Total Panax notoginseng Saponins Repair the Epidermal Barrier by Regulating a Multi-Pathway Network: Insights from an Integrative RHE Model and Multi-Omics Study

三七总皂苷通过调节多通路网络修复表皮屏障:来自整合性RHE模型和多组学研究的启示

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Abstract

The abnormal barrier function of the stratum corneum is a significant characteristic of surface-active agent-induced inflammatory skin diseases, and its cause is closely related to the abnormal lipid components of the stratum corneum. Total saponins of Panax notoginseng (TSPN) have significant potential in improving inflammatory skin barrier function. This study aims to investigate the barrier repair efficacy of TSPN using the EpiKutis(®) skin model and to explore the potential mechanisms through multi-omics analysis based on transcriptomics, proteomics, and lipid metabolomics. We found that TSPN could ameliorate Sodium dodecyl sulfate (SDS)-induced barrier impairment in the EpiKutis(®) model, alleviating stratum corneum thickening and upregulating the expression of barrier-related proteins, e.g., Filaggrin, Involucrin, and Loricrin. Through an integrated multi-omics network, we identified seven key target proteins and screened six lipid metabolites, which are involved in lipid metabolism and exert barrier-repairing effects through five pathways. The result indicated that TSPN might repair the epidermal barrier by regulating the phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT)-mediated proliferation pathway, Mitogen-activated protein kinase (MAPK)-mediated apoptotic pathways, sphingolipid synthesis, Calcium/calmodulin-dependent protein kinase II beta (CAMK2B)-mediated actin cytoskeleton regulation, and Inositol-trisphosphate 3-kinase B (ITPKB)-mediated phosphatidylinositol signaling system. Further study is needed to explore the mechanism of the molecular link between lipid abnormalities and skin barrier function.

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