A Cornflower Extract Containing N-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 via 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 in silico molecular modeling and a generic screening assay were developed to screen natural molecules binding and blocking these two chemokines. N-Feruloylserotonin was identified as a neutraligand of CCL22 in these experiments. A cornflower extract containing N-feruloylserotonin was selected for further in vitro 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 N-feruloylserotonin for cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymatic cellular inhibition. The cornflower extract was shown to neutralize the two chemokines in vitro, inhibited COX-2 and 5-LOX, and demonstrated anti-inflammatory activities due mainly to the presence of N-feruloylserotonin. Although these findings would need to be confirmed in an in vivo study, the in vitro studies lay the foundation to explain the benefits of the cornflower extract when applied topically to individuals with atopic-prone skin.

N-Feruloyl Serotonin Attenuates Neuronal Oxidative Stress and Apoptosis in Aβ25–35-Treated Human Neuroblastoma SH-SY5Y Cells

“…First, to development of prevention and treatment materials in AD, further studies are needed to focus on the neuroprotective effects of FS under in vivo system such as animal and clinical studies. Previous studies have demonstrated beneficial effects of FS such as anti-inflammatory effect and anti-atopic dermatitis under in vivo system [ 17 , 67 ]. However, in the current stage, lack of enough data to support the neuroprotective effect of FS under in vivo system.…”

“…N -feruloyl serotonin (FS; Figure 1 ) belongs to polyphenols [ 14 ], is a member of serotonin derivatives found in the seeds from safflower and Leuzea carthamoides , and cornflower [ 15 , 16 , 17 ]. Previous findings have revealed that FS exerts health beneficial effects such as anti-inflammation, antioxidant, and anti-apoptotic properties [ 18 , 19 , 20 ].…”

Herbicide resistance status impacts the profile of non-anthocyanin polyphenolics and some phytomedical properties of edible cornflower (Centaurea cyanus L.) flowers

“…The anti-inflammatory properties of cornflower flowers were confirmed by pharmacological experiments 10 . Cornflower extracts inhibited cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) and had anti-inflammatory activities mainly due to the presence of N-feruloylserotonin (able to inhibit 5-LOX and COX) 41 , whereas apigenin was the most effective XO inhibitor identified in C. virgata Lam 42 .…”

Anti-skin aging activity of eggshell membrane administration and its underlying mechanism

“…In addition, oral administration of ESM reversed the UVB-induced elevation in cytokine expression (Fig. 5A), and reduced the mRNA expression of cyclooxygenase-2 (COX-2), which is the enzyme responsible for causing inflammation (Carola et al 2021). Next, we investigated the expression levels of antioxidant enzymes to confirm their relation to the suppression of cytokine expression in the ESM-treated group.…”