Efficacy of an agonist of α-MSH, the palmitoyl tetrapeptide-20, in hair pigmentation.

OBJECTIVE: Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of α-melanocyte-stimulating hormone (α-MSH), a biomimetic peptide (palmitoyl tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying. METHODS: Effect of the PTP20 on the enzymatic activity of catalase and the production of H2 O2 by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor-1 (MC1-R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro-dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP-1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities. RESULTS: The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H2 O2 . Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was also observed. The pivotal role of MC1-R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide. CONCLUSION: The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α-MSH to promote hair pigmentation and thus, reduce the hair greying process.

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. OBJECTIVES: To identify biomarkers associated with AGA. METHODS: Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. RESULTS: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/ß-catenin and bone morphogenic protein/transforming growth factor-ß signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. CONCLUSIONS: This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.

N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED): a site-specific hydroxyl radical scavenger acting as an "oxidative stress activatable" iron chelator in vitro.

During oxidative stress, iron traces are supposed to be released from normal storage sites and to catalyse oxidative damage by Fenton-type reactions. This type of damage is difficult to prevent in vivo except by the use of strong iron chelators such as deferoxamine (affinity constant for Fe(III): log K = 30.8). However, strong iron chelating agents are also suspected to mobilize iron from various storage and transport proteins thereby leading to toxic effects. In contrast, N,N'-bis-dibenzyl ethylenediaminediacetic acid (DBED) is an iron chelator with relatively low affinity for iron (affinity constant for Fe(III): log K < 15). In the present paper, we show that, in situations mimicking oxidative stress in vitro, DBED is site-specifically oxidized into new species with strong iron binding capacity. Indeed, in the presence of ascorbate as a reductant, the iron chelate of DBED reacts with H2O2 in aqueous solution to yield a purple chromophore with minor release of free HO. in the medium, as measured by aromatic hydroxylation assay. The formation of these purple species is not suppressed by the presence of HO. scavengers at high concentration. The visible spectrum of these species is consistent with a charge transfer band from a phenolate ligand to iron. N-2-hydroxybenzyl N'-benzyl ethylenediaminediacetic acid (HBBED) was identified in the medium as one of the oxidation products of DBED. Therefore, these results suggest that the iron chelate of DBED undergoes an intramolecular aromatic hydroxylation by HO. leading to 2-OH derivatives and hence that DBED is a site-specific HO. scavenger. Moreover, since the measured affinity for Fe(III) of HBBED (log K = 28) is at least 13 orders of magnitude higher than that of DBED and since ferric HBBED chelate is not a catalyst of Fenton chemistry, DBED may be looked as an "oxidative stress activatable" iron chelator, e.g. which increase in affinity for iron is triggered in the presence of H2O2 and an electron donor. Therefore it is proposed that DBED and related derivatives may be interesting as protective compounds against oxygen radicals toxicity, especially for chronic use.

Synthesis of 2-N-oleoylamino-octadecane-1,3-diol: a new ceramide highly effective for the treatment of skin and hair.

Synopsis 2-N-Oleoylamino-octadecane-1,3-diol is a new synthetic ceramide. The process enables a four-step preparation of 2-amino-octadecane-1,3-diol (D,L-erythro/threo) and a five-step synthesis of 2-N-oleoylamino-octadecane-1,3-diol (D,L-erythro/threo). The latter compound is related to ceramide 2 according to the classification of Downing. This route of synthesis is rapid, reproducible and uses low-cost starting materials. The new ceramide was analysed as follows: (1)H, (13)C, (15)N NMR spectra afforded an unambiguous characterization of the structure; additionally, these three methods identified the threo and erythro isomers. (1)H and (13)C NMR permitted the measurement of the threo/erythro ratio (26.6/73.4 and 25.5/74.5, respectively). Chemical ionization mass spectrometry confirmed the expected mass of the pseudo-molecular ion (m/z= 566.5: [M + H](+)) as well as the presence of different chain lengths other than the oleic moiety due to the fatty acid composition of the technical grade oleic acid used for the synthesis. Capillary gas chromatography measured the threo/erythro ratio (23.5/76.5) which agrees with the (1)H and (13)C NMR data. Moreover, this method afforded the relative distribution of the different N-acylated chains. The properties of the new synthetic ceramide for the treatment of skin and hair were mainly assessed by two in vitro methods. The first measured the flux of water through lipid-extracted stratum corneum. The described ceramide showed high efficacy in decreasing water loss. The second recorded the friction coefficient of different types of hair: virgin, permanent-waved, and bleached. Treatment by the ceramide led to a strong decrease in this coefficient. This was particularly observed on unrinsed hair. These findings suggest two potential fields of application and beneficial contribution for the new ceramide: repairing the barrier to transepidermal water loss, and improving the surface properties of hair. Synthèse du 2-N-oleoylamino-octadécane-1,3-diol: nouveau céramide à haut potentiel dans le soin de la peau et du cheveu.

Antioxidant activity of flavonoids: efficiency of singlet oxygen (1 delta g) quenching.

Flavonoids, polyphenolic pigments widely present in plants, have been reported to act as scavengers of various oxidizing species. However, most often an overall antioxidant effect was measured. In this paper we report the results of a systematic study of the reactivity of 13 selected flavonoids (from the flavonol, flavone, flavanone and flavane families) with singlet oxygen (1O2(1 delta g)) in order to establish a structure-activity relationship. The rate constants of the chemical reaction of these flavonoids with 1O2(k r) and their rate constants of 1O2 physical quenching (kq) have been determined by kinetic measurements and near-IR singlet oxygen luminescence. The efficiency of the physical quenching is mainly controlled by the presence of a catechol moiety on ring B, whereas the structure of ring C (particularly the presence of a hydroxyl group activating the double bond) is the main factor determining the efficiency of the chemical reactivity of these compounds with 1O2. The total reactivity factor determining the efficiency of the chemical reactivity of these compounds with 1O2. The total reactivity scale is dominated by kq, which is in general higher than kr. (+)-Catechin is the most efficient quencher of the series.