Topically applied diacylglycerols increase pigmentation in guinea pig skin.
Abstract Exposure of human and murine melanocytes in vitro to the diacylglycerol (DAG) 1-oleoyl-2-acetyl-sn-glycerol (OAG) markedly increases melanin production within 24 h. To determine whether OAG can increase melanin production in vivo, increasing concentrations of OAG (10-60 mg/ml) in propylene glycol were applied daily for 5 d to shaved guinea pigs. Dose-dependent increased pigmentation was visible first on days 17-22 and persisted for 10-14 weeks. Peak epidermal melanin content in OAG-treated sites was more than twice that of untreated or vehicle-treated sites, as assessed by computerized image analysis of Fontana-Masson stained biopsy cross sections. In another experiment to assess the mechanism of DAG-mediated pigmentation, guinea pigs received twice daily separate applications of OAG, dipalmitoylglycerol (diC16), dioctanoylglycerol (diC8), each 50 mg/ml, 20 microliters/application, and propylene glycol vehicle alone for 5 d. Increased pigmentation was visible after 10 d in the OAG and diC8 sites but not in diC16 or vehicle sites. These results correlate with the reported ability of these compounds to activate protein kinase C in vitro. In a final experiment, guinea pigs received OAG 25 mg/ml three times daily to one test site, and once daily ultraviolet B (70 mJ/cm2, equivalent to 0.6 minimal erythemal dose) radiation to another for 10 d. The OAG and ultraviolet B test sites developed comparable pigmentation by both clinical and histologic criteria. Our data demonstrate that topically applied DAGs can produce a long-lasting increase in epidermal pigmentation, presumably through protein kinase C activation, which clinically and histologically closely resembles ultraviolet-induced tanning.
UV-induced increased melanogenesis is the major recognized protective response of human skin against subsequent photodamage, at least in part because of the ability of melanin to absorb damaging photons that otherwise target DNA and among its other protective responses in skin that contains epidermal melanocytes pTT causes tanning that is histologically identical to UV-induced tanning and highly photoprotective.* Inducible DNA repair was first recognized in bacteria. This so-called SOS response (41) is initiated by partially processed damaged DNA and mediated by transcriptional up-regulation of genes encoding DNA repair enzymes. Interestingly, several recent reports have suggested that NER is also inducible in mammalian cells. For example, carcinogen treatment (42) and low-dose UV irradiation (43, 44) enhance the repair rate for subsequent DNA damage in repair-proficient as well as repair-deficient mammalian cells. We have shown that pTT and other DNA oligonucleotides partially or totally homologous to the 3? telomere overhang also induce protective effects (12, 13, 17, 22, 23, 27, 28), presumably by mimicking a physiologic signal generated during the course of DNA damage or its repair (17, 23), and in any case mimicking the cellular response to telomere loop disruption and overhang exposure (23, 27, 28), a presumptive DNA damage signal (26).
Our findings suggest that telomere-based inducible DNA damage responses are important mechanisms by which cells manage recurrent DNA insults throughout life. Our data further suggest that topically applied pTT may enhance DNA repair capacity in human skin, in the absence of actual DNA damage that normally induces this protective response (17, 23), and may thus reduce the carcinogenic risk from subsequent solar UV irradiation in individuals at high risk because of fair skin, other genetic predisposition, or advanced age.
well you know, there are many patents online theses days, some are very promising. But as this is a melanotan website, I don't know if you really want me to elaborate on it. Don't wanna cause any trouble*
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well you know, there are many patents online theses days, some are very promising. But as this is a melanotan website, I don't know if you really want me to elaborate on it. Don't wanna cause any trouble* ]"
Absolutely of interest to viewers here, post away!* Is there anything in particular that has your attention JustinBee?
BACKGROUND
The melanocortins include a family of peptide hormones that induce pigmentation by interaction with melanocortin-1 receptors (MC1R) in the epidermis. The primary pigmentary hormone that is released from the pars intermedia of the pituitary gland in some non-human animals, and from UV exposed keratinocytes in human skin, is alpha melanocyte stimulating hormone (alpha-MSH). This 13 amino acid peptide binds to MC1R to induce cyclic AMP-mediated signal transduction, which leads to the synthesis of melanin polymers from DOPA precursors. Two types of melanins can be expressed in humans. The brownish-black pigment eumelanin is believed to convey protection from sun damage, whereas the reddish, sulfur-containing pigment, pheomelanin, is often expressed in light-skinned human populations that report a poor tanning response to sunlight. These poorly-tanning, easily-burning populations often possess defects in the MC gene and are generally thought to be at a greater risk of developing both melanoma and non-melanoma skin cancers.
It has previously been disclosed that a super-potent derivative of alpha-MSH, Melanotan (Nle4-D-Phe7-alpha MSH, also referred to herein as “Melanotan-1” or “MT1”), can induce tanning in human volunteers. Melanotan is approximately 100 to 1,000-fold more potent than the native hormone at inducing pigmentation in human keratinocytes. In humans, Melanotan primarily induces eumelanin synthesis in the skin in concert with its tanning effect. Although melanotropins have been postulated to affect immunologic changes, all of the prior trials reported only minimal side effects such as facial flushing and transient GI upset, unless doses greater than those needed for tanning were administered.
There is compelling evidence that melanotropic peptides may provide a potential for increasing melanin pigmentation of human skin. Synthetic MSH may be used to enhance skin pigmentation of normal or light-skinned individuals to protect them from the hazards of solar radiation. Several studies have suggested that individuals whose skin tends to burn easily on exposure to the sun and does not tan readily are at higher risk of both nonmelanoma skin tumors and of cutaneous melanoma. There is unambiguous evidence that UV radiation is responsible for skin cancer in humans. In the face of increased deterioration of the ozone layer and the increasing incidence of and mortality from skin cancer, the ability to stimulate the skin's own “protective mechanism” of tanning may prove extremely important as photoprotective strategy.
Accordingly, described herein are compositions and methods for inducing melanogenesis in a human subject by topically administering alpha-MSH analogues to the subject which surprisingly leads to increased melanin density levels in the subject. By increasing melanin levels in a subject, it is possible to reduce or prevent the occurrence of UV radiation-induced skin damage in the subject.
SUMMARY
Described herein are compositions and methods for inducing melanogenesis in a subject. The advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the aspects described below. The advantages described below will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive.
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