Fermented Coix seed hydrolysate upregulates skin barrier genes and promotes wound healing

Coix seed (CS), also known as yì yǐ rén or Chinese pearl barley, has been prescribed in traditional Chinese medicine (TCM) for centuries to clear heat, drain dampness, and alleviate inflammatory conditions. It is a key component of classical preparations such as Qing Xin Pei Tu granules and Qin-Zhu-Liang-Xue decoction, traditionally used for atopic eczema and other skin barrier-related disorders. CS has also been applied in topical formulations for acne and chronic ulcers. In modern practice, hydrolyzed and fermented CS products are increasingly utilized for their potential to enhance skin health. However, the mechanisms by which they influence skin barrier function and dermal wound healing remain poorly understood. This study aimed to investigate the effects of hydrolyzed CS and its fermented derivatives on skin barrier gene expression and dermal wound healing, thereby providing scientific support for their cosmetic application. CS was hydrolyzed using mild acid, supplemented with yeast extract, and fermented with Lactiplantibacillus plantarum TKK. The non-fermented CS hydrolysate (NF-AC10Y), fermented cell-free supernatant (FF-AC10Y), and fermented cell lysate supernatant (FL-AC10Y) were evaluated in vitro for their effects on skin barrier genes ( FLG /pro-filaggrin, IVL /involucrin, and LOR /loricrin), dermal wound healing, and oxidative stress protection. Potential metabolites contributing to the bioactivities were also identified. FF-AC10Y exhibited the strongest activity. It upregulated FLG, IVL, and LOR mRNA levels in HaCaT keratinocytes by 2.29 ± 0.19-, 1.20 ± 0.08-, and 2.50 ± 0.04-fold, respectively, and achieved 88.1 ± 6.8 % wound closure in NIH/3T3 fibroblasts. It exhibited no cytotoxicity up to 5 mg/mL and protected both cell types against H₂O₂-induced oxidative stress. Metabolite analysis revealed lactic acid, saccharides, amino acids, fatty acid amides, and low-molecular-weight antioxidants as potential contributors to its bioactivities. FF-AC10Y demonstrates strong potential to reinforce the skin barrier by upregulating FLG, IVL, and LOR expression, supporting wound healing, and providing antioxidant protection. These findings scientifically validate the traditional use of CS in TCM for alleviating skin barrier disorders and clarify its mechanisms, bridging historical applications with modern cosmetic formulations.