curcumin analogues as novel androgen receptor antagonists with potential as anti-prostate cancer agents.Ohtsu H, Xiao Z, Ishida J, Nagai M, Wang HK, Itokawa H, Su CY, Shih C, Chiang T, Chang E, Lee Y, Tsai MY, Chang C, Lee KH.
Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, 27599-7360, USA.

A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(methoxycarbonylmethoxy)phenyl]-1,4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated beta-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the beta-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17alpha-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.

PMID: 12408714 [PubMed - indexed for MEDLINE

That helps a lot. Thank you.