Roger Rozot

Expression of NAD+ dependent 15-hydroxyprostaglandin dehydrogenase and protection of prostaglandins in human hair follicle

Abstract:  NAD+ dependent 15‐hydroxyprostaglandin dehydrogenate (15‐PGDH) catalyses oxidation of 15(S)‐hydroxyl group of prostaglandins and as a result inactivates their physiological potential. Positive effects of prostaglandins or prostaglandin analogues were reported on terminal hair, vellus hair or eyelash growth and a complex prostaglandin network was recently described in human hair follicle. In the present study, we showed that 15‐PGDH was expressed in human hair follicle mainly in melanocytes and keratinocytes, which brought us to consider this enzyme as a possible target to sustain local prostaglandin production. Using a recombinant enzymatic strategy, specific 15‐PGDH inhibitors were screened. We identified a thiazolidine dione derivative exhibiting efficacy on follicular outer root sheath keratinocytes, since it concomitantly decreased the production of deactivated 13,14 dihydro 15‐ketoprostaglandin F2α and sustained prostaglandin F2αin vitro production. In the context of recent interest in prostaglandins and prostaglandin analogues as hair regrowth agents, we postulated that the use of selected 15‐PGDH inhibitors could reinforce or prolong the effect of these physiological mediators on hair and skin.

Fragment pharmacophore-based in silico screening: a powerful approach for efficient lead discovery

Through a process of fragmentation, functionalization, and recombination of market approved molecules for cosmetic usage, we customized an in-house virtual library comprising molecules ideally suited for virtual screening. Computational pharmacophore-based screening of this virtual library followed by a 3 month optimization phase led to the identification of an optimized lead with all its expected properties in hand to be developed as a candidate molecule for skin care in cosmetic applications. The success of this pilot project paves the way for other cosmetic targets of interest.

6-O glucose linoleate supports in vitro human hair growth and lipid synthesis

The hair follicle is a very active organ with a complex structure, which produces a hair fibre at a rate of 0.3 mm a day. Accordingly, the hair follicle is highly demanding in energy source, as the hair bulb matrix cells are endowed with one of the highest rates of proliferation in the human body. Moreover, recent data have shown the involvement of lipids in hair follicle function. As in vitro‐grown hair follicle keeps producing a hair fibre that closely resembles the natural hair fibre, we decided to use this model to investigate the role of a new of glucose linoleate derivative (6‐O‐linoleyl‐d‐glucose: 6‐O‐GL) as a lipid precursor and energy provider. Our results demonstrated that 6‐O‐GL was (i) quite stable and surprisingly resistant to oxidative degradation, and (ii) readily taken up and metabolized by the hair follicle into various lipids, namely neutral lipids, ceramides and polar lipids. Moreover, it supported hair follicle growth and survival in a glucose‐ and linoleic‐acid free medium. 6‐O‐GL thus appeared to be a bi‐functional nutrient, ensuring both proper fibre quality and production by the hair follicle.