Panax ginseng extract antagonizes the effect of DKK‑1-induced catagen-like changes of hair follicles

Lee,Yonghee; Kim,Su  Na; Hong,Yong  Deog; Park,Byung  Cheol; Na,Yongjoo

doi:10.3892/ijmm.2017.3107

Panax ginseng extract antagonizes the effect of DKK‑1-induced catagen-like changes of hair follicles

Authors:
- Yonghee Lee
- Su Na Kim
- Yong Deog Hong
- Byung Cheol Park
- Yongjoo Na
View Affiliations

Affiliations: Amorepacific R&D Center, Yongin-si, Gyeonggi-do 446-729, Republic of Korea, Department of Dermatology, Dankook Medical College, Cheonan, Chungcheongnam-do 31116, Republic of Korea
Published online on: August 25, 2017 https://doi.org/10.3892/ijmm.2017.3107
Pages: 1194-1200
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It is well known that Panax ginseng (PG) has various pharmacological effects such as anti-aging and anti-inflammation. In a previous study, the authors identified that PG extract induced hair growth by means of a mechanism similar to that of minoxidil. In the present study, the inhibitory effect of PG extract on Dickkopf-1 (DKK-1)-induced catagen-like changes in hair follicles (HFs) was investigated in addition to the underlying mechanism of action. The effects of PG extract on cell proliferation, anti-apoptotic effect, and hair growth were observed using cultured outer root sheath (ORS) keratinocytes and human HFs with or without DKK-1 treatment. The PG extract significantly stimulated proliferation and inhibited apoptosis, respectively, in ORS keratinocytes. PG extract treatment affected the expression of apoptosis-related genes Bcl-2 and Bax. DKK-1 inhibited hair growth, and PG extract dramatically reversed the effect of DKK-1 on ex vivo human hair organ culture. PG extract antagonizes DKK-1-induced catagen-like changes, in part, through the regulation of apoptosis-related gene expression in HFs. These findings suggested that PG extract may reduce hair loss despite the presence of DKK-1, a strong catagen inducer via apoptosis.

View Figures

View References

1	Inui S, Fukuzato Y, Nakajima T, Yoshikawa K and Itami S: Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: A clue to understand paradoxical effects of androgen on human hair growth. FASEB J. 16:1967–1969. 2002.PubMed/NCBI
2	Li L, Mignone J, Yang M, Matic M, Penman S, Enikolopov G and Hoffman RM: Nestin expression in hair follicle sheath progenitor cells. Proc Natl Acad Sci USA. 100:9958–9961. 2003. View Article : Google Scholar : PubMed/NCBI
3	Reynolds AJ and Jahoda CA: Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis. Development. 115:587–593. 1992.PubMed/NCBI
4	Millar SE: Molecular mechanisms regulating hair follicle development. J Invest Dermatol. 118:216–225. 2002. View Article : Google Scholar : PubMed/NCBI
5	Botchkarev VA and Paus R: Molecular biology of hair morphogenesis: Development and cycling. J Exp Zoolog B Mol Dev Evol. 298:164–180. 2003. View Article : Google Scholar
6	Botchkareva NV, Ahluwalia G and Shander D: Apoptosis in the hair follicle. J Invest Dermatol. 126:258–264. 2006. View Article : Google Scholar : PubMed/NCBI
7	Sawaya ME, Blume-Peytavi U, Mullins DL, Nusbaum BP, Whiting D, Nicholson DW, Lotocki G and Keane RW: Effects of finasteride on apoptosis and regulation of the human hair cycle. J Cutan Med Surg. 6:1–9. 2002. View Article : Google Scholar : PubMed/NCBI
8	El-Domyati M, Attia S, Saleh F, Bassyouni M, Barakat M and Abdel-Wahab H: Evaluation of apoptosis regulatory markers in androgenetic alopecia. J Cosmet Dermatol. 9:267–275. 2010. View Article : Google Scholar : PubMed/NCBI
9	Oltvai ZN, Milliman CL and Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 74:609–619. 1993. View Article : Google Scholar : PubMed/NCBI
10	Müller-Röver S, Rossiter H, Lindner G, Peters EM, Kupper TS and Paus R: Hair follicle apoptosis and Bcl-2. J Investig Dermatol Symp Proc. 4:272–277. 1999. View Article : Google Scholar
11	Kwack MH, Ahn JS, Kim MK, Kim JC and Sung YK: Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells. BMB Rep. 43:688–692. 2010. View Article : Google Scholar : PubMed/NCBI
12	Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK and Kim JC: Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J Invest Dermatol. 128:262–269. 2008. View Article : Google Scholar
13	Kwack MH, Kim MK, Kim JC and Sung YK: Dickkopf 1 promotes regression of hair follicles. J Invest Dermatol. 132:1554–1560. 2012. View Article : Google Scholar : PubMed/NCBI
14	Hu S, Concha C, Lin F and Persson Waller K: Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle. Vet Immunol Immunopathol. 91:29–37. 2003. View Article : Google Scholar : PubMed/NCBI
15	Na HS, Lim YJ, Yun YS, Kweon MN and Lee HC: Ginsan enhances humoral antibody response to orally delivered antigen. Immune Netw. 10:5–14. 2010. View Article : Google Scholar : PubMed/NCBI
16	Hong CE and Lyu SY: Anti-inflammatory and anti-oxidative effects of korean red ginseng extract in human keratinocytes. Immune Netw. 11:42–49. 2011. View Article : Google Scholar : PubMed/NCBI
17	Yun TK and Choi SY: Preventive effect of ginseng intake against various human cancers: A case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev. 4:401–408. 1995.PubMed/NCBI
18	Cho S, Won CH, Lee DH, Lee MJ, Lee S, So SH, Lee SK, Koo BS, Kim NM and Chung JH: Red ginseng root extract mixed with Torilus fructus and Corni fructus improves facial wrinkles and increases type I procollagen synthesis in human skin: A randomized, double-blind, placebo-controlled study. J Med Food. 12:1252–1259. 2009. View Article : Google Scholar
19	Kang TH, Park HM, Kim YB, Kim H, Kim N, Do JH, Kang C, Cho Y and Kim SY: Effects of red ginseng extract on UVB irradiation-induced skin aging in hairless mice. J Ethnopharmacol. 123:446–451. 2009. View Article : Google Scholar : PubMed/NCBI
20	Kim S, Kang BY, Cho SY, Sung DS, Chang HK, Yeom MH, Kim DH, Sim YC and Lee YS: Compound K induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and increases hyaluronan in hairless mouse skin. Biochem Biophys Res Commun. 316:348–355. 2004. View Article : Google Scholar : PubMed/NCBI
21	Kwok HH, Yue PY, Mak NK and Wong RN: Ginsenoside Rb(1) induces type I collagen expression through peroxisome proliferator-activated receptor-delta. Biochem Pharmacol. 84:532–539. 2012. View Article : Google Scholar : PubMed/NCBI
22	Lee J, Jung E, Lee J, Huh S, Kim J, Park M, So J, Ham Y, Jung K, Hyun CG, et al: Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling. J Ethnopharmacol. 109:29–34. 2007. View Article : Google Scholar
23	Matsuda H, Yamazaki M, Asanuma Y and Kubo M: Promotion of hair growth by ginseng radix on cultured mouse vibrissal hair follicles. Phytother Res. 17:797–800. 2003. View Article : Google Scholar : PubMed/NCBI
24	Kim SH, Jeong KS, Ryu SY and Kim TH: Panax ginseng prevents apoptosis in hair follicles and accelerates recovery of hair medullary cells in irradiated mice. In Vivo. 12:219–222. 1998.PubMed/NCBI
25	Attele AS, Wu JA and Yuan CS: Ginseng pharmacology: Multiple constituents and multiple actions. Biochem Pharmacol. 58:1685–1693. 1999. View Article : Google Scholar : PubMed/NCBI
26	Leung KW and Wong AS: Pharmacology of ginsenosides: A literature review. Chin Med. 5:202010. View Article : Google Scholar : PubMed/NCBI
27	Kim SN, Kim S, Hong YD, Park H, Shin SH, Kim AR, Park BC, Shin SS, Park JS, Park M, et al: The ginsenosides of Panax ginseng promote hair growth via similar mechanism of minoxidil. J Dermatol Sci. 77:132–134. 2015. View Article : Google Scholar : PubMed/NCBI
28	Magerl M, Kauser S, Paus R and Tobin DJ: Simple and rapid method to isolate and culture follicular papillae from human scalp hair follicles. Exp Dermatol. 11:381–385. 2002. View Article : Google Scholar : PubMed/NCBI
29	Philpott MP, Sanders DA and Kealey T: Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro. J Invest Dermatol. 102:857–861. 1994. View Article : Google Scholar : PubMed/NCBI
30	Philpott MP, Green MR and Kealey T: Human hair growth in vitro. J Cell Sci. 97:463–471. 1990.PubMed/NCBI
31	Philpott MP, Sanders D, Westgate GE and Kealey T: Human hair growth in vitro: A model for the study of hair follicle biology. J Dermatol Sci. 7(Suppl): S55–S72. 1994. View Article : Google Scholar : PubMed/NCBI
32	Kim SN, Ha YW, Shin H, Son SH, Wu SJ and Kim YS: Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control. J Pharm Biomed Anal. 45:164–170. 2007. View Article : Google Scholar : PubMed/NCBI
33	Hall CL, Zhang H, Baile S, Ljungman M, Kuhstoss S and Keller ET: P21CIP-1/WAF-1 induction is required to inhibit prostate cancer growth elicited by deficient expression of the Wnt inhibitor Dickkopf-1. Cancer Res. 70:9916–9926. 2010. View Article : Google Scholar : PubMed/NCBI
34	Hirata H, Hinoda Y, Nakajima K, Kawamoto K, Kikuno N, Ueno K, Yamamura S, Zaman MS, Khatri G, Chen Y, et al: Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma. Int J Cancer. 128:1793–1803. 2011. View Article : Google Scholar
35	Lindner G, Botchkarev VA, Botchkareva NV, Ling G, van der Veen C and Paus R: Analysis of apoptosis during hair follicle regression (catagen). Am J Pathol. 151:1601–1617. 1997.PubMed/NCBI