[논문]Ginsenosides repair UVB-induced skin barrier damage in BALB/c hairless mice and HaCaT keratinocytes

Li, Zhenzhuo; Jiang, Rui; Wang, Manying; Zhai, Lu; Liu, Jianzeng; Xu, Xiaohao; Sun, Liwei; Zhao, Daqing

doi:10.1016/j.jgr.2021.05.001

Ginsenosides repair UVB-induced skin barrier damage in BALB/c hairless mice and HaCaT keratinocytes 원문보기

Journal of ginseng research = 高麗人參學會誌, v.46 no.1, 2022년, pp.115 - 125

Li, Zhenzhuo (Jilin Ginseng Academy, Changchun University of Chinese Medicine) , Jiang, Rui (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) , Wang, Manying (Jilin Ginseng Academy, Changchun University of Chinese Medicine) , Zhai, Lu (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) , Liu, Jianzeng (Jilin Ginseng Academy, Changchun University of Chinese Medicine) , Xu, Xiaohao (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) , Sun, Liwei (Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine) , Zhao, Daqing (Jilin Ginseng Academy, Changchun University of Chinese Medicine)

Abstract ▼ AI-Helper

Background: Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. Methods: GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. Results: Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. Conclusion: GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

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표/그림 (6)

그림 Fig. 1. Characterization of GS constituents by UPLC with UV detection at 203 nm. (A) UPLC chromatograms of standard ginsenosides. (B) UPLC chromatogram of GS.
그림 Fig. 2. Effect of topical application of GS on UVB-induced skin barrier damage of hairless mice for 2 weeks. (A) Body weight changes. (B) Schematic diagram of the animal experiment. (C) Representative images of dorsal skin surfaces exposed to UVB as described in (A). (D) Representative micrographs of H&E-stained skin tissue sections. Scale bar = 50 mm. Arrows indicate epidermal thickness. (E) Histogram of epidermal thickness of dorsal skin. (F) TEWL and stratum corneum water content of dorsal skin surfaces. Values are expressed as means ± SD (n = 5). *p < 0.05 vs. the control or UVB + Vehicle group.
그림 Fig. 3. Effect of topical application of GS on expression levels of CE, TJs, and AQP3 proteins in dorsal skin of UVB-irradiated mice. (A) Immunohistochemistry was conducted to monitor the FLG, IVL, Cldn-1, and AQP3 expression levels. Scale bar = 20 μm. Arrows indicate location of mouse epidermis. (B) Immunohistochemical staining density analysis of above proteins was shown, respectively. (C) Protein levels of FLG, IVL, Cldn-1, and AQP3 in dorsal skin of UVB-irradiated mice were analyzed byWestern blot. (D) Relative expression levels of these proteins were quantified by densitometry analyses. GAPDH antibody was used as loading control. Values are expressed as means ± SD (n = 5). *p < 0.05 vs. the control or UVB + Vehicle group.
그림 Fig. 4. Effects of GS treatment on UVB-exposed HaCaT cells. (A) The mRNA levels of FLG, IVL, Cldn-1 and AQP3 were assessed and quantified by qRT-PCR after GS treatment for 15 min. GAPDH mRNA expression was detected as the loading control. (B) After treatment of GS for 24 h, protein levels of FLG, IVL, Cldn-1, and AQP3 were analyzed byWestern blot. (C) Relative expression levels of these proteins were quantified by densitometry analyses. GAPDH antibody was used as loading control. (D) Representative images of FLG, Cldn-1, and AQP3 staining were examined using a Cytation 5 cell imaging multifunctional test system. Scale bar = 20 μm. Values are expressed as means ± SD (n = 3). #p < 0.05, ##p < 0.01, ###p < 0.001 vs. the control group; *p < 0.05, **p < 0.01 vs. the UVB-irradiated group.
그림 Fig. 5. Effects of GS treatment on MAPK signaling pathways in UVB-exposed HaCaT cells. (A) HaCaT cells were irradiated with UVB (40 mJ/cm2) and then treated with GS (0, 2.5, 5, and 10 μg/mL) for 2 h. Phosphorylation status of MAPKs were analyzed by Western blot. (B) Relative expression levels of p-JNK/JNK, p-p38/p38, and p-ERK/ERK were quantified by densitometry analyses. GAPDH antibody was used as loading control. Values are expressed as means ± SD (n = 3). #p < 0.05, ##p < 0.01 vs. the control group; *p < 0.05, **p < 0.01 vs. the UVB-irradiated group.
그림 Fig. 6. Effects of GS ginsenoside monomers in the treatment of UVB-exposed HaCaT cells. (A) HaCaT cells were irradiated with UVB (40 mJ/cm²) then treated with GS ginsenoside monomers, GSM, or GS for 24 h. Protein levels of IVL and AQP3 were analyzed byWestern blot. The composition of various monomers in GS is shown as Fig. 1. (B) Relative expression levels of IVL and AQP3 were quantified by densitometry analyses. (C) HaCaT cells were irradiated with UVB (40 mJ/cm²) and then treated with GSM (0, 2.5, 5, and 10 μg/mL) for 2 h. Phosphorylation status of MAPKs were analyzed byWestern blot. (D) Relative expression levels of p-JNK/JNK, p-p38/p38, and p-ERK/ERK were quantified by densitometry analyses. GAPDH antibody was used as loading control. Values are expressed as means ± SD (n = 3). #p < 0.05, ##p < 0.01, ###p < 0.001 vs. the control group; *p < 0.05, **p < 0.01 vs. the UVB-irradiated group.

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