This post is about a relatively older but still-interesting line of research linking the human hormone alpha-melanocyte-stimulating hormone (alpha-MSH) to reduction of inflammation. Melanocytes are cells which produce the pigment melanin which gives color to the skin, eyes and hair. In the blog post, More research insight on gray hair and adult stem cell reproduction I discussed how declining numbers of melanocyte stem cells is responsible for the hair of older people turning white or gray. Melanocytes are found in multiple body tissues in addition to hair follicles, including the skin, meninges, bone and heart. The role of alpha-MSH in activating activate melanocytes has been extensively studied for some time(ref)(ref)(ref). Alpha-MSH is produced in the pituitary gland, in neural cells, monocytes and certain types of skin cells. For example, consider suntan. When ultraviolet radiation impacts on keratinocytes, the keratinocytes release alpha-MSH. Melanocytes have target receptors for alpha-MSH and when alpha-MSH binds to skin melanocytes, they generates the black pigment eumelanin. The result is suntan. [Actually the situation is a bit more complicated than this since other factors are also involved in producing eumelanin and the melanocytes have other regulatory functions besides producing eumelanin(ref)(ref)(ref)(ref).]
With respect to theories of aging it is interesting that Alpha-MSH inhibits the expression of NF-kappaB and is a powerful anti-inflammatory, affecting what is possibly a key pathway in inflammatory pathologies(ref). “We report that alpha-melanocyte-stimulating hormone(10–9 M) was effective in opposing a tumor necrosis factor-
This is quite interesting since runaway expression on NF-kappaB and TNF-alpha seem to be characteristic of melanoma. Systemic administration of alpha-MSH appears to inhibit inflammation in general. For example, it has been shown to be capable of inhibiting colonic inflammation in inflammatory bowel disease, at least in rats(ref). It can inhibit edema in the mouse paw and acute ear inflammation in mice(ref). Another study description indicates “The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of pro-inflammatory mediators. Alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro(ref).” In the nervous system, the anti-inflammatory effects of alpha-MSH are communicated via neurogenic signaling. One report indicates “We recently found that alpha-MSH can act solely within the brain to inhibit inflammation caused by a general irritant applied to the skin. This activity appears to be shared with salicylate drugs and the combined observations suggest the existence of descending neurogenic anti-inflammatory signals capable of modulating inflammation in peripheral tissues(ref).”The way that alpha-MSH works to limit inflammation appears to be through inhibiting expression of NF-kappaB which is essential for the expression of proinflammatory cytokines. It appears to do this by prevention of degradation of IkappaBalpha, a protein that keeps NF-kappaB locked up in the cell cytoplasm and out of the nucleus(ref).
NF-kappaB plays a central role in the Programmed Epigenomic Changes theory of aging. There does not seem to be much current research action on the anti-inflammatory effects alpha-MSH or use of alpha-MSH as an anti-inflammatory therapy but I would not be surprised to see this thread picked up again at some point in an expanded context.
there is a drug which stimulates alpha-MSH in stage 3 clinicals that has actually been in development for over a decade.
Thanks. will look into it. Vince
“afamelanotide” is the generic name for melanotan-1.
There’s an interesting article on Wired Science about these peptides:
Also the Sun:
Prophets and melotan-afamelanotide:
This time you have got me really interested and I will look into afamelanotide and do a new post on this substance soon. I am interested in it from the personal viewpoint of protection against skin cancers (having recently found and have gotten rid of a basal cell carcinoma) and from the viewpoint of possibly turning age-related grey hair black. Funny, I started the process of preparing a new post on melanocytes yesterday, and this fits in perfectly. Thanks Vince
Melanotan-1 (generic name “afamelanotide”) has been approved for treatment of EPP in Italy. It will be sold under the Clinuvel owned trademark brand name “Scenesse”:
More info: http://melanotan.org/#Scenesse
Fascinating. Again, this is something I want to look into further.
I think there is going to be a rather large quantity of news about these latest developments over the next 12 to 24 months. This drug marks the first ever melanocortin peptide to have been approved as a medicinal drug by a governmental health regulatory body.
I will be on the lookout for such news.
Melanotan 1 is indeed an eye catching product. Even I believe that there is no harmful thing about melanotan.
I do not predict anything too exciting to come of Scenesse, but look forward to news stories on the subject.