Red Ginseng Crude Saponin Attenuates Di-(2-ethylhexyl) Phthalate-Exacerbated Atopic Dermatitis by Suppressing Allergic Inflammation

Background/Objectives: Low-dose phthalate exposure acts as an adjuvant for immunoglobulin production and exacerbates atopic dermatitis (AD)-like lesions; however, research on orally administered di-(2-ethylhexyl) phthalate (DEHP)-mediated AD aggravation remains limited. This study evaluated the protective effects of crude saponins from red ginseng (CS) against DEHP-aggravated AD using a 2,4-dinitrochlorobenzene (DNCB)-induced male BALB/c mouse model. Methods: AD was induced by repeated topical DNCB application, followed by oral DEHP exposure with concurrent CS application at three doses (5, 15, and 50 mg/kg). Clinical severity scores, skin histopathology, organ indices, and serum allergic mediators were assessed. Results: DEHP exposure significantly increased erythema, edema, excoriation, epidermal/dermal thickening, and tissue eosinophil and mast cell infiltration. CS treatment markedly reduced clinical scores, eosinophil infiltration, and plasma histamine, serum immunoglobulin E (IgE), interleukin-5 (IL-5), and thymic stromal lymphopoietin (TSLP), suppressing Th2-biased systemic inflammation. Conclusions: These findings indicate that CS attenuates DEHP-exacerbated AD-like inflammation in a mouse model, potentially through modulation of Th2-associated allergic responses. Although further validation in human-relevant models is required, these results provide proof-of-concept evidence supporting the investigation of standardized red ginseng saponin preparations as potential adjunctive approaches for environmentally aggravated AD.