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JAK inhibitors - INCREDIBLE hair growth

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JAK inhibitors - INCREDIBLE hair growth

Post  Changexpert on Mon Oct 26, 2015 8:31 am

This experimental success for hair was an accidental finding, which was confirmed by a rat study recently. The idea of inhibiting JAK pathway stems from a theory that hair loss is caused by autoimmune response creating unnecessary inflammation.

http://www.belgraviacentre.com/blog/treating-alopecia-universalis-with-arthritis-drug-xeljanz-may-have-serious-side-effects/
http://www.nbcnews.com/health/health-news/cancer-drug-could-be-baldness-remedy-too-n450256

The difference among JAK1, 2, and 3 is really subtle, as all of them are involved in many pathways as shown in the diagram attached below.

A diagram that shows differecne among different JAK (1,2,3) pathways
http://www.ebioscien...tat-pathway.jpg

I think inhibiting JAK-2 is not as beneficial because it will result in HGH inhibition, but that's just my guess.

JAK1 - Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor

JAK2 - Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.

JAK 3 - Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.

Source: http://www.uniprot.org/uniprot/P52333

Although this is the most promising substance I've ever seen for hair loss, I I am concerned about long-term effect of immune system suppression. I do not think taking a JAK inhibitor permanently is a good idea as it has a great potential to alter immune system. Any thoughts on this?
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  rofl on Mon Oct 26, 2015 2:29 pm

i agree  its not a good solution even if it works good), but if the dose response curve is not steep, and they can find the therapeutic window between hair regrowth and too much immune system inhibition, then maybe its a viable treatment.

i actually think thats also the answer to the finasteride problem. change the dose response curve so that a more exact dose can be used to find the line between efficacy and side effects. at the moment .2 mg is too little (not very effective) and .1 is too much(side effects) but the steep incline in the curve means doses in between are either one or the other, and the point in between is too hard to accurately measure.
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  CausticSymmetry on Wed Oct 28, 2015 3:46 am

The problem with these drugs that they have a tendency to increase the chance of death.

The "autoimmune component" is usually related to gut motility and digestion.  Shutting off this immune regulation just ignores the real problem.

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  johndoe1225 on Wed Oct 28, 2015 4:11 am

CausticSymmetry wrote:The problem with these drugs that they have a tendency to increase the chance of death.

The "autoimmune component" is usually related to gut motility and digestion.  Shutting off this immune regulation just ignores the real problem.

I read something about JAK on MPB-research involving Resveratrol/Curcumin?

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  invinoveritas on Wed Oct 28, 2015 5:58 am

This article talks about the JAK/STAT signaling pathway targeted by natural inhibitors such as Thymoquinone (Nigella Sativa) and Capsaicin (Chili Pepper)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316753/

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  CausticSymmetry on Wed Oct 28, 2015 6:42 am

invinoveritas wrote:This article talks about the JAK/STAT signaling pathway targeted by natural inhibitors such as Thymoquinone (Nigella Sativa) and Capsaicin (Chili Pepper)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316753/

Bravo!

Nigella Sativa is a good one, and then there is Scutellaria baicalensis mentioned on this thread.

http://immortalhair.forumandco.com/t9931-the-inhibitory-effect-of-scutellaria-baicalensis-extract-and-its-active-compound-baicalin-on-the-translocation-of-the-androgen-receptor-with-implications-for-preventing-androgenetic-alopecia

Capsaicin does to be a problem if too much is used.

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  Changexpert on Wed Oct 28, 2015 6:58 am

I agree with CS. Capsaicin from peppers initiates TRPV1 pathway which ultimately increases TGF-B. I used to love spicy food, but now I try to stay away from them because my scalp itches so much after eating it these days.
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  invinoveritas on Wed Oct 28, 2015 1:46 pm

Sounds like we could benefit from topical application of nigella sativa as YAER has been advising in the past.

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  4039 on Wed Oct 28, 2015 2:16 pm

Shutting down your immune system to grow hair is as incredible shortsighted as leaving your home wide open and insecure in a high crime neighborhood. And all because you were too lazy to shut the door. I actually feel bad for anyone desperate enough to play roulette with their lives and longevity.

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  invinoveritas on Wed Oct 28, 2015 4:00 pm

Nigella Sativa has been traditionally used by folk cultures to support the immune system function.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642442/
http://www.google.com/patents/US5482711

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  TNT on Wed Oct 28, 2015 6:44 pm

CS,Scutellaria baicalensis will be better internal or external?

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  RAptor on Wed Oct 28, 2015 9:41 pm

great news indeed, for mice
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  Changexpert on Thu Oct 29, 2015 12:26 am

The point of rat study was to prove that topical JAK inhibition can also lead to hair growth. There is no mentioning of whether topical application of Xeljanz can have a systematic impact or not, but hopefully it stays localized on the spot that's applied.
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  Columbo on Thu Oct 29, 2015 3:27 am

Nigella Sativa sounds like wonderful stuff!

"There is more, to Nigella sativa, but I am tired of listing all the references to its beneficial gastropotective effects, its ability to protect the kidneys and the liver from damage, its anti-stress and anti-anxiety effects, its beneficial effects against candida, bacterial infections and fungi, or its use as a post-coital contraceptive (acute high dose) and fertility booster (chronic low dose | Al-Sa'aidi. 2009) in females & males, respectively. If you want all the details, I suggest the review by Paarakh from 2010 or asking your local oriental medicine practitioner ;-). "

http://suppversity.blogspot.de/2015/01/reader-question-are-black-seeds-nigella.html

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  bl4cksun on Thu Oct 29, 2015 4:50 am

Hey !
I wondered if the oil of nigella sativa first cold pressing could be interesting too or the study mentioned only seeds ?
I am sorry, i don't speak well english.
Thank you

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  CausticSymmetry on Thu Oct 29, 2015 5:24 am

TNT wrote:CS,Scutellaria baicalensis will be better internal or external?

Internally - http://www.iherb.com/Dragon-Herbs-Standardized-Scute-500-mg-Each-100-Veggie-Caps/55598

Note on the Nigella Sativa (Do not take the oil)

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  TNT on Thu Oct 29, 2015 5:29 am

Thx CS,
what do you mean not take the oil of nigella sativa? It's good for topical use, right?

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  CausticSymmetry on Thu Oct 29, 2015 5:44 am

TNT wrote:Thx CS,
what do you mean not take the oil of nigella sativa? It's good for topical use, right?

The oil doesn't have all of the good stuff that the seeds do. and the worst part is that the oil itself is high in pro-inflammatory omega-6...I speak from experience trying only the oil.

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  TNT on Thu Oct 29, 2015 6:11 am

Crying or Very sad i have already order this one

http://www.ebay.com/itm/The-Strongest-Organic-Black-Seed-Oil-Nigella-Sativa-Cumin-Kalonji-cold-pressed-/181906094720?hash=item2a5a72ba80:g:TvQAAOSwuTxV8YWs

can i use it just topical?

I will order some seeds too

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  Changexpert on Thu Oct 29, 2015 11:57 am

CausticSymmetry wrote:the worst part is that the oil itself is high in pro-inflammatory omega-6...I speak from experience trying only the oil.
Do you have studies for this CS? In which pathways does omega-6 (PUFA) work to cause inflammation? Is it PGD2? TRPV1? Or some other pathways?
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  CausticSymmetry on Thu Oct 29, 2015 1:31 pm

Changexpert wrote:
CausticSymmetry wrote:the worst part is that the oil itself is high in pro-inflammatory omega-6...I speak from experience trying only the oil.
Do you have studies for this CS? In which pathways does omega-6 (PUFA) work to cause inflammation? Is it PGD2? TRPV1? Or some other pathways?

Linoleic acid 55.6%


http://www.probotanic.com/pdf_istrazivanja/crni_kumin/Hemijski%20sastav%20ulja%20crnog%20kumina.pdf

Prostaglandins Leukot Med. 1985 Mar;17(3):319-27.
Docosahexaenoic acid (C22:6 omega 3) and linoleic acid are anti-aggregatory, and alter arachidonic acid metabolism in human platelets.
Srivastava KC.

Effects of various concentrations (12.5-500 uM) of linoleic acid and docosahexaenoic acid (C22:6 omega 3)(sod. salt) were examined on the platelet metabolism of labelled arachidonate (AA) under two different incubation conditions. In the first platelets were pretreated with either fatty acid prior to incubation with labelled AA; and in the second incubation platelets were incubated with a mixture containing a fatty acid (linoleic acid or DHA) and labelled AA. At all concentrations the two fatty acids reduced the formation of TxB2. At lower concentrations (up to 200 uM) the fatty acids inhibited platelet cyclooxygenase as shown by a reduced formation of prostaglandins (PGs) and TxB2. At higher concentrations (400 and 500 uM), however, the fatty acids behaved differently. Although TxB2 formation was reduced, there was observed an increased formation of PGs. In DHA pretreated platelets only PGE2 increased (to double control values). Platelets pretreated with linoleic acid produced increased amounts of all PGs (PGF2 alpha, PGE2, PGD2), and this effect was greatest for PGE2 which increased by 5-6 fold of control values. DHA showed a dose-dependent inhibition of platelet aggregation induced by arachidonate, epinephrine and collagen.

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  Changexpert on Thu Oct 29, 2015 11:17 pm

CausticSymmetry wrote:
Changexpert wrote:
CausticSymmetry wrote:the worst part is that the oil itself is high in pro-inflammatory omega-6...I speak from experience trying only the oil.
Do you have studies for this CS? In which pathways does omega-6 (PUFA) work to cause inflammation? Is it PGD2? TRPV1? Or some other pathways?

Linoleic acid 55.6%


http://www.probotanic.com/pdf_istrazivanja/crni_kumin/Hemijski%20sastav%20ulja%20crnog%20kumina.pdf

Prostaglandins Leukot Med. 1985 Mar;17(3):319-27.
Docosahexaenoic acid (C22:6 omega 3) and linoleic acid are anti-aggregatory, and alter arachidonic acid metabolism in human platelets.
Srivastava KC.

Effects of various concentrations (12.5-500 uM) of linoleic acid and docosahexaenoic acid (C22:6 omega 3)(sod. salt) were examined on the platelet metabolism of labelled arachidonate (AA) under two different incubation conditions. In the first platelets were pretreated with either fatty acid prior to incubation with labelled AA; and in the second incubation platelets were incubated with a mixture containing a fatty acid (linoleic acid or DHA) and labelled AA. At all concentrations the two fatty acids reduced the formation of TxB2. At lower concentrations (up to 200 uM) the fatty acids inhibited platelet cyclooxygenase as shown by a reduced formation of prostaglandins (PGs) and TxB2. At higher concentrations (400 and 500 uM), however, the fatty acids behaved differently. Although TxB2 formation was reduced, there was observed an increased formation of PGs. In DHA pretreated platelets only PGE2 increased (to double control values). Platelets pretreated with linoleic acid produced increased amounts of all PGs (PGF2 alpha, PGE2, PGD2), and this effect was greatest for PGE2 which increased by 5-6 fold of control values. DHA showed a dose-dependent inhibition of platelet aggregation induced by arachidonate, epinephrine and collagen.
So is it just LA that causes this inflammation or does all omega 6 cause this? I ask this because every time I tried oil topicals that contain high omega 6 content like hemp seed oil, my hair shedded massively and looked very thin.
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  Changexpert on Thu Oct 29, 2015 11:24 pm

Has anybody tried Brevilin A? It inhibits JAK. Brevilin A is an extract from a herb called Litsea Glutinosa. I doubt long-term ingestion would be good due to a potential of altered/suppressed immune system. Maybe topical would work well. There is a lotion/topical from India that contains Litsea Glutinosa. I might give that a try and apply that on balding areas.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063697
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038293/
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Re: JAK inhibitors - INCREDIBLE hair growth

Post  invinoveritas on Fri Oct 30, 2015 2:49 am

User AnteUp from another forum is reporting some success with Litsea Glutinosa:
http://www.hairlosstalk.com/interact/showthread.php/88341-Androgenetic-Alopecia-Pathway-Update-and-Possible-Cure/page3

As for nigella sativa, would there be a difference using the seeds vs oil in terms regarding omega-6?

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Re: JAK inhibitors - INCREDIBLE hair growth

Post  CausticSymmetry on Fri Oct 30, 2015 3:16 am

invinoveritas - Yes, would stick to the seed extract instead of the oil.

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