Flavonoids with Two OH Groups in the B-Ring Promote Pigmented Hair Regeneration.

During the process of skin regeneration following a skin injury, de novo hair follicle regeneration is initiated after wounding; however, these regenerated hairs are mostly unpigmented. The activation of epidermal melanocyte stem cells and their differentiation into regenerating hair follicles have been shown to be necessary for the pigmented hair regeneration after wounding. To determine the role of flavonoids in the regeneration of pigmented hairs, we applied the candidate flavonoids to the regenerating hair follicles after wounding and identified the flavonoid species that maximally induced pigmented hair regeneration. Flavonoids with two OH groups in the B-ring, such as sterubin, luteolin, and hydroxygenkwanin, showed promising effects in regenerating black pigmented hairs, while those with one OH group in the B-ring showed no significant change. Thus, flavonoids with two OH groups in their B-ring could be studied further as potential wound healing agents with the ability to regenerate pigmented hair.

Pigmentation of regenerated hairs after wounding.

BACKGROUND: After severe wounding, hair follicles were known to be regenerated de novo along with the re-epithelialization. However, the regenerated hairs lack pigmentation. OBJECTIVE: We aimed to find out the condition to regenerate pigmented hairs after severe wounding. METHODS: De novo hair regeneration was observed during the re-epithelialization process after the full thickness excision of dorsal skin. Hair pigmentation mechanism was assessed by the modulation of Wnt and Kit signalings. RESULTS: Stable regeneration of pigmented hairs was demonstrated when a wound was created to the mice during the anagen stage of the hair cycle. A significant increase in the number of melanocyte stem cells in the postnatal 1st anagen interfollicular skin of 5-week-old mice was observed. An increase of Wnt7a of the keratinocytes was observed in the skin at this stage, which may direct melanocyte stem cells to produce pigmented hairs in the regenerating follicles. This was supported by the finding that transgenic mice expressing the melanocyte stimulatory factor Kitl in their skin promoted the regeneration of pigmented hairs irrespective of the stage of the hair cycle. CONCLUSION: Our results provide a new insight into the intimate regulation process between two follicular stem cell systems, keratinocyte stem cells and melanocyte stem cells, during de novo hair regeneration after wounding.