Reinforcement of barrier function and scalp homeostasis by Senkyunolide A to fight against dandruff.

OBJECTIVE: Senkyunolide-A (SENKY) can be isolated from Apium graveolens seed oil obtained using supercritical CO2 extraction. SENKY and its parent compounds, the N-butyl phthalides, have been demonstrated to protect cells from CO poisoning, to prevent diabetes mellitus and to decrease cancer cell proliferation. This study was undertaken to evaluate in vitro and in vivo the effect of SENKY on epidermal function improvement, Malassezia effect control, scalp soothing and dandruff reduction via skin protection-related pathways.

METHODS: DNA-array and proteomic studies were performed on human keratinocytes, sebocytes and skin explants to demonstrate SENKY activities. Two clinical evaluations were performed under dermatologist control on 106 volunteers, with greasy or dry scalp, experiencing dandruff, itching and redness. Volunteers tested a shampoo followed, or not, by a leave-on, containing SENKY, or their placebos. Dandruff severity and redness were scored on the scalp. Moisturization and sebum release were recorded using relevant measuring apparatus. Itching and scratching evaluations came from volunteers' self-declarations.

RESULTS: DNA-array studies on keratinocytes showed a clear regulation of skin barrier functions and epidermis defence pathways. Upregulation of epidermal differentiation complex genes was observed. These preliminary observations were reinforced by immunocytochemistry and immunohistochemistry studies showing a significant increase of involucrin, filaggrin, loricrin, SPRR, LC3B and ceramide 2 productions. Tight-junctions and corneodesmosomes were significantly reinforced both in keratinocyte cultures (corneodesmosin, claudin, ZO-1) and in skin explants (desmoglein). DNA-array studies also demonstrated upregulation of genes involved in detoxification and anti-inflammation pathways. Proteomic studies revealed that hBD2 production was increased in keratinocytes in contact with SENKY, whereas IL-8, PGE-2 and TLR-9 releases were repressed as well as sebocyte lipid production. Clinical evaluations confirmed that after 3 weeks, SENKY significantly reduced dandruff intensity, redness, itching and scalp histamine content compared to placebo and beginning of treatment.

CONCLUSION: For the first time, SENKY has been shown to promote scalp homoeostasis by reinforcing barrier and defence functions at both gene and protein levels. It reduces irritation and redness in promoting detoxification and anti-inflammation pathways while controlling the niche of Malassezia. Applied on scalp, SENKY significantly reduces the formation of dandruff and soothes the scalp.