Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3β/β-Catenin Signaling Pathway

• Published in: Journal of microbiology and biotechnology Vol. 31; no. 7; pp. 933 - 941
• Main Authors: Lee, Yun Hee, Choi, Hui-Ji, Kim, Ji Yea, Kim, Ji-Eun, Lee, Jee-Hyun, Cho, So-Hyun, Yun, Mi-Young, An, Sungkwan, Song, Gyu Yong, Bae, Seunghee
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society for Microbiology and Biotechnology 28.07.2021; 한국미생물·생명공학회
• Subjects: beta Catenin - metabolism; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell Survival - drug effects; Dermis - cytology; Dermis - drug effects; Dermis - metabolism; Ginsenosides - pharmacology; Glycogen Synthase Kinase 3 beta - metabolism; Hair - drug effects; Hair - growth & development; Hair Follicle - cytology; Hair Follicle - drug effects; Hair Follicle - growth & development; Hair Follicle - metabolism; Humans; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Research article; Signal Transduction - drug effects; Spheroids, Cellular; Wnt Proteins - metabolism; 생물학; β-catenin; AKT; dermal papilla; hair growth property; Ginsenoside Rg4
• ISSN: 1017-7825; 1738-8872
• DOI: 10.4014/jmb.2101.01032

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 μg/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including , , and in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including , , and . In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.