Efficacy of SGPP2 Modulation-Mediated Materials in Ameliorating Facial Wrinkles and Pore Sagging

Abstract

Skin aging is a complex process with internal and external factors. Recent studies have suggested that enlargement and elongation of skin pores may be early signs of aging in addition to wrinkles and loss of elasticity. This study explores the potential of targeting the SGPP2 gene in keratinocytes to address these emerging concerns. Using siRNA knockdown, we demonstrated that SGPP2 modulates the production of inflammatory cytokines (interleukin (IL)-1β and IL-8). Furthermore, conditioned media experiments revealed that keratinocytes with high SGPP2 expression indirectly influence fibroblast extracellular matrix remodeling, potentially contributing to enlarged pores and wrinkle formation. Based on these findings, we explored a complex formulation containing four SGPP2-modulating compounds. In vitro and in vivo experiments demonstrated the efficacy of the formulation in mitigating fine wrinkles and pore enlargement. This study highlights the significant implications of developing a more effective antiaging cosmetic formulation by targeting underlying inflammatory processes that drive skin aging.

Keywords: cosmetics; inflammation; pore sagging; skin aging; skin wrinkle; wrinkle improvement.

Figure 1

SGPP2 expression and SGPP2 knockdown effects in HaCaTs under inflammatory conditions. (a) Changes in sphingosine-1-phosphate phosphatase 2 (SGPP2) gene expression over time in lipopolysaccharide (LPS)-treated (1 ug/mL) and tumor necrosis factor (TNF)-α treated (10 ng/mL) HaCaT cells (b) Expression of other inflammatory cytokines in LPS-treated and TNF-α treated HaCaT cells (c) Downregulation of SGPP2 expression using three siRNAs (siSGPP2) compared to negative control siRNA (siNC) (d) Expression of genes associated with skin inflammation and barrier stress-related genes in SGPP2-knockdown cells. Bars indicate standard deviation (n = 3). *** p < 0.001, ** p < 0.01, * p < 0.05; Student’s t-test.

Figure 2

Expression of genes associated with human skin ECM under inflammatory conditions compared to senescence-like normal human dermal fibroblasts (NHDFs). Relative expression of Col1a1, Col4a1, ELN, and MAGP-1 in young NHDFs with or without IL-8 (10 ng/mL) for 24 h and in senescence-like NHDFs, which were cultured for more than 20 passages. Bars indicate standard deviation (n = 3). Data were compared between young NHDFs treated with or without IL-8. *** p < 0.001, ** p < 0.01, * p < 0.05; Student’s t-test.

Figure 3

Screening materials with the ability to downregulate SGPP2 expression and IL-8 inflammatory cytokine. (a) Relative expression of SGPP2 in keratinocytes (HaCaT) treated with Fucoidan, Feruloyl Serotonin (FS), Hyaluronic acid (HA), and Polygonum cuspidatum root extract (PCE) at the mentioned concentrations. All samples except Negative control (NC) are treated with LPS (1 ug/mL). (b) Anti-inflammatory effect of SGPP2-downregulating materials that decreases IL-8 expression in LPS-treated keratinocytes. Bars indicate standard deviation (n = 3). *** p < 0.001, ** p < 0.01, * p < 0.05; Student’s t-test.

Figure 4

Analysis of ECM-enhancing effects in dermal fibroblast of SGPP2 expression-regulating materials through in vitro experiments. (a) Relative expression of MAGP-1, Col1a1, and ELN genes in normal human dermal fibroblast treated with conditioned medium (CM) for 24 h produced by LPS-treated HaCaT cells cultured in Fucoidan, Feruloyl Serotonin (FS), Hyaluronic acid (HA) and Polygonum cuspidatum Root extract (PCE) for 24 h at the mentioned concentrations. (b) Analysis of changes in type I collagen synthesis in human dermal fibroblasts treated with CM. Bars indicate standard deviation (n = 3). Data were compared between LPS-treated groups treated with and without each substance. *** p < 0.001, ** p < 0.01, * p < 0.05; Student’s t-test.

Figure 5

Dermal collagen upregulation in 3D skin model by treatment with formulations containing SGPP2 modulating materials. (a) Effect of two cram formulations on increasing dermal collagen area in 3D skin equivalent; (b) Representative images cross sections of 3D skin equivalent; scale bar = 275 um. Black arrows indicate the dermis as visualized with Masson Trichrome stain. Bars indicate standard deviation (n = 3). ** p < 0.01; Student’s t-test.

Figure 6

Facial wrinkle and pore improvement by the LG formula containing SGPP2 expression-regulating materials. (a) Comparison of the undereye fine wrinkle improvement rate; (b) Comparison of the mean pore area improvement rate between LG formula- and 0.1% retinol-treated groups after four weeks. Representative images were acquired using an Antera 3D camera both pre- and post-treatment (4 weeks). Bars indicate standard deviation (n = 19). ** p < 0.01, * p < 0.05; Student’s t-test.