The present study investigated the protective effects of Sargassum horneri (S. horneri)
ethanol extract (SHE) against
atopic dermatitis (AD), known as an abnormal immune response in house dust mite (HDM)/
2,4-dinitrochlorobenzene (
DNCB)-stimulated NC/Nga mice. The
oral administration of SHE attenuated the AD symptoms, including the skin
dermatitis severity, transepidermal water loss (TEWL), and ear
edema in HDM/
DNCB-stimulated mice. Moreover, the histological analysis revealed that SHE improved epidermal
hyperplasia and hyperkeratosis, and reduced the dermal infiltrations of mast cells and eosinophils. Moreover, SHE downregulated the expression levels of
cytokines (
interleukin (IL)-6, IL-10, and
interferon (IFN)-γ) and
chemokines (Regulated on Activation, Normal T Cell Expressed and Secreted (
RANTES), Eotaxin, and
Thymus and activation-regulated chemokine (TARC)) by decreasing the expression levels of atopic initiators (IL-25 and IL-33) in HDM/
DNCB-stimulated skin. The
oral administration of SHE decreased the spleen size, reducing expression levels of AD-related
cytokines (IL-4, IL-5, IL-6, IL-10,
IL-13, IFN-γ, and TARC) by regulating the expressions of Tbx21 (T-bet), GATA
Binding Protein 3 (GATA-3), and
Signal transducer and activator of transcription 3 (STAT3). Moreover, SHE significantly attenuated the serum
immunoglobulin (Ig)G1 and
IgG2a levels in HDM/
DNCB-stimulated mice. Collectively, these results suggest that S. horneri could be an ingredient of functional food against abnormal immune response.