A combination of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol stabilizes hypoxia-inducible factor 1-alpha and improves hair density in female volunteers.

OBJECTIVE: The aim of this study was first to demonstrate that a combination of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol could synergize in vitro on biological pathways associated with hair growth and then to demonstrate the benefit on hair density in a clinical study. METHODS: The effects of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol directly on the hypoxic inducible factor-1α protein (HIF-1α) and related genes expression were demonstrated on keratinocytes in culture in vitro using western-blot analysis and real time quantitative polymerase chain reaction analysis. The effect of resveratrol against oxidative stress induced by hydrogen peroxide treatment was studied in hair follicle and hair matrix cells in vitro using the sensitive probe Dichloro-dihydro-fluorescein diacetate (DCFH-DA). Finally, a randomized clinical study on hair density was conducted on 79 Caucasian female subjects to assess the effect of this combination of actives. RESULTS: Pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol stabilized HIF-1a protein and increased the expression of HIF-1α target genes. Resveratrol significantly reduced the oxygen peroxide-induced oxidative stress generated in hair follicle and hair matrix cells. The clinical study showed that a topical treatment with the combination significantly increased the hair density on women from 1.5 months. CONCLUSION: In addition to the antioxidant properties of resveratrol, the association of pyridine-2, 4-dicarboxylic acid diethyl ester and resveratrol revealed a synergistic effect on the HIF-1α pathway. The results of the clinical study confirmed the importance of such a combination to increase the hair density.

L'alopécie peut affecter 50% des femmes au cours de leur vie ce qui induit une perte de leur estime de soi et une diminution de leur qualité de vie. Au-delà des solutions chirurgicales et des traitements pouvant induire des effets secondaires potentiellement dangereux, il y a un besoin d'améliorer l'efficacité des produits cosmétiques qui permettent de prévenir la chute des cheveux tout en préservant la sécurité des patients. Ainsi, nous avons sélectionné une combinaison de pyridine-2, 4-dicarboxylic acide diethyle ester et de resvératrol pour activer des voies biologiques associées à la croissance du cheveu. Nous avons d'abord montré, in vitro, que la combinaison de pyridine-2, 4-dicarboxylic acide diethyle ester et de resvératrol permet de stabiliser la protéine HIF-1α conduisant ainsi à un effet synergique sur l'expression de gènes clés de la voie HIF-1α. Nous avons aussi démontré, in vitro, que le resvératrol permet de protéger significativement les follicules pileux et les cellules de la matrice du stress oxydatif induit par traitement au peroxide d'hydrogène. En final, une étude clinique randomisée mesurant la densité capillaire a été réalisée sur 79 femmes caucasiennes. Cette étude montre qu'une application topique d'une solution contenant de 5% pyridine-2, 4-dicarboxylic acide diethyle ester et 0.25% de resvératrol augmentent significativement la densité capillaire chez les femmes après 1.5 mois. En conclusion, ces résultats démontrent l'intérêt de stimuler la voie HIF-1α tout en protégeant les cheveux et le scalp du stress oxydatif afin d'améliorer la croissance des cheveux chez les femmes.

Non-invasive short-term assessment of retinoids effects on human skin in vivo using multiphoton microscopy.

BACKGROUND: The occlusive patch test developed for assessing topical retinoids activity in human skin has been extended as a short-term screening protocol for anti-ageing agents. In this model, biopsies are performed at the end of the occlusion period for morphological and immuno-histochemistry analysis. Multiphoton microscopy is a recent non-invasive imaging technique that combined with image processing tools allows the in vivo quantification of human skin modifications. OBJECTIVE: To validate with gold standards of anti-ageing that are retinoids, the relevance of multiphoton microscopy for kinetic and quantitative assessment in this model. METHODS: Twenty women, aged 50-65 years, were enrolled. Retinol 0.3% (RO) and Retinoic acid 0.025% (RA) were applied to the dorsal photo-damaged side of their forearm under occlusive patches for 12 days. A patch alone was applied to a third area as control. Evaluation was performed at day D0, D12 (end of treatment), D18 and D32 using multiphoton microscopy. Epidermal thickness, normalized area of the dermal-epidermal junction (DEJ) and melanin density were estimated using 3D image processing tools. RESULTS: Main significant results are: Epidermal thickening at D12, D18 and D32 with RO and at D12, D18 with RA vs. baseline and vs. CONTROL: Increased DEJ undulation at D32 with RO and at D12 with RA vs. baseline and vs. CONTROL: Decreased melanin content with RO (at D12 and D18 vs. baseline and at D32 vs. baseline and vs. control) and with RA (at D12 vs. baseline). CONCLUSIONS: This study shows that multiphoton microscopy associated to specific 3D image processing tools allows cutaneous effects induced by topical retinoids in this in vivo model to be non-invasively detected, quantified and followed over time. This innovative approach could be applied to the evaluation of other active compounds.