Flavonoid Silibinin Increases Hair-Inductive Property Via Akt and Wnt/β-Catenin Signaling Activation in 3-Dimensional-Spheroid Cultured Human Dermal Papilla Cells
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초록
Hair loss, also known as alopecia, is a common dermatological condition of psychosocial significance; development of therapeutic candidates for the treatment of this condition is, hence, important. Silibinin, a secondary metabolite from Silybum marianum, is an effective antioxidant that also prevents various cutaneous problems. In this study, we have investigated the effect of silibinin on hair induction using three-dimensional (3D) cultured, human dermal papilla (DP) spheroids. Silibinin was found to significantly increase viability through AKT serine/threonine kinase (AKT) activation in 3D DP spheroids. This was correlated with an increase in the diameter of the 3D DP spheroids. The activation of the wingless and INT-1 (Wnt)/β-catenin signaling pathway, which is associated with hair growth induction in the DP, was evaluated using the T cell-specific transcription factor and lymphoid enhancer-binding factor (TCF/LEF) transcription factor reporter assay; results indicated significantly increased luciferase activity. In addition, we were able to demonstrate increased expression of the target genes, WNT5a and LEF1, using quantitative real-time PCR assay. Lastly, significantly elevated expression of signature genes associated with hair induction was demonstrated in the 3D DP spheroids treated with silibinin. These results suggest that silibinin promotes proliferation and hair induction through the AKT and Wnt/β-catenin signaling pathways in 3D DP spheroids. Silibinin can be a potential candidate to promote hair proliferation.
Abstract
Hair loss, also known as alopecia, is a common dermatological condition of psychosocial significance; development of therapeutic candidates for the treatment of this condition is, hence, important. Silibinin, a secondary metabolite from Silybum marianum, is an effective antioxidant that also prevents various cutaneous problems. In this study, we have investigated the effect of silibinin on hair induction using three-dimensional (3D) cultured, human dermal papilla (DP) spheroids. Silibinin was found to significantly increase viability through AKT serine/threonine kinase (AKT) activation in 3D DP spheroids. This was correlated with an increase in the diameter of the 3D DP spheroids. The activation of the wingless and INT-1 (Wnt)/β-catenin signaling pathway, which is associated with hair growth induction in the DP, was evaluated using the T cell-specific transcription factor and lymphoid enhancer-binding factor (TCF/LEF) transcription factor reporter assay; results indicated significantly increased luciferase activity. In addition, we were able to demonstrate increased expression of the target genes, WNT5a and LEF1, using quantitative real-time PCR assay. Lastly, significantly elevated expression of signature genes associated with hair induction was demonstrated in the 3D DP spheroids treated with silibinin. These results suggest that silibinin promotes proliferation and hair induction through the AKT and Wnt/β-catenin signaling pathways in 3D DP spheroids. Silibinin can be a potential candidate to promote hair proliferation.
참고문헌 (38)
- Singh RP, "Cosmeceuticals and silibinin", Clin. Dermatol, 27, pp.479~484 (2009)
- Singh RP, "Flavonoid antioxidant silymarin and skin cancer", Antioxid. Redox Signal, 4, pp.655~663 (2002)
- Singh RP, "Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factorbinding protein-3 levels", Cancer Res, 62, pp.3063~3069 (2002)
- Singh RP, "Effect of silibinin on the growth and progression of primary lung tumors in mice", J. Natl. Cancer Inst, 98, pp.846~855 (2006)
- Lahiri-Chatterjee M, "A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model", Cancer Res, 59, pp.622~632 (1999)
- Zi X, "Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin : inhibition of mRNA expression of an endogenous tumor promoter TNF? Biochem", Biophys. Res. Commun, 239, pp.334~339 (1997)
- Choi B, "Hair-growth potential of ginseng and its major metabolites: a review on its molecular mechanisms", Int. J. Mol. Sci, 19, pp.2703~ (2018)
- Alonso L, "The hair cycle", J. Cell Sci, 119, pp.391~393 (2006)
- Westgate GE, "The biology of hair diversity", Int. J. Cosmetic Sci, 35, pp.329~336 (2013)
- Santos Z, "Drug discovery for alopecia : gone today, hair tomorrow", Expert Opin. Drug Discov, 10, pp.269~292 (2015)
- Panteleyev AA, "Putting the human hair follicle cycle on the map", J. Invest. Dermatol, 136, pp.4~6 (2016)
- Porter RM, "Mouse models for human hair loss disorders", J. Anat, 202, pp.125~131 (2003)
- Topouzi H, "Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles", Exp. Dermatol, 26, pp.491~496 (2017)
- Higgins CA, "Microenvironmental reprogramming by threedimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth", Proc. Natl. Acad. Sci. USA, 110, pp.19679~19688 (2013)
- Higgins CA, "Modelling the hair follicle dermal papilla using spheroid cell cultures", Exp. Dermatol, 19, pp.546~548 (2010)
- Greco V, "A two-step mechanism for stem cell activation during hair regeneration", Cell Stem Cell, 4, pp.155~169 (2009)
- Yang C-C, "Review of hair follicle dermal cells", J. Dermatol. Sci, 57, pp.2~11 (2010)
- Zhou L, "Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity", FEBS J, 283, pp.2823~2835 (2016)
- Choi YM, "Titrated extract of Centella asiatica increases hair inductive property through inhibition of STAT signaling pathway in three-dimensional spheroid cultured human dermal papilla cells", Biosci. Biotechnol. Biochem, 81, pp.2323~2329 (2017)
- Manning BD, "AKT", PKB signaling : navigating the network, 2017, pp.169, 381~405
- Alfonso M, "The psychosocial impact of hair loss among men : a multinational European study", Curr. Med. Res. Opin, 21, pp.1829~1836 (2005)
- Upton JH, "Oxidative stress–associated senescence in dermal papilla cells of men with androgenetic alopecia", J. Invest. Dermatol, 135, pp.1244~1252 (2015)
- Hosein Rastegar, "Herbal Extracts Induce Dermal Papilla Cell Proliferation of Human Hair Follicles", Annals of Dermatology, 27(6), pp.667~675 (2015), 대한피부과학회
- Rho S, "The hair growth promoting effect of extract and its molecular regulation", J. Dermatol. Sci, 38, pp.89~97 (2005)
- Woo H, "Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation", Arch. Dermatol. Res, 309, pp.381~388 (2017)
- Kang BM, "Sphere formation increases the ability of cultured human dermal papilla cells to induce hair follicles from mouse epidermal cells in a reconstitution assay", J. Invest. Dermatol, 132, pp.237~239 (2012)
- de Lacharriere O, "Hair diameter diversity : a clinical sign reflecting the follicle miniaturization", Arch. Dermatol, 137, pp.641~646 (2001)
- Whiting DA, "Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss", J. Am. Acad. Dermatol, 45, pp.S81~S86 (2001)
- Kishimoto J, "Wnt signaling maintains the hair-inducing activity of the dermal papilla", Genes Dev, 14, pp.1181~1185 (2000)
- Zhou D, "Wnt", β-catenin signaling in kidney injury and repair : a double-edged sword, 2015, pp.96, 156~167
- Lu W, "Silibinin inhibits Wnt", β-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells, 2012, pp.24, 2291~2296
- Taeyeoun Kim, "Silybin Synergizes with Wnt3a in Activation of the Wnt", β-catenin Signaling Pathway through Stabilization of Intracellular β-Catenin Protein, 2012, pp.40(1), 50~56[DOI]
- Meidan VM, "Treatments for androgenetic alopecia and alopecia areata : current options and future prospects", Drugs, 61, pp.53~69 (2001)
- Dinh QQ, "Female pattern hair loss : current treatment concepts", Clin. Interv. Aging, 2, pp.189~199 (2007)
- Jain R, "Identification of a new plant extract for androgenic alopecia treatment using a non-radioactive human hair dermal papilla cell-based assay", BMC Complement. Altern. Med, 16, pp.18~ (2016)
- Harel S, "Pharmacologic inhibition of JAK-STAT signaling promotes hair growth", Sci. Adv, 1, pp.e1500973~e1500973 (2015)
- Murkute A, "Development and evaluation of formulations of microbial biotransformed extract of tobacco leaves for hair growth potential", Pharmacognosy Res, 2, pp.300~303 (2010)
- Bureau JP, "Essential oils and low-intensity electromagnetic pulses in the treatment of androgen-dependent alopecia", Adv. Ther, 20, pp.220~229 (2003)
