Inhibitory Effect of a Novel Non-Steroidal AMPamide on Inflammation and Sebogenesis by Suppressing TLR4 and TLR6-Mediated Signaling Pathway

Seborrheic dermatitis (SD) is a chronic inflammatory skin disorder that primarily affects areas with increased sebaceous gland activity, and is characterized by erythematous scaly lesions. Malassezia utilizes sebum lipids to produce free fatty acids that may disrupt the epidermal barrier and trigger inflammation in eczematous lesions. However, the pathogenesis and mechanisms underlying the exaggerated inflammatory response and sebogenesis regulation in SD remain unknown. Activation of pattern recognition receptors, including Toll-like receptors (TLRs), is crucial for initiating innate immunity. In the present study, we evaluated the efficacy of a novel antimicrobial cosmetic ingredient, AMPamide, and elucidated its molecular mechanisms underlying the suppression of inflammation and sebogenesis in SD. Specifically, we investigated the inhibitory effect of AMPamide on TLR activation and its impact on downstream signaling pathways in LPS-stimulated HaCaT cells. The effects of AMPamide on lipid production and the expression of related regulatory factors in IGF-1-stimulated SZ95 sebaceous gland cells were also examined. These analyses were performed using RT-qPCR, western blotting, immunofluorescence staining, and Nile Red staining. AMPamide exhibited antiinflammatory and skin barrier-strengthening effects by inhibiting TLR4/6 expression and multiple signaling pathways. Additionally, AMPamide attenuated lipid overproduction and the expression of related regulatory factors in IGF-1-stimulated SZ95 sebaceous gland cells. Therefore, the observed effects of AMPamide on LPS-stimulated human keratinocytes were mediated via blockade of the TLRs-MyD88-MAPK and NF-κB signaling pathway. These results revealed that AMPamide may be a potential therapeutic agent for SD that inhibits TLR4/6 activation.