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The In Vivo and In Vitro Effects of Terminalia bellirica (Gaertn.) Roxb. Fruit Extract on Testosterone-Induced Hair Loss

  • Min Jeong Woo (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Ha Yeong Kang (School of Food Science and Biotechnology, Kyungpook National University) ;
  • So Jeong Paik (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Hee Jung Choi (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Salah Uddin (Ethnobotanical Database of Bangladesh (EDB)) ;
  • Sangwoo Lee (International Biological Material Research Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Soo-Yong Kim (International Biological Material Research Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Sangho Choi (International Biological Material Research Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Sung Keun Jung (School of Food Science and Biotechnology, Kyungpook National University)
  • Received : 2023.06.05
  • Accepted : 2023.07.12
  • Published : 2023.11.28

Abstract

Due to the continuous increase in patients with androgenetic alopecia (AGA) and psychological disorders such as depression and anxiety, the demand for hair loss treatment and effective hair growth materials has increased. Terminalia bellirica (Gaertn.) Roxb. (TBE) reportedly exerts anti-inflammatory, hepatoprotective, and antidiabetic effects, among others, but its effects on testosterone (TS)-inhibited hair growth remains unclear. In this study, we evaluated the effects of TBE on TS-induced hair growth regression in human follicle dermal papilla cells (HFDPCs) and C57BL/6 mice. Oral administration of TBE increased TS-induced hair growth retardation. Interestingly, effects were greater when compared with finasteride, a commercial hair loss treatment product. Histological analyses revealed that oral TBE administration increased hair follicles in the dorsal skin of C57BL/6 mice. Additionally, western blotting and immunofluorescence showed that oral TBE administration recovered the TS-induced inhibition of cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki67 expression in vivo. Using in vitro proliferation assays, TBE promoted HFDPC growth, which was suppressed by TS treatment. Thus, TBE may be a promising nutraceutical for hair health as it promoted hair growth in AGA-like in vitro and in vivo models.

Keywords

Acknowledgement

This study was supported by the Korea Research Institute of Bioscience & Biotechnology Initiative Program of the Republic of Korea.

References

  1. Houschyar KS, Borrelli MR, Tapking C, Popp D, Puladi B, Ooms M, et al. 2020. Molecular mechanisms of hair growth and regeneration: Current understanding and novel paradigms. Dermatology 236: 271-280. 
  2. Hardy MH. 1992. The secret life of the hair follicle. Trends Genet. 8: 55-61. 
  3. Wolfram LJ. 2003. Human hair: a unique physicochemical composite. J. Am. Acad. Dermatol. 48: S106-114. 
  4. Natarelli N, Gahoonia N, Sivamani RK. 2023. Integrative and mechanistic approach to the hair growth cycle and hair loss. J. Clin. Med. 12: 893. 
  5. Alessandrini A, Bruni F, Piraccini BM, Starace M. 2021. Common causes of hair loss - clinical manifestations, trichoscopy and therapy. J. Eur. Acad. Dermatol. Venereol. 35: 629-640. 
  6. Dhariwala MY, Ravikumar P. 2019. An overview of herbal alternatives in androgenetic alopecia. J. Cosmet. Dermatol. 18: 966-975. 
  7. Phillips TG, Slomiany WP, Allison R. 2017. Hair loss: Common causes and treatment. Am. Fam. Physician 96: 371-378. 
  8. Wang H, Pan L, Wu Y. 2022. Epidemiological trends in alopecia areata at the global, regional, and national levels. Front. Immunol. 13: 874677. 
  9. Aukerman EL, Jafferany M. 2023. The psychological consequences of androgenetic alopecia: a systematic review. J. Cosmet. Dermatol. 22: 89-95. 
  10. Fu D, Huang J, Li K, Chen Y, He Y, Sun Y, et al. 2021. Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia. Biomed. Pharmacother. 137: 111247. 
  11. Leiros GJ, Ceruti JM, Castellanos ML, Kusinsky AG, Balana ME. 2017. Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia. Mol. Cell. Endocrinol. 439: 26-34. 
  12. Gentile P, Garcovich S. 2019. Advances in regenerative stem cell therapy in androgenic alopecia and hair loss: Wnt pathway, growth-factor, and mesenchymal stem cell signaling impact analysis on cell growth and hair follicle development. Cells 8: 466. 
  13. Nestor MS, Ablon G, Gade A, Han H, Fischer DL. 2021. Treatment options for androgenetic alopecia: efficacy, side effects, compliance, financial considerations, and ethics. J. Cosmet. Dermatol. 20: 3759-3781. 
  14. Gupta A, Kumar R, Bhattacharyya P, Bishayee A, Pandey AK. 2020. Terminalia bellirica (Gaertn.) roxb. (Bahera) in health and disease: a systematic and comprehensive review. Phytomedicine 77: 153278. 
  15. Tanaka M, Kishimoto Y, Sasaki M, Sato A, Kamiya T, Kondo K, et al. 2018. Terminalia bellirica (Gaertn.) Roxb. extract and gallic acid attenuate LPS-induced inflammation and oxidative stress via MAPK/NF-κB and Akt/AMPK/Nrf2 pathways. Oxid. Med. Cell Longev. 2018: 9364364. 
  16. Kuriakose J, Lal Raisa H, A V, Eldhose B, M SL. 2017. Terminalia bellirica (Gaertn.) Roxb. fruit mitigates CCl(4) induced oxidative stress and hepatotoxicity in rats. Biomed. Pharmacother. 93: 327-333. 
  17. Suryavanshi SV, Barve K, Addepalli V, Utpat SV, Kulkarni YA. 2021. Triphala churna-A traditional formulation in ayurveda mitigates diabetic neuropathy in rats. Front. Pharmacol. 12: 662000. 
  18. Ke J, Guan H, Li S, Xu L, Zhang L, Yan Y. 2015. Erbium: YAG laser (2,940 nm) treatment stimulates hair growth through upregulating Wnt 10b and β-catenin expression in C57BL/6 mice. Int. J. Clin. Exp. Med. 8: 20883-20889. 
  19. Inui S, Itami S. 2011. Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla. J. Dermatol. Sci. 61: 1-6. 
  20. Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Lleres D, et al. 2016. The cell proliferation antigen Ki-67 organises heterochromatin. Elife 5: e13722. 
  21. Muller-Rover S, Foitzik K, Paus R, Handjiski B, van der Veen C, Eichmuller S, et al. 2001. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J. Invest. Dermatol. 117: 3-15. 
  22. Elliott K, Messenger AG, Stephenson TJ. 1999. Differences in hair follicle dermal papilla volume are due to extracellular matrix volume and cell number: implications for the control of hair follicle size and androgen responses. J. Invest. Dermatol. 113: 873-875. 
  23. Ring C, Heitmiller K, Correia E, Gabriel Z, Saedi N. 2022. Nutraceuticals for androgenetic alopecia. J. Clin. Aesthet. Dermatol. 15: 26-29. 
  24. Abdin R, Zhang Y, Jimenez JJ. 2022. Treatment of androgenetic alopecia using PRP to target dysregulated mechanisms and pathways. Front. Med (Lausanne). 9: 843127. 
  25. Hamilton JB. 1951. Patterned loss of hair in man; types and incidence. Ann. NY Acad. Sci. 53: 708-728. 
  26. Lee S, Lee YB, Choe SJ, Lee WS. 2019. Adverse sexual effects of treatment with finasteride or dutasteride for male androgenetic alopecia: a systematic review and meta-analysis. Acta Derm. Venereol. 99: 12-17. 
  27. Shin DW. 2022. The molecular mechanism of natural products activating Wnt/β-catenin signaling pathway for improving hair loss. Life (Basel). 12: 1856. 
  28. Zhu HL, Gao YH, Yang JQ, Li JB, Gao J. 2018. Serenoa repens extracts promote hair regeneration and repair of hair loss mouse models by activating TGF-β and mitochondrial signaling pathway. Eur. Rev. Med. Pharmacol. Sci. 22: 4000-4008. 
  29. Ellis T, Smyth I, Riley E, Bowles J, Adolphe C, Rothnagel JA, et al. 2003. Overexpression of sonic hedgehog suppresses embryonic hair follicle morphogenesis. Dev. Biol. 263: 203-215. 
  30. Choi BY. 2020. Targeting Wnt/β-catenin pathway for developing therapies for hair loss. Int. J. Mol. Sci. 21: 4915. 
  31. Papukashvili D, Rcheulishvili N, Liu C, Xie F, Tyagi D, He Y, et al. 2021. Perspectives on miRNAs targeting DKK1 for developing hair regeneration therapy. Cells 10: 2957. 
  32. Lin GL, Hankenson KD. 2011. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell. Biochem. 112: 3491-501.