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Ginsenoside Compound K activates EGFR to enhance the skin barrier- and moisturization-related molecules

Year: 2026

Type: article

Abstract: Background: Ginseng is a well-known tonic herb used for thousands of years. Ginsenosides, the major components of ginseng, exhibit various biological functions. Among these, their roles in skin health attract increasing attention. Compound K (C-K), a secondary metabolite of ginsenosides, has been reported to enhance skin moisturization and melanin secretion. However, the upstream signaling pathways have not been clearly clarified. Methods: Cell viability assay assessed the cytotoxicity of C-K, and luciferase reporter gene assay screened potential signaling pathways. Quantitative polymerase chain reaction (qPCR) evaluated the mRNA levels of skin barrier- and hydration-related genes. Western blot and Cellular Thermal Shift Assay (CETSA) confirmed the signalings and targets, while molecular docking predicted residues. Results: Cell viability assays showed C-K exhibited no significant cytotoxicity in HEK293T at 10 μM and in HaCaT cells at 3 μM. C-K also promoted the mRNA expressions of FLG, HAS-2, AQP3, loricrin, and involucrin. Luciferase assay and qPCR treated with inhibitors revealed that C-K activated mitogen-activated protein kinases (MAPKs), nuclear factor kappa-B (NF-κB), and cyclic AMP response element-binding protein (CREB) signaling pathways, which were confirmed by western blotting. CETSA further identified epidermal growth factor receptor (EGFR) as a potential target of C-K, and molecular docking showed putative interactions between C-K and the residues of EGFR. Conclusion: Taken together, C-K exhibited potent effects in enhancing skin barrier and hydration by phosphorylated EGFR at Tyr1173, thereby activating MAPKs, NF-κB, and CREB signaling cascades. These findings provide fundamental evidence supporting the use of C-K as a cosmetic ingredient and a promising option for skin protection.

Source: Journal of Ginseng Research

DOI: 10.1016/j.jgr.2026.101117