A Cornflower Extract Containing <i>N</i>‐Feruloylserotonin Reduces Inflammation in Human Skin by Neutralizing CCL17 and CCL22 and Inhibiting COX‐2 and 5‐LOX

Abstract

Thymus and Activation-Regulated Chemokine (TARC/CCL17) and Macrophage-Derived Chemokine (MDC/CCL22) are two key chemokines exerting their biological effect <i>via</i> binding and activating a common receptor CCR4, expressed at the surface of type 2 helper T (Th2) cells. By recruiting Th2 cells in the dermis, CCL17 and CCL22 promote the development of inflammation in atopic skin. The aim of this research was to develop a plant extract whose biological properties, when applied topically, could be beneficial for people with atopic-prone skin. The strategy which was followed consisted in identifying ligands able to neutralize the biological activity of CCL17 and CCL22. Thus, an <i>in silico</i> molecular modeling and a generic screening assay were developed to screen natural molecules binding and blocking these two chemokines. <i>N</i>-Feruloylserotonin was identified as a neutraligand of CCL22 in these experiments. A cornflower extract containing <i>N</i>-feruloylserotonin was selected for further <i>in vitro</i> tests: the gene expression modulation of inflammation biomarkers induced by CCL17 or CCL22 in the presence or absence of this extract was assessed in the HaCaT keratinocyte cell line. Additionally, the same cornflower extract in another vehicle was evaluated in parallel with <i>N</i>-feruloylserotonin for cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymatic cellular inhibition. The cornflower extract was shown to neutralize the two chemokines <i>in vitro</i>, inhibited COX-2 and 5-LOX, and demonstrated anti-inflammatory activities due mainly to the presence of <i>N</i>-feruloylserotonin. Although these findings would need to be confirmed in an <i>in vivo</i> study, the <i>in vitro</i> studies lay the foundation to explain the benefits of the cornflower extract when applied topically to individuals with atopic-prone skin.