Mechanism of therapeutic effects of oral administration of bioprocessed black rice bran and balloon flower root (Platycodon grandiflorum) individually and in combination against atopic dermatitis in mice

Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder frequently associated with dysregulated Th1/Th2 immune balance and impaired regulatory T (Treg) activity. Although conventional treatments can reduce clinical symptoms, concerns regarding long-term adverse effects have led to increased interest in complementary and functional dietary materials with immunomodulatory potential. Bioprocessed black rice bran (BRB-F) and balloon flower root fractions (BFR-F) have individually demonstrated anti-inflammatory activities, but their combined oral efficacy and mechanisms in AD remain insufficiently characterized. Methods Mechanistic in vitro assays were first performed using a human B-cell line to measure IgE secretion, mouse and/or human mast cells to evaluate degranulation and TSLP release, and keratinocyte cultures to quantify TARC, MDC, and IL-6 production. These assays were used to determine whether BRB-F and BFR-F individually or cooperatively modulate immune and epithelial cell activation relevant to AD pathology. Subsequently, an AD-like phenotype was induced in BALB/c mice by topical application of 1-chloro-2,4-dinitrobenzene followed by mite extract. Animals received dietary supplementation with a 3:1 BRB-F:BFR-F mixture (10–80 mg/kg/day), and clinical skin inflammation, ear histopathology, and cytokine profiles were analyzed to assess Th1/Th2 balance and Treg-associated markers. Results Dietary supplementation with the BRB-F:BFR-F binary combination resulted in dose-dependent improvement in AD-like skin lesions and reduced histopathological severity. The mixture suppressed Th2 cytokines (IL-4, IL-5, IL-13) in ear tissue and increased splenic Th1 cytokines (IL-2, IL-12, IFN-γ), accompanied by dose-dependent elevation of galectin-9, suggesting activation of Treg-associated pathways. IL-10 expression was also reduced in vivo. In vitro, BRB-F and BFR-F cooperatively inhibited IgE production by B cells, attenuated mast cell activation and TSLP release, and lowered keratinocyte secretion of TARC, MDC, and IL-6. Conclusions The combined oral administration of bioprocessed BRB-F and BFR-F exerts multi-targeted anti-atopic activity that includes modulation of Th1/Th2 immune balance, activation of Treg-associated signaling, and suppression of B-cell, mast cell, and keratinocyte responses. These findings, confirmed by histopathology of skin tissues before and after treatment, provide preclinical support for the development of BRB-F:BFR-F as a complementary functional material for managing immune dysregulation associated with AD, although validation in human patients will be required.