Cyanidin 3-O-arabinoside suppresses DHT-induced dermal papilla cell senescence by modulating p38-dependent ER-mitochondria contacts

[badnewsbearer]

Cyanidin 3-O-arabinoside suppresses DHT-induced dermal papilla cell senescence by modulating p38-dependent ER-mitochondria contacts - Journal of Biomedical Science

Background Androgenetic alopecia (Androgenetic Alopecia) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs) located in the base of hair follicles. DHT causes DPC senescence in Androgenetic Alopecia through mitochondrial dysfunction. However...

jbiomedsci.biomedcentral.com

Abstract​

Background​

Androgenetic alopecia (Androgenetic Alopecia) is a genetic disorder caused by dihydrotestosterone (DHT), accompanied by the senescence of androgen-sensitive dermal papilla cells (DPCs) located in the base of hair follicles. DHT causes DPC senescence in Androgenetic Alopecia through mitochondrial dysfunction. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the protective role of cyanidins on DHT-induced mitochondrial dysfunction and DPC senescence and the regulatory mechanism involved.

Results​

Cyanidin 3-O-arabinoside (C3A) effectively decreased DHT-induced mtROS accumulation in DPCs, and C3A reversed the DHT-induced DPC senescence. Excessive mitochondrial calcium accumulation was blocked by C3A. C3A inhibited p38-mediated voltage-dependent anion channel 1 (VDAC1) expression that contributes to mitochondria-associated ER membrane (MAM) formation and transfer of calcium via VDAC1–IP3R1 interactions. DHT-induced MAM formation resulted in increase of DPC senescence. In Androgenetic Alopecia mice models, C3A restored DHT-induced hair growth deceleration, which activated hair follicle stem cell proliferation.

Conclusions​

C3A is a promising natural compound for Androgenetic Alopecia treatments against DHT-induced DPC senescence through reduction of MAM formation and mitochondrial dysfunction.

 

[badnewsbearer]

different pathways of androgen signaling are involved in Androgenetic Alopecia, genomic factors which are mediated through the androgen receptor as well as non genomic effects that are in this case for example mediated by membrane androgen receptors(those will not be blocked by an anti androgen like RU or pyrilutamide for example)

furthermore this drug which itself does not have any sexual side effects because it is not an actual anti androgen, can amorqeliate BOTH, the genomic pathways by translocation of the androgen receptor in dermal papilla cells as well as non genomic pathways which seems to be induction of oxidative stress, by being a powerful ROS scavenger and thus reducing DHT induced mitochondrial dysfunction.

this might lead to a connection of androgenic alopecia and age related hair loss(which is usually not patterned). basically, androgens increase oxidative stress and inflammation which leads to cellular scenencense. this can be characterized as cells losing their original function and much like old people they become senile and dont work properly anymore, get damaged and die. there is various studies suggesting scenencense in dermal papilla cells of old people but also in bald scalp. basically DHT among other things make the hair follicle reach the phenotype of an old man much faster in young men leading to dysfunction.

there is a community effort at HairDAO, a community funding for hair loss (what I wish this forum would be basically)
(who got Ralf Paus on board) to synthesize this molecule and preperare it in a stable formulation (bc it tends to be unstable or stable only for a week or so). they actually funded their first study with dr Paus on thyroid hormones for Androgenetic Alopecia. I think this project is fantastic
check out their pipeline for funding:

HairDAO - Project Pipeline

www.hairdao.xyz

I think anyone can participate. there is no in vivo data on this drug however the in vitro data on cultured DP cells looks extremely promising and it scientifically makes a lot of sense

videos of Dr Paus and HairDAO. he said "hair loss is not a cosmetically disease, its not cosmetic if it affects people mentally", he seems to get it. personally I think most people here know a lot about hair loss so maybe it could be worth checking out this community and making a contribution to fund something like this and other projects

 

[Armando Jose]

Wow, Mr, Paus has an advance common baldness, I meet him in 2004 in Berlin with more hair

 

[Baldingtooyoung]

The T3 and T4 study results come out in May? That's pretty cool if that's true

 

[badnewsbearer]

The T3 and T4 study results come out in May? That's pretty cool if that's true

yes they come in may