Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2015 | Research article

Identification of a new plant extract for androgenic alopecia treatment using a non-radioactive human hair dermal papilla cell-based assay

Authors: Ruchy Jain, Orawan Monthakantirat, Parkpoom Tengamnuay, Wanchai De-Eknamkul

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

Login to get access

Abstract

Background

Androgenic alopecia (AGA) is a major type of human scalp hair loss, which is caused by two androgens: testosterone (T) and 5α-dihydrotestosterone (5α-DHT). Both androgens bind to the androgen receptor (AR) and induce androgen-sensitive genes within the human hair dermal papilla cells (HHDPCs), but 5α-DHT exhibits much higher binding affinity and potency than T does in inducing the involved androgen-sensitive genes. Changes in the induction of androgen-sensitive genes during AGA are caused by the over-production of 5α-DHT by the 5α-reductase (5α-R) enzyme; therefore, one possible method to treat AGA is to inhibit this enzymatic reaction.

Methods

RT-PCR was used to identify the presence of the 5α-R and AR within HHDPCs. A newly developed AGA-relevant HHDPC-based assay combined with non-radioactive thin layer chromatography (TLC) detection was used for screening crude plant extracts for the identification of new 5α-R inhibitors.

Results

HHDPCs expressed both 5α-R type 1 isoform of the enzyme (5α-R1) and AR in all of the passages used in this study. Among the thirty tested extracts, Avicennia marina (AM) displayed the highest inhibitory activity at the final concentration of 10 μg/ml, as the production of 5α-DHT decreased by 52 % (IC50 = 9.21 ± 0.38 μg/ml).

Conclusions

Avicennia marina (AM) was identified as a potential candidate for the treatment of AGA based on its 5α-R1-inhibitory activity.
Literature
1.
go back to reference Tobin DJ. The biogenesis and growth of human hair. In Hair in Toxicology—An Important Bio-Monitor, Tobin DJ, Editor. Cambridge: RSC Publishing; 2005. Tobin DJ. The biogenesis and growth of human hair. In Hair in Toxicology—An Important Bio-Monitor, Tobin DJ, Editor. Cambridge: RSC Publishing; 2005.
2.
go back to reference Stough D, Stenn K, Haber R, Parsley WM, Vogel JE, Whiting DA, et al. Psychological effect, pathophysiology, and management of androgenetic alopecia in men. Mayo Clin Proc. 2005;80(10):1316.CrossRefPubMed Stough D, Stenn K, Haber R, Parsley WM, Vogel JE, Whiting DA, et al. Psychological effect, pathophysiology, and management of androgenetic alopecia in men. Mayo Clin Proc. 2005;80(10):1316.CrossRefPubMed
3.
go back to reference Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002;2:1–11.CrossRef Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002;2:1–11.CrossRef
4.
6.
go back to reference Azzouni F, Godoy A, Li Y, Mohler J: The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol. 2012;Article ID 530121:18 pages Azzouni F, Godoy A, Li Y, Mohler J: The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol. 2012;Article ID 530121:18 pages
7.
go back to reference Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol. 2009;6:76–85.CrossRefPubMedPubMedCentral Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Clin Pract Urol. 2009;6:76–85.CrossRefPubMedPubMedCentral
8.
go back to reference Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, et al. Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J Invest Dermatol. 2007;128:262–9.CrossRefPubMed Kwack MH, Sung YK, Chung EJ, Im SU, Ahn JS, Kim MK, et al. Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes. J Invest Dermatol. 2007;128:262–9.CrossRefPubMed
9.
go back to reference Roh S-S, Kim CD, Lee M-H, Hwang S-L, Rang M-J, Yoon Y-K. The hair growth promoting effect of Sophora flavescens extract and its molecular regulation. J Dermatol Sci. 2002;30:43–9.CrossRefPubMed Roh S-S, Kim CD, Lee M-H, Hwang S-L, Rang M-J, Yoon Y-K. The hair growth promoting effect of Sophora flavescens extract and its molecular regulation. J Dermatol Sci. 2002;30:43–9.CrossRefPubMed
10.
go back to reference Botchkarev VA, Paus R. Molecular biology of hair morphogenesis: development and cycling. J Exp Zool B Mol Dev Evol. 2003;298:164–80.CrossRefPubMed Botchkarev VA, Paus R. Molecular biology of hair morphogenesis: development and cycling. J Exp Zool B Mol Dev Evol. 2003;298:164–80.CrossRefPubMed
11.
go back to reference Tsuboi R. Growth factors and hair growth. J Invest Dermatol. 1997;4:103–8. Tsuboi R. Growth factors and hair growth. J Invest Dermatol. 1997;4:103–8.
12.
go back to reference Randall VA. Androgens and human hair growth. Clin Endocrinol (Oxf). 1994;40:43.CrossRef Randall VA. Androgens and human hair growth. Clin Endocrinol (Oxf). 1994;40:43.CrossRef
13.
go back to reference Cotsarelis G, Millar SE. Towards a molecular understanding of hair loss and its treatment. Trends Mol Med. 2001;7:293–301.CrossRefPubMed Cotsarelis G, Millar SE. Towards a molecular understanding of hair loss and its treatment. Trends Mol Med. 2001;7:293–301.CrossRefPubMed
14.
go back to reference Rho S-S, Park S-J, Hwang S-L, Lee M-H, Kim CD, Lee I-H, et al. The hair growth promoting effect of Asiasari radix extract and its molecular regulation. J Dermatol Sci. 2005;38:89–97.CrossRefPubMed Rho S-S, Park S-J, Hwang S-L, Lee M-H, Kim CD, Lee I-H, et al. The hair growth promoting effect of Asiasari radix extract and its molecular regulation. J Dermatol Sci. 2005;38:89–97.CrossRefPubMed
15.
go back to reference Messenger AG. The control of hair growth: an overview. J Invest Dermatol. 1993;101(1 Suppl):4S–9S.CrossRefPubMed Messenger AG. The control of hair growth: an overview. J Invest Dermatol. 1993;101(1 Suppl):4S–9S.CrossRefPubMed
16.
go back to reference Hamada K, Thornton MJ, Laing I, Messenger AG, Randall VA. The Metabolism of Testosterone by Dermal Papilla Cells Cultured From Human Pubic and Axillary Hair Follicles Concurs with Hair Growth in 5α-Reductase Deficiency. J Invest Dermatol. 1996;106:1017–22.CrossRefPubMed Hamada K, Thornton MJ, Laing I, Messenger AG, Randall VA. The Metabolism of Testosterone by Dermal Papilla Cells Cultured From Human Pubic and Axillary Hair Follicles Concurs with Hair Growth in 5α-Reductase Deficiency. J Invest Dermatol. 1996;106:1017–22.CrossRefPubMed
17.
go back to reference Jain R, De-Eknamkul W. Potential targets in the discovery of new hair growth promoters of androgenic alopecia. Exp Opin Ther Targets. 2014;18(7):787–806.CrossRef Jain R, De-Eknamkul W. Potential targets in the discovery of new hair growth promoters of androgenic alopecia. Exp Opin Ther Targets. 2014;18(7):787–806.CrossRef
18.
go back to reference Meidan VM, Touitou E. Treatments for androgenetic alopecia and alopecia areata: current options and future prospects. Drugs. 2001;61:53–69.CrossRefPubMed Meidan VM, Touitou E. Treatments for androgenetic alopecia and alopecia areata: current options and future prospects. Drugs. 2001;61:53–69.CrossRefPubMed
19.
go back to reference Takahashi T, Kamimura A, Hamazono-Matsuoka T, Honda S. Phosphatidic acid has a potential to promote hair growth in vitro and in vivo, and activates mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in hair epithelial cells. J Invest Dermatol. 2003;121:448–56.CrossRefPubMed Takahashi T, Kamimura A, Hamazono-Matsuoka T, Honda S. Phosphatidic acid has a potential to promote hair growth in vitro and in vivo, and activates mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in hair epithelial cells. J Invest Dermatol. 2003;121:448–56.CrossRefPubMed
20.
go back to reference Iino M, Ehama R, Nakazawa Y, Iwabuchi T, Ogo M, Tajima M, et al. Adenosine stimulates fibroblast growth factor-7 gene expression via adenosine A2b receptor signaling in dermal papilla cells. J Invest Dermatol. 2007;127:1318–25.CrossRefPubMed Iino M, Ehama R, Nakazawa Y, Iwabuchi T, Ogo M, Tajima M, et al. Adenosine stimulates fibroblast growth factor-7 gene expression via adenosine A2b receptor signaling in dermal papilla cells. J Invest Dermatol. 2007;127:1318–25.CrossRefPubMed
21.
go back to reference Suraja R, Rejitha G, Anbu Jeba SB, Anandarajagopala K, Promwichita P. In vivo hair growth activity of Prunus dulcis seeds in rats. Biol Med. 2009;1:34–8. Suraja R, Rejitha G, Anbu Jeba SB, Anandarajagopala K, Promwichita P. In vivo hair growth activity of Prunus dulcis seeds in rats. Biol Med. 2009;1:34–8.
23.
go back to reference Kumar T, Chaiyasut C, Rungseevijitprapa W, Suttajit M. Screening of steroid 5α-reductase inhibitory activity and total phenolic content of Thai plants. J Med Plant Res. 2011;5:1265–71. Kumar T, Chaiyasut C, Rungseevijitprapa W, Suttajit M. Screening of steroid 5α-reductase inhibitory activity and total phenolic content of Thai plants. J Med Plant Res. 2011;5:1265–71.
24.
go back to reference Pandit S, Chauhan NS, Dixit V. Effect of Cuscuta reflexa Roxb on androgen-induced alopecia. J Cosmet Dermatol. 2008;7:199–204.CrossRefPubMed Pandit S, Chauhan NS, Dixit V. Effect of Cuscuta reflexa Roxb on androgen-induced alopecia. J Cosmet Dermatol. 2008;7:199–204.CrossRefPubMed
25.
go back to reference Raynaud J-P, Cousse H, Martin P-M. Inhibition of type 1 and type 2 5α-reductase activity by free fatty acids, active ingredients of Permixon®. J Steroid Biochem Mol Biol. 2002;82:233–9.CrossRefPubMed Raynaud J-P, Cousse H, Martin P-M. Inhibition of type 1 and type 2 5α-reductase activity by free fatty acids, active ingredients of Permixon®. J Steroid Biochem Mol Biol. 2002;82:233–9.CrossRefPubMed
26.
go back to reference Liu J, Kurashiki K, Shimizu K, Kondo R. Structure–activity relationship for inhibition of 5α-reductase by triterpenoids isolated from Ganoderma lucidum. Bioorg Med Chem. 2006;14:8654–60.CrossRefPubMed Liu J, Kurashiki K, Shimizu K, Kondo R. Structure–activity relationship for inhibition of 5α-reductase by triterpenoids isolated from Ganoderma lucidum. Bioorg Med Chem. 2006;14:8654–60.CrossRefPubMed
27.
go back to reference Murata K, Noguchi K, Kondo M, Onishi M, Watanabe N, Okamura K, et al. Inhibitory activities of Puerariae Flos against testosterone 5α-reductase and its hair growth promotion activities. J Nat Med. 2012;66:158–65.CrossRefPubMed Murata K, Noguchi K, Kondo M, Onishi M, Watanabe N, Okamura K, et al. Inhibitory activities of Puerariae Flos against testosterone 5α-reductase and its hair growth promotion activities. J Nat Med. 2012;66:158–65.CrossRefPubMed
28.
go back to reference Hiipakka RA, Zhang H-Z, Dai W, Dai Q, Liao S. Structure–activity relationships for inhibition of human 5α-reductases by polyphenols. Biochem Pharmacol. 2002;63:1165–76.CrossRefPubMed Hiipakka RA, Zhang H-Z, Dai W, Dai Q, Liao S. Structure–activity relationships for inhibition of human 5α-reductases by polyphenols. Biochem Pharmacol. 2002;63:1165–76.CrossRefPubMed
29.
go back to reference Kumar N, Rungseevijitprapa W, Narkkhong N-A, Suttajit M, Chaiyasut C. 5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment. J Ethnopharmacol. 2012;139:765–71.CrossRefPubMed Kumar N, Rungseevijitprapa W, Narkkhong N-A, Suttajit M, Chaiyasut C. 5α-reductase inhibition and hair growth promotion of some Thai plants traditionally used for hair treatment. J Ethnopharmacol. 2012;139:765–71.CrossRefPubMed
30.
go back to reference Matsuda H, Yamazaki M, Naruto S, Asanuma Y, Kubo M. Anti-androgenic and Hair Growth Promoting Activities of Lygodii Spora (Spore of Lygodium japonicum) I. Active Constituents Inhibiting Testosterone 5α-Reductase. Biol Pharm Bull. 2002;25:622–6.CrossRefPubMed Matsuda H, Yamazaki M, Naruto S, Asanuma Y, Kubo M. Anti-androgenic and Hair Growth Promoting Activities of Lygodii Spora (Spore of Lygodium japonicum) I. Active Constituents Inhibiting Testosterone 5α-Reductase. Biol Pharm Bull. 2002;25:622–6.CrossRefPubMed
31.
go back to reference Sawaya ME, Price VH. Different Levels of 5α-Reductase Type I and II, Aromatase, and Androgen Receptor in Hair Follicles of Women and Men with Androgenetic Alopecia. J Invest Dermatol. 1997;109:296–300.CrossRefPubMed Sawaya ME, Price VH. Different Levels of 5α-Reductase Type I and II, Aromatase, and Androgen Receptor in Hair Follicles of Women and Men with Androgenetic Alopecia. J Invest Dermatol. 1997;109:296–300.CrossRefPubMed
32.
go back to reference Bayne E, Flanagan J, Einstein M, Ayala J, Chang B, Azzolina B, et al. Immunohistochemical localization of types 1 and 2 5α-reductase in human scalp. Br J Dermatol. 1999;141:481–91.CrossRefPubMed Bayne E, Flanagan J, Einstein M, Ayala J, Chang B, Azzolina B, et al. Immunohistochemical localization of types 1 and 2 5α-reductase in human scalp. Br J Dermatol. 1999;141:481–91.CrossRefPubMed
33.
go back to reference Chen W, Orfanos C. The 5α-Reductase System and Its Inhibitors. Dermatology. 2009;193:177–84.CrossRef Chen W, Orfanos C. The 5α-Reductase System and Its Inhibitors. Dermatology. 2009;193:177–84.CrossRef
34.
go back to reference Zhu F, Chen X, Yuan Y, Huang M, Sun H, Xiang W. The chemical investigations of the mangrove plant Avicennia marina and its endophytes. Open Natural Products Journal. 2009;2:24–32.CrossRef Zhu F, Chen X, Yuan Y, Huang M, Sun H, Xiang W. The chemical investigations of the mangrove plant Avicennia marina and its endophytes. Open Natural Products Journal. 2009;2:24–32.CrossRef
Metadata
Title
Identification of a new plant extract for androgenic alopecia treatment using a non-radioactive human hair dermal papilla cell-based assay
Authors
Ruchy Jain
Orawan Monthakantirat
Parkpoom Tengamnuay
Wanchai De-Eknamkul
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1004-5

Other articles of this Issue 1/2016

BMC Complementary Medicine and Therapies 1/2016 Go to the issue