Zerumbone from Zingiber zerumbet (L.) Roscoe ex Sm. ameliorates atopic dermatitis by regulating the MAP kinase/NF-κB, Akt, and STAT pathways.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiber zerumbet (L.) Roscoe ex Sm., native to tropical and subtropical Asia, has long been used to treat gastrointestinal disorders, allergies, asthma, and skin diseases. Zerumbone, its principal bioactive compound, has attracted interest for its anti-inflammatory, anticancer, antioxidant, antidiabetic, and antihyperlipidemic properties. AIM OF THE STUDY: Conventional therapies for atopic dermatitis (AD) often provide only transient relief and may cause adverse effects. Although modern immunomodulators show strong efficacy, their high-cost limits accessibility. Thus, identifying natural compounds with potent efficacy and minimal side effects is crucial. This study examined the therapeutic potential and mechanisms of zerumbone in AD-like inflammation. MATERIALS AND METHODS: An in vitro model using TNF-α/IFN-γ (TI)-stimulated HaCaT keratinocytes was employed to evaluate inflammatory signaling and cytokine expression. In vivo, AD-like symptoms were induced in BALB/c mice using 2,4-dinitrochlorobenzene (DNCB). Pro-inflammatory cytokines and chemokines were quantified by RT-qPCR, while histopathological and physiological assessments were performed to evaluate skin integrity and inflammation. RESULTS: Zerumbone inhibited MAPK/NF-κB, STAT, and Akt phosphorylation in TI-stimulated HaCaT cells and suppressed pro-inflammatory cytokine and chemokine mRNA levels. It also restored filaggrin, loricrin, and involucrin expression, essential for skin barrier function. In DNCB-induced AD mice, zerumbone reduced erythema, transepidermal water loss, ear thickness, and scratching while improving hydration. It also downregulated inflammatory cytokines and enhanced barrier protein expression. CONCLUSIONS: Zerumbone exerts potent anti-inflammatory and barrier-restorative activities in both cellular and animal models of atopic dermatitis, supporting its potential as a promising natural therapeutic candidate for AD and related inflammatory skin disorders.