Helichrysum Essential Oil Ameliorates Atopic Dermatitis by Suppressing the NLRP3 Inflammasome and Restoring Epidermal Barrier Integrity

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and epidermal barrier dysfunction. The essential oil of Helichrysum (HEO) possesses known anti-inflammatory properties, yet its therapeutic efficacy and underlying mechanisms in AD remain to be fully elucidated. This study aimed to investigate the protective effects of HEO on AD-like skin lesions and to explore its regulatory mechanisms involving the NLRP3 inflammasome and skin barrier proteins. Lipopolysaccharide (LPS)-stimulated HaCaT keratinocytes and RAW264.7 macrophages were treated with HEO to assess cell viability, nitric oxide (NO) production, and the expression of inflammatory mediators (COX-2, iNOS, IL-1β, NLRP3). For in vivo studies, an AD mouse model was induced by repeated application of 1-chloro-2,4-dinitrobenzene (DNCB). Mice were treated topically with HEO, and skin severity scores, ear thickness, and histological changes were evaluated. Expression levels of inflammatory markers and barrier proteins were analyzed via Western blotting and qRT-PCR. Serum levels of cytokines and liver function markers were also measured. Our results showed that, using DNCB-induced AD mouse model, topical application of HEO markedly attenuated dermatitis severity, reduced ear thickness, and suppressed epidermal hyperplasia. Furthermore, HEO treatment alleviated systemic inflammation and liver dysfunction, as evidenced by reduced serum levels of TNF-α, IL-6, AST, ALT, and ALP. Mechanistically, HEO significantly inhibited NO production and downregulated the mRNA and protein expression of COX-2, iNOS, and the NLRP3/IL-1β axis in LPS-stimulated cells. Moreover, it effectively inhibited the activation of NLRP3 inflammasome and altered the expression of skin barrier proteins, Filaggrin and Loricrin, in dorsal tissues of DNCB-treated mice. Together, these data demonstrated that HEO ameliorates AD-like symptoms by suppressing the NLRP3 inflammasome-mediated inflammatory response and restoring epidermal barrier integrity. These findings suggest that HEO is a promising therapeutic candidate for the development of drugs for AD.