Retinoic Acid & Peppermint Oil possible mode of action

[mr_robot]

Retinoic Acid (Retin-A) and Peppermint Oil are well known and there has been much discussion about how they work and if they work at all. Retin-A is said to help minoxidil absorption whilst Peppermint Oil helps by acting as a vasodilator, my initial thoughts when researching was Retin-A helped due to its PTGDS inhibition and Peppermint Oil via Rosmarinic acid although I have to concede that the latter may not be the case when using peppermint essential oils.

However I now believe there is relation to IL-6. There was a study on IL-6 that has been touched on before http://www.hairlosstalk.com/interac...6-may-be-one-of-the-factors-involved-in-the-p

Re-quoting the study http://www.ncbi.nlm.nih.gov/pubmed/21881585

Autocrine and paracrine factors are produced by balding dermal papilla (DP) cells following dihydrotestosterone (DHT)-driven alterations and are believed to be key factors involved in male pattern baldness. Herein we report that the IL-6 is upregulated in balding DP cells compared with non-balding DP cells. IL-6 was upregulated 3  hours after 10-100  nM DHT treatment, and ELISA showed that IL-6 was secreted from balding DP cells in response to DHT. IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) were expressed in follicular keratinocytes, including matrix cells. Recombinant human IL-6 (rhIL-6) inhibited hair shaft elongation and suppressed proliferation of matrix cells in cultured human hair follicles. Moreover, rhIL-6 injection into the hypodermis of mice during anagen caused premature onset of catagen. Taken together, our data strongly suggest that DHT-inducible IL-6 inhibits hair growth as a paracrine mediator from the DP.

According to this IL-6 is elevated in the balding DP cells and adding DHT to DP cells causes IL-6 upregulation. rhIL-6 causes inhibited hair shaft elongation (miniaturization) therefore IL-6 is bad. This recent study (http://onlinelibrary.wiley.com/doi/10.1111/exd.12896/pdf) however suggests that IL-6 when present during wounding is good but I don't think these two observations of IL-6 are contradictory as:

IL-6 is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other tissue damage leading to inflammation.

It is plausible that IL-6 presence where there is no trauma is detrimental to hair follicles.

So what does this have to do with Retin-A and Peppermint Oil? I came across this study today: http://www.ncbi.nlm.nih.gov/pubmed/2033252

In this report we demonstrate that retinoic acid (RA) down-regulated the number of IL-6R on human leukocyte cell lines, including the myeloma cell line AF10, and two B cell hybridomas that correspond to cells at earlier stages of B cell development. Using AF10 cells, whose growth was determined to be mediated by the autocrine action of IL-6, we found that RA reduction of IL-6R was concentration-dependent over a range of 10(-11) to 10(-5) M and corresponded to the ability of the retinoid to inhibit cell proliferation. The down-regulation of IL-6R number by RA was accompanied by reduced IL-6R mRNA expression. RA did not affect endogeneous IL-6 synthesis or secretion from AF10 cells. However, addition of exogenous rIL-6 could overcome RA-induced growth inhibition. Menthol, a structurally unrelated compound to RA, also suppressed IL-6R expression and, correspondingly, inhibited cell growth. Taken together, our results suggest that the antiproliferative action of RA on AF10 cells is caused by reduction of IL-6R expression and subsequent inhibition of IL-6-mediated autocrine growth. These findings suggest the possibility that down-regulation of IL-6R is a means by which RA can modulate immune function.

It would seem that Retin-A down regulates the number of IL-6 receptors whilst Menthol (the bulk component of peppermint oil) suppresses IL-6 receptor expression. So we are basically inhibiting IL-6 by using these two which in the case of IL-6 produced by DHT attaching to DP cells is a good thing, however we will also inhibit IL-6 produced as a reaction to wounds which is a bad thing. The other consideration is that there are limits to how much Retin-A and Methol can be applied to skin and as such it may be the limiting factor for both, although without a proper study it is impossible to know.

Additionally there is also a link between Vitamin E and IL-6 due to its anti inflammatory properties which may be worth looking into.

 

[mr_robot]

Not sure what the relation is between the article and hair. It's a good article, but it's about the
immunity system.

The article is about IL-6R inhibition via RA and Menthol. IL-6R is present in the hair follicle, inhibiting it means the IL-6 produced by DHT is no longer harmful. This is blocking the effect of DHT but further down the chain, so no need for an AA like finasteride, RU, etc.