Propolis as a natural therapeutic agent for atopic dermatitis via MKK4 pathway regulation

Propolis, a natural resinous compound synthesized by bees from various botanical sources, is widely recognized for its diverse bioactive properties and potential as a functional food. Despite its known benefits, the therapeutic effects of propolis on atopic dermatitis (AD) have not been fully elucidated. This study aimed to evaluate the anti-AD efficacy of propolis, identify its active component, and uncover its molecular target. In TNF-α-stimulated HaCaT keratinocytes, propolis significantly suppressed the secretion of pro-inflammatory cytokines IL-6 and IL-8, as well as chemokines such as MCP-1 and MDC. It also restored the expression of skin barrier proteins, including filaggrin and involucrin. Similar modulatory effects were observed in an AD-like human skin model. In vivo, oral administration of propolis in DNCB-induced AD mice alleviated clinical symptoms, enhanced skin barrier function, reduced scratching behavior, and decreased transepidermal water loss (TEWL). Propolis also normalized the expression of AD-related genes in dorsal skin tissues. Through comparative analysis of its major constituents, caffeic acid phenethyl ester (CAPE) was identified as the principal bioactive compound. Further mechanistic studies demonstrated that both CAPE and propolis directly and selectively target MKK4. Collectively, these findings highlight the therapeutic potential of propolis as a functional food-based intervention for atopic dermatitis [ 1 ] [ 2 ]. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany