Hair follicles are impacted by external and internal stress factors such as UV, pollution, chemicals, cigarette smoke and psycho-emotional stress. One of the most visible sign of hair ageing is hair whitening, also known as canities. Thanks to very recent studies as well as our very own work, we demonstrated that this hair disorder is mainly caused by a strong impact of oxidative stress that was barely known until now. It is indeed the initial and disrupted factor which alters the biological pathways involved in hair pigmentation. 
In these works, we demonstrated that oxidative stress negatively regulated oxidative defences and renewal process as observed by a reduction of the expression of various key proteins through a proteomic analysis on hair scalp explants. We evidenced a strong impact of oxidative stress on melanogenesis and melanosome transport as demonstrated by the inhibition of MITF, DKK1, TYR but also SLC24A5, MLPH and MYO5A, respectively.  
Finally on human hair follicles, we observed a significant reduction in the number of melanoblasts and active melanocytes after exposure to oxidative stress. 
In this context, we designed a smart active compound which is a complex mixture between two main components: taxifolin glucoside, allowing protection and maintenance of stem cells thanks to its strong antioxidant properties; and N-acetyl tyrosine, a precursor of the melanin synthesis. We demonstrated that in presence of this active compound, the antioxidant defences and the expression of the main actors of the melanogenesis pathway were restored. 
Subsequently, we observed that the active compound protected from ROS accumulation induced by oxidative stress by +53%, also being an efficient protection against melanoblast apoptosis in hair follicles, with a difference of +189% in comparison with oxidative stress condition. Thanks to a gene expression analysis on stem cells from the Outer Root Sheath (ORS) of the hair follicles; we determined that the active compound stimulated the expression of genes involved in proliferation, hair follicle morphogenesis and stem cell maintenance. As a result, we confirmed an increase of proliferation of ORS stem cells using BrdU incorporation analysis. Finally, thanks to all these effects, we showed that the active compound was able to increase the melanin content in a co-culture model of NHEKs and NHMs, and to significantly reactivate pigmentation in white hair follicles. The efficacy was then confirmed at the in vivo level on a panel of volunteers presenting a proportion of 30 to 90% white hair. After 4 months of daily application, we evidenced a reduction of 17% compared to Day 0 with 2.1 times more efficacy than the placebo. We also observed a reduction of the number of white hair per cm2 by 6.8 relative to Day 0, which was 3.4 times more efficient than the placebo. 
In conclusion, we clearly evidenced that oxidative stress is a key factor that triggers a cascade of events leading to a loss of hair pigmentation. To tackle this phenomenon, we developed this effective active compound able to restore all the disrupted mechanisms and offering hair repigmentation in only 4 months.

Global repigmentation strategy of white hair follicles by targeting oxidative stress and stem cells protection