Integrative effects of an oral supplement mixture containing melon, yeast extract, and licorice on skin pigmentation reduction: Insights from a zebrafish model and a randomized double-blind controlled pilot human trial

Introduction: Intrinsic aging (e.g., genetic and metabolic changes) and extrinsic factors (e.g., sun exposure and environmental pollution) contribute to skin pigmentation and aged facial appearance. Plant extracts, known for their antioxidant properties, may influence skin pigmentation both directly and indirectly through pigment metabolism in the liver, potentially mitigating the effects of aging. Objective: This study investigates the effects of a mixture of melon, yeast extract, and licorice (Mix) oral supplement on liver metabolism and skin pigmentation. Methods: A zebrafish model of chemical liver injury was established using acetaminophen (APAP). Liver and yolk sac areas were analyzed, and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) activity and total bilirubin content were measured to assess the supplement’s protective effects. Additionally, a zebrafish pigmentation model was induced with menadione, and yolk sac pigmentation intensity was analyzed. A pilot randomized, double-blind, placebo-controlled clinical trial was conducted with 22 healthy female volunteers randomly assigned to either the experimental or placebo group. Participants consumed 700 mg of the mixture (Mix) daily for 8 weeks. Skin brightness (L*), yellowness (b*), individual typology angle (ITA°), and melanin index (MI) were measured using a skin colorimeter (CL 400), melanin meter (MX 18), and VISIA 7 at baseline, 4 weeks, and 8 weeks. Results: In the zebrafish liver injury model, the mixture group（Mix Group）showed a significant increase in liver surface area, a decrease in yolk sac area, increased UGT1A1 activity, and reduced total bilirubin levels compared to the model control group. In the zebrafish pigmentation model, yolk sac pigmentation intensity was lower in the mixture group（Mix Group）. The pilot human trial demonstrated that participants taking the mixture (Mix) experienced significant improvements in skin brightness (L*) and ITA°, along with reductions in skin yellowness (b*) and melanin index (MI) after 4 and 8 weeks. Conclusion: An oral supplement comprising bioactive compounds from melon, yeast extract, and licorice effectively reduce skin pigmentation and supports liver pigment metabolism. This formulation, with its demonstrated functional food properties, suggests potential as an anti-aging intervention. Keywords: Skin pigmentation; Liver; Oral supplements; Plant extracts; Antioxidants; Zebrafish