Therapeutic potential of phytochemical luteolin in restoring skin barrier by inhibiting antimicrobial peptides associated with TRAF6/TAK1/IKK/IκB in psoriasis-like HaCaT models.

UNLABELLED: Autoimmune skin diseases, such as psoriasis are primarily characterized by excessive inflammation and skin barrier damage. The disrupted skin barrier is directly related to skin dryness. Luteolin, a flavonoid compound, has various biological activities such as antioxidant, anticancer, anti-aging, and anti-inflammatory. However, little has been known about the anti-psoriatic therapeutic function of luteolin. This study focused on the recovery of the skin barrier by luteolin through the regulation of antimicrobial peptides (AMPs) as well as anti-inflammatory activity, using TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. First, luteolin significantly inhibited the mRNA expression of antimicrobial peptides LL-37, human β-defensin-2 (hBD-2), S100A7, and S100A8 by regulating IκB/NF-κB signaling pathway through TRAF6/IκB. Moreover, luteolin increased the expression of filaggrin, loricrin and involucrin, which are essential of cornified envelope (CE) formation in epidermis. These results suggest anti-inflammatory luteolin has the function of restoring the disrupted skin barrier by regulating antimicrobial peptides and cornified envelope proteins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-01894-z.