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Rauvolfia nukuhivensis  is a well-known plant used for its wide range of beneficial effects in Marquesas islands. It is made up of diverse indole alkaloids and is used as traditional medicine for skin application. The actual mechanism behind the virtue of this plant is still unknown. Hence, in this study we aimed at deciphering the impact of  R .  nukuhivensis  on skin immune system in context of (1) homeostasis, (2) pathogen infection and (3) inflammation. Here we show that  R .  nukuhivensis  enhances cellular metabolic activity and wound healing without inducing cellular stress or disturbing cellular homeostasis. It reinforces the epithelial barrier by up-regulating hBD-1. Nevertheless, in pathogenic stress,  R .  nukuhivensis  acts by preparing the immune system to be reactive and effective directly. Indeed, it enhances the innate immune response by increasing pathogens sensors such as TLR5. Finally,  R .  nukuhivensis  blocks IL-22 induced hyperproliferation  via  PTEN and Filaggrin up-regulation as well as BCL-2 downregulation. In conclusion, this study provides evidence on the several cutaneous application potentials of  R .  nukuhivensis  such as boosting the immune response or in restoring the integrity of the epithelial barrier.

R. nukuhivensis acts by reinforcing skin barrier function, boosting skin immunity and by inhibiting IL-22 induced keratinocyte hyperproliferation