Ginsenoside Compound K activates EGFR to enhance the skin barrier- and moisturization-related molecules
- 1School of Life Sciences, Huaiyin Normal University, Huai'an, 223300, China.
- 2Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, Republic of Korea.
- 3Department of Biocosmetics, Sungkyunkwan University, Suwon, Republic of Korea.
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.
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BibTeX
@article{you2026ginsenoside,
title = {{Ginsenoside Compound K activates EGFR to enhance the skin barrier- and moisturization-related molecules}},
author = {Long You and Yeye Hu and Zuo Zhang and Suya Li and Huimin Sun and Chengmei Yu and Jae Youl Cho and Xinfeng Wang},
journal = {Journal of Ginseng Research},
year = {2026},
month = jul,
doi = {10.1016/j.jgr.2026.101117},
url = {https://doi.org/10.1016/j.jgr.2026.101117},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ginsenoside Compound K activates EGFR to enhance the skin barrier- and moisturization-related molecules
AU - Long You
AU - Yeye Hu
AU - Zuo Zhang
AU - Suya Li
AU - Huimin Sun
AU - Chengmei Yu
AU - Jae Youl Cho
AU - Xinfeng Wang
PY - 2026
DA - 2026/07/21
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101117
UR - https://doi.org/10.1016/j.jgr.2026.101117
AB - 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.
SN - 1226-8453
SN - 2093-4947
ER -