RE-ORGA, a Korean Herb Extract, Can Prevent Hair Loss Induced by Dihydrotestosterone in Human Dermal Papilla Cells
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Background: Androgenic alopecia (AGA) is the most common type of hair loss. It is likely inherited genetically and is promoted by dihydrotestosterone. 5α-reductase has been proven a good target through finasteride use. However, the pathogenesis of AGA cannot be fully explained based only on dihydrotestosterone levels. Objective: To identify similar hairloss inhibition activity of RE-ORGA with mode of action other than finasteride. Methods: We prepared RE-ORGA from Korean herb mixtures. We performed MTT assays for cytotoxicity, Cell Counting Kit-8 assays for cell proliferation, and western blot to identify expression levels of 5α-reductase and Bax. RNA-sequencing was performed for the expression patterns of genes in dihydrotestosterone-activated pathways. Anti-inflammatory activity was also assessed by the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6. Results: REORGA could promote the proliferation of human dermal papilla cells and showed low cytotoxicity. It also inhibited the expression of 5α-reductases and Bax in the cells. RNA-sequencing results verified that the mRNA expressions of SRD5A1, Bax, transforming growth factor-beta 1 (TGF-β1), and TGF-β1 induced transcript 1 (TGFβ1I1) were decreased, whereas expression of protein tyrosine kinase 2 beta (PTK2β) was more elevated. REORGA also showed anti-inflammatory activity through decreased mRNA levels of TNF-α. Conclusion: Transcriptionally, up-regulation of PTK2β and concomitant down-regulation of TGFβ1I1 imply that RE-ORGA can modulate androgen receptor sensitivity, decreasing the expression of 5α-reductase type II and Bax together with TGF- β1 transcripts; RE-ORGA also showed partial anti-inflammatory activity. Overall, RE-ORGA is expected to alleviate hair loss by regulating 5α-reductase activity and the receptor’s androgen sensitivity.
Abstract
Background: Androgenic alopecia (AGA) is the most common type of hair loss. It is likely inherited genetically and is promoted by dihydrotestosterone. 5α-reductase has been proven a good target through finasteride use. However, the pathogenesis of AGA cannot be fully explained based only on dihydrotestosterone levels. Objective: To identify similar hairloss inhibition activity of RE-ORGA with mode of action other than finasteride. Methods: We prepared RE-ORGA from Korean herb mixtures. We performed MTT assays for cytotoxicity, Cell Counting Kit-8 assays for cell proliferation, and western blot to identify expression levels of 5α-reductase and Bax. RNA-sequencing was performed for the expression patterns of genes in dihydrotestosterone-activated pathways. Anti-inflammatory activity was also assessed by the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6. Results: REORGA could promote the proliferation of human dermal papilla cells and showed low cytotoxicity. It also inhibited the expression of 5α-reductases and Bax in the cells. RNA-sequencing results verified that the mRNA expressions of SRD5A1, Bax, transforming growth factor-beta 1 (TGF-β1), and TGF-β1 induced transcript 1 (TGFβ1I1) were decreased, whereas expression of protein tyrosine kinase 2 beta (PTK2β) was more elevated. REORGA also showed anti-inflammatory activity through decreased mRNA levels of TNF-α. Conclusion: Transcriptionally, up-regulation of PTK2β and concomitant down-regulation of TGFβ1I1 imply that RE-ORGA can modulate androgen receptor sensitivity, decreasing the expression of 5α-reductase type II and Bax together with TGF- β1 transcripts; RE-ORGA also showed partial anti-inflammatory activity. Overall, RE-ORGA is expected to alleviate hair loss by regulating 5α-reductase activity and the receptor’s androgen sensitivity.
참고문헌 (20)
- Courtois M, "Hair cycle and alopecia", Skin Pharmacol, 7, pp.84~89 (1994)
- Choudhry R, "Localization of androgen receptors in human skin by immunohistochemistry : implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands", J Endocrinol, 133, pp.467~475 (1992)
- Hibberts NA, "Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp", J Endocrinol, 156, pp.59~65 (1998)
- Sawaya ME, "Different levels of 5alpha-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia", J Invest Dermatol, 109, pp.296~300 (1997)
- Kaufman KD, "Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group", J Am Acad Dermatol, 39(4 Pt 1), pp.578~589 (1998)
- Schweikert HU, "Regulation of human hair growth by steroid hormones. II. Androstenedione metabolism in isolated hairs", J Clin Endocrinol Metab, 39, pp.1012~1019 (1974)
- Inui S, "Identification of androgen-inducible TGF-beta1 derived from dermal papilla cells as a key mediator in androgenetic alopecia", J Investig Dermatol Symp Proc, 8, pp.69~71 (2003)
- Kwack MH, "Dickkopf 1 promotes regression of hair follicles", J Invest Dermatol, 132, pp.1554~1560 (2012)
- Yu M, "Interleukin-6 cytokine family member oncostatin M is a hair-follicle-expressed factor with hair growth inhibitory properties", Exp Dermatol, 17, pp.12~19 (2008)
- Inui S, "Androgen receptor co-activator Hic-5", ARA55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles, 2007, pp.127, 2302~2306
- Kaliyadan F, "Androgenetic alopecia : an update", Indian J Dermatol Venereol Leprol, 79, pp.613~625 (2013)
- Kwack MH, "Dihydrotestosterone-inducible IL-6 inhibits elongation of human hair shafts by suppressing matrix cell proliferation and promotes regression of hair follicles in mice", J Invest Dermatol, 132, pp.43~49 (2012)
- Inui S, "Molecular basis of androgenetic alopecia : from androgen to paracrine mediators through dermal papilla", J Dermatol Sci, 61, pp.1~6 (2011)
- Uchiyama C, "Effects of Hura crepitans and its active ingredient, daphne factor F3, on dihydrotestosterone-induced neurotrophin-4 activation and hair retardation", Biol Pharm Bull, 35, pp.42~47 (2012)
- Upton JH, "Oxidative stress-associated senescence in dermal papilla cells of men with androgenetic alopecia", J Invest Dermatol, 135, pp.1244~1252 (2015)
- Audet-Walsh É, "Inverse regulation of DHT synthesis enzymes 5α-reductase types 1 and 2 by the androgen receptor in prostate cancer", Endocrinology, 158, pp.1015~1021 (2017)
- 신효승, "Induction of transforming growth factor-beta 1 by androgen is mediated by reactive oxygen species in hair follicle dermal papilla cells", BMB Reports, 46(9), pp.460~464 (2013), 생화학분자생물학회
- Hoffmann R, "The potential role of cytokines and T cells in alopecia areata", J Investig Dermatol Symp Proc, 4, pp.235~238 (1999)
- Philpott MP, "Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro : a possible role for interleukin-1 and tumour necrosis factor-alpha in alopecia areata", Br J Dermatol, 135, pp.942~948 (1996)
- Kasumagic-Halilovic E, "Tumor necrosis factor-alpha in patients with alopecia areata", Indian J Dermatol, 56, pp.494~496 (2011)