Glycation is a process in which reducing sugars bind to proteins, resulting in the formation of advanced glycation end products (AGEs). These AGEs accumulate in the skin, promote excessive collagen crosslinking, and disrupt the extracellular matrix (ECM), impairing normal cellular functions and contributing to skin aging. To evaluate the anti-glycation efficacy of lotus stamen extract (LSE), we employed the BSA–fructose system and a high glucose (HG)-induced fibroblast glycation model. The results demonstrated that LSE effectively inhibited cellular glycation and also exhibited anti-inflammatory, antioxidative, and anti-senescent effects in HG-induced human skin fibroblasts (HSF). Further investigation into the anti-glycation mechanism and component analysis of the lotus stamen ethyl acetate extract (LSEE) led to the identification of 15 flavonoids. The anti-glycation results indicated that these flavonoids are likely the primary active constituents in LSE. Mechanistic studies revealed that GLO1 plays a crucial role in cellular resistance to glycation, and LSEE enhanced GLO1 expression through the Nrf2/Keap1 pro-survival pathway, thereby mitigating intracellular AGE production. In summary, LSEE and its multiple flavonoid components exhibit potent intracellular anti-glycation activity and present significant potential to be developed as a natural and organic product for cosmetic and healthcare applications.

Gardeniae Fructus (GF), a traditional Chinese medicine rich in iridoids, has demonstrated skin-improving effects. However, its mechanisms for enhancing epidermal barrier function remain unclear. In this study, the iridoids in GF were characterized using UPLC-MS/MS. The improvement in the barrier function by GF was assessed through in vitro experiments and a human efficacy assessment. In addition, the potential targets were predicted through proteomics analysis, molecular docking, and molecular dynamics (MD), and verified in HaCaT cells and three-dimensional epidermal models. Nine iridoids were identified in GF. In vitro, GF effectively promoted cell migration and reduced cell damage and oxidative stress. Proteomics analysis combined with molecular docking and MD simulations predicted that the primary iridoids in GF ameliorate barrier function by binding to the aryl hydrocarbon receptor (AHR) with high affinity and stability. Subsequent validation demonstrated that GF significantly upregulated AHR, filaggrin (FLG), loricrin (LOR), and involucrin (IVL) mRNA and protein expression. A 28-day randomized double-blind human efficacy assessment in subjects with sensitive skin showed that the gel with GF increased stratum corneum hydration, reduced transepidermal water loss (TEWL), and lowered erythema index and lactic acid tingling. These findings suggest that GF enhances the skin barrier via AHR activation-mediated upregulation of barrier proteins, supporting its cosmeceutical potential.