Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3β/β-Catenin Signaling Pathway
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 huma...
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| Published in | Journal of microbiology and biotechnology Vol. 31; no. 7; pp. 933 - 941 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Korea (South)
The Korean Society for Microbiology and Biotechnology
28.07.2021
한국미생물·생명공학회 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1017-7825 1738-8872 |
| DOI | 10.4014/jmb.2101.01032 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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 ALP, BMP2, and VCAN 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 WNT5A, β-catenin, and LEF1. 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. KCI Citation Count: 1 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 ALP, BMP2, and VCAN 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 WNT5A, β-catenin, and LEF1. 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. |
| Author | Yun, Mi-Young Kim, Ji-Eun Lee, Yun Hee Choi, Hui-Ji Kim, Ji Yea Lee, Jee-Hyun Song, Gyu Yong Bae, Seunghee Cho, So-Hyun An, Sungkwan |
| AuthorAffiliation | 3 Department of Beauty Science, Kwangju Women’s University, Gwangju 62396, Republic of Korea 2 College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea 1 Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea |
| AuthorAffiliation_xml | – name: 3 Department of Beauty Science, Kwangju Women’s University, Gwangju 62396, Republic of Korea – name: 1 Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea – name: 2 College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea |
| Author_xml | – sequence: 1 givenname: Yun Hee surname: Lee fullname: Lee, Yun Hee organization: Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea – sequence: 2 givenname: Hui-Ji surname: Choi fullname: Choi, Hui-Ji organization: College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea – sequence: 3 givenname: Ji Yea surname: Kim fullname: Kim, Ji Yea organization: Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea – sequence: 4 givenname: Ji-Eun surname: Kim fullname: Kim, Ji-Eun organization: College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea – sequence: 5 givenname: Jee-Hyun surname: Lee fullname: Lee, Jee-Hyun organization: College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea – sequence: 6 givenname: So-Hyun surname: Cho fullname: Cho, So-Hyun organization: College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea – sequence: 7 givenname: Mi-Young surname: Yun fullname: Yun, Mi-Young organization: Department of Beauty Science, Kwangju Women’s University, Gwangju 62396, Republic of Korea – sequence: 8 givenname: Sungkwan surname: An fullname: An, Sungkwan organization: Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea – sequence: 9 givenname: Gyu Yong surname: Song fullname: Song, Gyu Yong organization: College of Pharmacy, Chungnam National University, Daejon 34134, Republic of Korea – sequence: 10 givenname: Seunghee surname: Bae fullname: Bae, Seunghee organization: Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University, Seoul 05029, Republic of Korea |
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| Cites_doi | 10.1111/j.1600-0625.2011.01281.x 10.1016/j.cell.2007.06.009 10.1111/jpn.13141 10.1056/NEJMra1103442 10.3839/jksabc.2010.012 10.1101/cshperspect.a015180 10.4103/0974-7753.153450 10.1016/j.semcdb.2012.08.011 10.4103/0019-5154.135525 10.1016/S0190-9622(99)70296-3 10.2165/00003495-200161010-00006 10.1016/j.jaad.2017.02.054 10.18632/oncotarget.12617 10.1080/09168451.2017.1385383 10.1124/dmd.31.8.1065 10.1080/19768354.2018.1523806 10.1016/j.jdermsci.2005.03.010 10.1016/j.ejphar.2014.02.024 10.1111/j.1610-0379.2011.07802.x 10.1067/mjd.2000.103909 10.1016/j.jdermsci.2014.12.007 10.1242/jcs.02793 10.1111/j.1745-7254.2005.00034.x 10.1093/abbs/gmr001 10.1186/1749-8546-5-20 10.1242/jcs.018689 10.1016/j.ejphar.2013.12.035 10.1111/j.1365-2133.2004.05785.x 10.3892/ijmm.2017.3107 10.18632/oncotarget.9059 10.4014/jmb.1810.10050 10.1016/j.cub.2008.12.005 10.1101/gad.14.10.1181 10.1136/bmj.331.7522.951 10.1016/j.jep.2006.06.008 10.1111/j.1440-169X.2007.00907.x 10.1016/j.lfs.2019.05.033 10.1002/jcp.26853 10.1186/s13287-020-01650-6 10.1111/j.1600-0625.2009.01007.x 10.1089/jmf.2013.3031 10.1002/ptr.5101 10.4014/jmb.1908.08018 10.1007/s12257-019-0096-4 10.1073/pnas.1309970110 10.1016/j.jgr.2018.06.001 10.1016/j.devcel.2010.01.016 10.1111/ics.12489 |
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| Keywords | β-catenin AKT dermal papilla hair growth property Ginsenoside Rg4 |
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| SubjectTerms | 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 |
| Title | Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3β/β-Catenin Signaling Pathway |
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