Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Flavonoid Silibinin Increases Hair-Inductive Property Via Akt and Wnt/β-Catenin Signaling Activation in 3-Dimensional-Spheroid Cultured Human Dermal Papilla Cells

  • Cheon, Hye In (Department of Dermatology, Konkuk University School of Medicine) ;
  • Bae, Seunghee (Research Institute for Molecular-Targeted Drugs, Department of Cosmetics Engineering, Konkuk University) ;
  • Ahn, Kyu Joong (Department of Dermatology, Konkuk University School of Medicine)
  • Received : 2018.10.26
  • Accepted : 2018.12.14
  • Published : 2019.02.28
Download PDF
⟨ Previous Next ⟩

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)/${\beta}$-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/${\beta}$-catenin signaling pathways in 3D DP spheroids. Silibinin can be a potential candidate to promote hair proliferation.

Keywords

References

  1. Singh RP, Agarwal R. 2009. Cosmeceuticals and silibinin. Clin. Dermatol. 27: 479-484. https://doi.org/10.1016/j.clindermatol.2009.05.012
  2. Singh RP, Agarwal R. 2002. Flavonoid antioxidant silymarin and skin cancer. Antioxid. Redox Signal. 4: 655-663. https://doi.org/10.1089/15230860260220166
  3. Singh RP, Dhanalakshmi S, Tyagi AK, Chan DC, Agarwal C, Agarwal R. 2002. Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels. Cancer Res. 62: 3063-3069.
  4. Singh RP, Deep G, Chittezhath M, Kaur M, Dwyer-Nield LD, Malkinson AM, et al. 2006. Effect of silibinin on the growth and progression of primary lung tumors in mice. J. Natl. Cancer Inst. 98: 846-855. https://doi.org/10.1093/jnci/djj231
  5. Lahiri-Chatterjee M, Katiyar SK, Mohan RR, Agarwal R. 1999. A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res. 59: 622-632.
  6. Zi X, Mukhtar H, Agarwal R. 1997. Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNF? Biochem. Biophys. Res. Commun. 239: 334-339. https://doi.org/10.1006/bbrc.1997.7375
  7. Choi B. 2018. Hair-growth potential of ginseng and its major metabolites: a review on its molecular mechanisms. Int. J. Mol. Sci. 19: 2703. https://doi.org/10.3390/ijms19092703
  8. Alonso L, Fuchs E. 2006. The hair cycle. J. Cell Sci. 119: 391-393. https://doi.org/10.1242/jcs.02793
  9. Westgate GE, Botchkareva NV, Tobin DJ. 2013. The biology of hair diversity. Int. J. Cosmetic Sci. 35: 329-336. https://doi.org/10.1111/ics.12041
  10. Santos Z, Avci P, Hamblin MR. 2015. Drug discovery for alopecia: gone today, hair tomorrow. Expert Opin. Drug Discov. 10: 269-292. https://doi.org/10.1517/17460441.2015.1009892
  11. Panteleyev AA. 2016. Putting the human hair follicle cycle on the map. J. Invest. Dermatol. 136: 4-6. https://doi.org/10.1016/j.jid.2015.10.052
  12. Porter RM. 2003. Mouse models for human hair loss disorders. J. Anat. 202: 125-131. https://doi.org/10.1046/j.1469-7580.2003.00140.x
  13. Topouzi H, Logan NJ, Williams G, Higgins CA. 2017. Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles. Exp. Dermatol. 26: 491-496. https://doi.org/10.1111/exd.13368
  14. Higgins CA, Chen JC, Cerise JE, Jahoda CAB, Christiano AM. 2013. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. Proc. Natl. Acad. Sci. USA. 110: 19679-19688. https://doi.org/10.1073/pnas.1309970110
  15. Higgins CA, Richardson GD, Ferdinando D, Westgate GE, Jahoda CAB. 2010. Modelling the hair follicle dermal papilla using spheroid cell cultures. Exp. Dermatol. 19: 546-548. https://doi.org/10.1111/j.1600-0625.2009.01007.x
  16. Greco V, Chen T, Rendl M, Schober M, Pasolli HA, Stokes N, et al. 2009. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 4: 155-169. https://doi.org/10.1016/j.stem.2008.12.009
  17. Yang C-C, Cotsarelis G. 2010. Review of hair follicle dermal cells. J. Dermatol. Sci. 57: 2-11. https://doi.org/10.1016/j.jdermsci.2009.11.005
  18. Zhou L, Yang K, Xu M, Andl T, Millar SE, Boyce S, et al. 2016. Activating $\beta$-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity. FEBS J. 283: 2823-2835. https://doi.org/10.1111/febs.13784
  19. Choi YM, An S, Lee J, Lee JH, Lee JN, Kim YS, et al. 2017. 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: 2323-2329. https://doi.org/10.1080/09168451.2017.1385383
  20. Manning BD, Toker A. 2017. AKT/PKB signaling: navigating the network. Cell 169: 381-405. https://doi.org/10.1016/j.cell.2017.04.001
  21. Alfonso M, Richter-Appelt H, Tosti A, Viera MS, Garcia M. 2005. The psychosocial impact of hair loss among men: a multinational European study. Curr. Med. Res. Opin. 21: 1829-1836. https://doi.org/10.1185/030079905X61820
  22. Upton JH, Hannen RF, Bahta AW, Farjo N, Farjo B, Philpott MP. 2015. Oxidative stress-associated senescence in dermal papilla cells of men with androgenetic alopecia. J. Invest. Dermatol. 135: 1244-1252. https://doi.org/10.1038/jid.2015.28
  23. Rastegar H, Ashtiani HA, Aghaei M, Barikbin B, Ehsani A. 2015. Herbal extracts induce dermal papilla cell proliferation of human hair follicles. Ann. Dermatol. 27:667-675. https://doi.org/10.5021/ad.2015.27.6.667
  24. Rho S , Park S , Hwang S , Lee M, Kim C, Lee I, et al. 2005. The hair growth promoting effect of extract and its molecular regulation. J. Dermatol. Sci. 38: 89-97. https://doi.org/10.1016/j.jdermsci.2004.12.025
  25. Woo H, Lee S, Kim S, Park D, Jung E. 2017. Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation. Arch. Dermatol. Res. 309: 381-388. https://doi.org/10.1007/s00403-017-1732-5
  26. Kang BM, Kwack MH, Kim MK, Kim JC, S ung YK. 2012. 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: 237-239. https://doi.org/10.1038/jid.2011.250
  27. de Lacharriere O, Deloche C, Misciali C, Piraccini BM, Vincenzi C, Bastien P, et al. 2001. Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Arch. Dermatol. 137: 641-646.
  28. Whiting DA. 2001. Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. J. Am. Acad. Dermatol. 45: S81-86. https://doi.org/10.1067/mjd.2001.117428
  29. Kishimoto J, Burgeson RE, Morgan BA. 2000. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 14: 1181-1185.
  30. Zhou D, Tan RJ, Fu H, Liu Y. 2015. Wnt/$\beta$-catenin signaling in kidney injury and repair: a double-edged sword. Lab. Invest. 96: 156-167. https://doi.org/10.1038/labinvest.2015.153
  31. Lu W, Lin C, King TD, Chen H, Reynolds RC, Li Y. 2012. Silibinin inhibits Wnt/$\beta$-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells. Cell. Signal. 24: 2291-2296. https://doi.org/10.1016/j.cellsig.2012.07.009
  32. Kim T, Oh S. 2012. Silybin synergizes with Wnt3a in activation of the Wnt/$\beta$-catenin signaling pathway through stabilization of intracellular $\beta$-catenin protein. Korean J. Microbiol. Biotechnol. 40: 50-56. https://doi.org/10.4014/kjmb.1202.02007
  33. Meidan VM, Touitou E. 2001. Treatments for androgenetic alopecia and alopecia areata: current options and future prospects. Drugs 61: 53-69. https://doi.org/10.2165/00003495-200161010-00006
  34. Dinh QQ, Sinclair R. 2007. Female pattern hair loss: current treatment concepts. Clin. Interv. Aging. 2: 189-199.
  35. Jain R, Monthakantirat O, Tengamnuay P, De-Eknamkul W. 2016. 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: 18.
  36. Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, et al. 2015. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci. Adv. 1: e1500973-e1500973. https://doi.org/10.1126/sciadv.1500973
  37. Murkute A, Sahu M, Mali P, Rangari V. 2010. Development and evaluation of formulations of microbial biotransformed extract of tobacco leaves for hair growth potential. Pharmacognosy Res. 2: 300-303. https://doi.org/10.4103/0976-4836.72328
  38. Bureau JP, Ginouves P, Guilbaud J, Roux ME. 2003. Essential oils and low-intensity electromagnetic pulses in the treatment of androgen-dependent alopecia. Adv. Ther. 20: 220-229. https://doi.org/10.1007/BF02850093

Cited by

  1. Protective Role of Nutritional Plants Containing Flavonoids in Hair Follicle Disruption: A Review vol.21, pp.2, 2019, https://doi.org/10.3390/ijms21020523
  2. Broussonetia papyrifera Promotes Hair Growth Through the Regulation of β-Catenin and STAT6 Target Proteins: A Phototrichogram Analysis of Clinical Samples vol.7, pp.2, 2019, https://doi.org/10.3390/cosmetics7020040
  3. Health Benefits of Silybum marianum: Phytochemistry, Pharmacology, and Applications vol.68, pp.42, 2019, https://doi.org/10.1021/acs.jafc.0c04791
  4. Indole Glycosides from Calanthe discolor with Proliferative Activity on Human Hair Follicle Dermal Papilla Cells vol.69, pp.5, 2021, https://doi.org/10.1248/cpb.c21-00006
  5. Gene expression profile of human follicle dermal papilla cells in response to Camellia japonica phytoplacenta extract vol.11, pp.3, 2019, https://doi.org/10.1002/2211-5463.13076
  6. Ent-kaurane-type diterpenoids from Isodonis Herba activate human hair follicle dermal papilla cells proliferation via the Akt/GSK-3β/β-catenin transduction pathway vol.75, pp.2, 2019, https://doi.org/10.1007/s11418-020-01477-8
  7. Ginsenoside Rg4 Enhances the Inductive Effects of Human Dermal Papilla Spheres on Hair Growth Via the AKT/GSK-3β/β-Catenin Signaling Pathway vol.31, pp.7, 2021, https://doi.org/10.4014/jmb.2101.01032
  8. A systematic summary of survival and death signalling during the life of hair follicle stem cells vol.12, pp.1, 2019, https://doi.org/10.1186/s13287-021-02527-y