Peptide Ac 2 Rescues Dht (dihydrotestosterone)-treated Human Dermal Papilla Cells

whatevr

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https://www.ncbi.nlm.nih.gov/pubmed/31729428

Abstract
The Trapa japonica fruit is a natural plant growing in ponds with its roots in the mud. It has long been used as a home remedy for many diseases; however, a major problem with this kind of natural extract is the multicomponents-multitargets for diseases. Such problems make it difficult to identify the mechanism of action. Another problem is quality control and consistency. The aim of this research was to isolate a single bioactive compound (peptide) derived from the Trapa japonica fruit. The research was conducted with various experimental techniques, such as fermentation and liquid chromatography, to isolate a peptide. We isolated the AC 2 peptide from Trapa japonica fruit and found it to be promising on human dermal papilla cells. Dihydrotestosterone (DHT) stresses human dermal papilla cells and is a major cause of hair loss resulting from hormones and environmental factors. The purpose of this research was to develop an understanding of the mechanism by which the AC 2 peptide rescues dihydrotestosterone (DHT)-treated human dermal papilla cells. We explored the effects of the AC 2 peptide on the cell biological functions of human dermal papilla cells (HDPs). HDPs were treated with the AC 2 peptide and DHT. Then, a cytotoxicity assay, flow cytometry, Western blot, immunoprecipitation, and 3D cell culture for immunohistochemistry were conducted to investigate the mTORC1 pathway and suppression of autophagy and apoptosis. In addition, we also synthesized the AC2 peptide as an alternative to the expensive and difficult isolation and purification procedures and confirmed its potential in biomedical applications. We also validated the effects of the synthetic AC2 peptide as well as the isolated and purified AC2 peptide and established their similarity. Although extensive research has been carried out on natural extracts, few single studies have isolated and separated a bioactive peptide (single compound).
 

whatevr

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OK, I want to point out why this is somewhat of a big deal.

There was a really important study recently which showed that VEGF peptide alone could very significantly mitigate a good deal of the damage induced by DHT, including SAVE CD200 and CD34 progenitor cells which have been proven to be deficient in bald men years ago by Garza and Cotsarelis. Let's put the pieces together:

1)https://www.ncbi.nlm.nih.gov/pubmed/21206086
Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.

2)https://www.ncbi.nlm.nih.gov/pubmed/31478937
Vascular Endothelial Growth Factor Protects CD200-Rich and CD34-Positive Hair Follicle Stem Cells Against Androgen-Induced Apoptosis Through the Phosphoinositide 3-Kinase/Akt Pathway in Patients With Androgenic Alopecia

VEGF is HUGELY important for hair growth and it's loss is probably one of the top reasons for the destruction of hair as it is responsible for vascularization of the DP and many other imporant hair growth mechanisms...Sadly it is very expensive to synthesize so buying it and applying externally is probably not an option (it's also implicated in cancer) so ideally we would want to identify the pathway where DHT sabotages VEGF and inhibit it in the hair follicle to restore normal VEGF levels.

Now the study in the OP showed that this AC2 peptide could save DP's from DHT damage via the mTORC pathway so I googled to find if the mTORC pathway had any crossover with VEGF, and here it is:

3)https://www.ncbi.nlm.nih.gov/pubmed/27458160
"upregulation of AP-1 or mTOR increased cell proliferation, and VEGF overexpression increased"
https://www.ncbi.nlm.nih.gov/pubmed/22144946
"Numerous inhibitors targeting the PI3K/AKT/mTOR pathway have been developed, and these agents have been shown to decrease VEGF secretion and angiogenesis."
https://cancerres.aacrjournals.org/content/68/9_Supplement/289
"Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A driven angiogenesis in part through the blockade of S6Kinase"

It seems plausible that inhibiting mTOR leads to a downregulation of VEGF and a whole host of negative effects on the DP, so if what this peptide does is to prevent negative effects of DHT on mTOR it could restore angiogenesis leading to the DP becoming revascularized and growing a much healthier and thicker hair once again. Currently the exact mechanism of how loss of VEGF happens downstream of AR is not known but it is hugely important and would be a big step forward if we could inhibit this pathway.

Some potential mechanisms are in the OP study:
"DHT treatment induces the cleavage of mTORC1 (mTOR-raptor interaction), initiating apoptosis and autophagy in the mitochondria and membranes of cells. "

"The AC2 peptide rescued human dermal papilla cells from DHT-induced stress by strengthening mTOR-raptor interactions and inhibiting autophagy and apoptosis."
 
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INT

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Interesting find, thanks.

Unfortunately not something we can 'do anything with' though..
 

AndrewU

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so do you suggest application of this peptide topically? If so what is the ease of either extracting, obtaining or synthesising this peptide?
 

whatevr

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Interesting find, thanks.

Unfortunately not something we can 'do anything with' though..

Not unless we can get a peptide lab to custom synthesize it for us... though we would need a lot of people interested.

so do you suggest application of this peptide topically? If so what is the ease of either extracting, obtaining or synthesising this peptide?

I was hoping there would be a ready-made extract of this plant that you could buy... but it seems there isn't. You would have to buy it (or the fruit), ferment it, then do a hot-water extract which yields a decent amount of the peptide as per the study. Pain in the *** regardless.
 
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