Integrated chemical profiling, transcriptomics and functional validation elucidate the multifunctional benefits of a...

Skin aging is driven by interconnected hallmarks including oxidative stress and chronic low-grade inflammation, cellular senescence, impaired epidermal function and extracellular matrix (ECM) degradation. Fermentation-derived cosmetic ingredients have attracted increasing interest as multifunctional actives; however, their underlying mechanisms often remain poorly understood. This study aimed to systematically characterize the biological activities and mechanisms of a triple-ferment filtrate complex (TF Complex) derived from fermented rice, green tea and algae.

An integrated approach combining chemical profiling, transcriptomic analysis and functional validation across multiple in vitro skin models was employed. Chemical constituents were characterized using UPLC-Q-Orbitrap-MS. Transcriptomic responses of human keratinocytes treated with TF Complex at different time points were evaluated by RNA sequencing. Functional activities were assessed in keratinocytes, fibroblasts and reconstructed human skin models relevant to skin aging.

Chemical profiling revealed a compositionally complex mixture containing diverse bioactive constituents. Transcriptomic analysis revealed a time-dependent response characterized by early activation of antioxidant defence pathways, followed by induction of epidermal differentiation related programmes. Functional studies showed that TF Complex promoted wound closure and attenuated UVB-induced inflammatory responses. Furthermore, selected representative constituents, turanose, caffeine and p-hydroxybenzaldehyde, enhanced antioxidant and keratinocyte differentiation-associated gene expression while down-regulating inflammation-related gene expression in skin cells. In H₂O₂-induced senescent fibroblasts, TF Complex reduced senescence-associated β-gal activity and p16/γH2AX levels while increasing SOD2 expression. In a reconstructed full-thickness inflammaging skin model, TF Complex restored epidermal thickness and filaggrin expression, preserved dermal-epidermal junction integrity and dermal ECM proteins and reduced the release of MMP-1, MMP-9 and IL-1α.

TF Complex exerts multifunctional activities relevant to skin aging intervention through coordinated regulation of oxidative stress responses, inflammation and epidermal homeostasis. These findings provide a comprehensive mechanistic framework supporting the development and application of fermentation-derived cosmetic actives for healthy skin aging.