Effects of a Novel Oral Melon-Derived Supplement on Skin Pigmentation Reduction: Insights from a Zebrafish Model and a Randomized Double-Blind Controlled Human Trial Jiani Zheng

Introduction: In a prior study, we found that rice-derived glucosylceramides (GlCer) improved overall health and alleviated common cold symptoms, including nasal congestion, sore throat, coughing, headache, muscle pain, and diarrhea. One of the underlying mechanisms may involve the enhanced activation of antigen-presenting cells (APC) through Mincle, a c-type lectin receptor, and toll-like receptors. However, the clinical impact of GlCer on cell-mediated innate immunity, especially concerning APC, is not yet fully understood. Objective: Therefore, we performed a clinical study on the effects of commercially available rice-GlCer (Oryza Ceramide®) on blood dendritic cells (DC). Methods: The study was planned as a randomized, placebo-controlled, double-blind trial. Oryza Ceramide®-PCD (OC-PCD, 20 mg) tablets, each containing 0.6 mg of GlCer, were used as the active tablet. Twenty-two healthy Japanese individuals were enrolled and randomly divided to an active group (n=11) or placebo group (n=11 For 8 weeks, participants took three active tablets (60 mg of OC-PCD) or three placebo tablets daily. DC ratios and CD expression on DC during the intervention were set as the primary outcomes. Results: All subjects finished the trial, and the per protocol set constituted 11 in each group. The myeloid DC (mDC) ratio and CD86 expression were significantly lower in the active group than in the placebo group. In contrast, HLA-DR expression on mDC was slightly higher in the active group. A stratified analysis of subjects with mean fluorescence intensity (MFI) for HLA-DR <60,000 revealed a significant high value in HLA-DR expression in the active group. A correlation was observed between changes in MFI values for HLA-DR and CD86 on mDC. However, plasmacytoid DC parameters did not change. Novelty of the Study: Rice-derived GlCer was firstly clarified to enhance innate immune response specifically mDC to improve common cold symptoms through this clinical trial. Conclusions: The oral administration of GlCer affected mDC by up-regulating the expression of HLA-DR and down-regulating CD86, which contribute to antigen presentation to T lymphocytes. The present results suggests that GlCer attenuate cold symptoms by enhancing the interaction between mDC and T lymphocytes. Trial Registration: UMIN-CTR: UMIN000055299 Keywords: rice; glucosylceramide; HLA-DR; dendritic cells; CD86