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Research article

Clinical Microbiology and Biomedical Sciences

In Vivo Hair Growth Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid from Bacillus subtilis (Chungkookjang)

Jae-Chul Choi 1, 2, Hiroshi Uyama 3, Chul-Hoon Lee 4 and Moon-Hee Sung 1, 2*

1BioLeaders Corporation, Daejeon 305-500, Republic of Korea, 2Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea, 3Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan, 4Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Republic of Korea

Received: November 28, 2014; Accepted: December 11, 2014

J. Microbiol. Biotechnol. 2015; 25(3): 407-412

Published March 28, 2015 https://doi.org/10.4014/jmb.1411.11076

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

We investigated the effect of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) on hair loss in vitro and in vivo. 5-Alpha reductase is an enzyme that metabolizes the male hormone testosterone into dihydrotestosterone. By performing an in vitro experiment to analyze the inhibitory effects of UHMW γ-PGA on 5-alpha reductase activity, we determined that UHMW γ-PGA did in fact inhibit 5-alpha reductase activity, indicating the use of UHMW γ-PGA as a potential 5-alpha reductase inhibitor in the treatment of men with androgenetic alopecia. To evaluate the promotion of hair growth in vivo, we topically applied UHMW γ-PGA and minoxidil on the shaved dorsal skin of telogenic C57BL/6 mice for 4 weeks. At 4 weeks, the groups treated with UHMW γ-PGA showed hair growth on more than 50% of the shaved skin, whereas the control group showed less hair growth. To investigate the progression of hair follicles in the hair cycle, hematoxylin and eosin staining was performed. Histological observations revealed that the appearance of hair follicles was earlier in the UHMW γ-PGA-treated group than in the control group. The number of hair follicles on the relative area of shaved skin in the UHMW γ-PGA-treated group was higher than that observed on the shaved skin in the control group. These results indicate that UHMW γ-PGA can promote hair growth by effectively inducing the anagen phase in telogenic C57BL/6 mice.

Keywords

ultra-high molecular weight poly-γ-glutamic acid, hair growth, alopecia, 5-alpha reductase

References

  1. Adam ET, Tokarz D, Prent N, Cisek R, Alami J, Dumont DJ, et al. 2010. Nonlinear multicontrast microscopy of hematoxylinandeosin-stained histological sections. J. Biomed. Opt. 15: 026018.
    Pubmed CrossRef
  2. Ashiuchi M, Kamei T, Baek DH, Shin SY, Sung MH, Soda K, et al. 2001. Isolation of Bacillus subtilis (Chungkookjang), a poly-gamma-glutamate producer with high genetic competence. Appl. Microbiol. Biotechnol. 57: 764-769.
    Pubmed CrossRef
  3. D’Amico AV, Roehrborn CG. 2007. Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol. 8: 21-25.
    CrossRef
  4. Gelfuso GM, Gratieri T, Delgado-Charro MB, Guy RH, Vianna Lopez RF. 2013. Iontophoresis-targeted, follicular delivery of minoxidil sulfate for the treatment of alopecia. J. Pharm. Sci. 102: 1488-1494.
    Pubmed CrossRef
  5. Gordon KA, Tosti A. 2011. Alopecia: evaluation and treatment. Clin. Cosmet. Investig. Dermatol. 4: 101-106.
    Pubmed PMC CrossRef
  6. Gregoriou S, Papafragkaki D, Kontochristopoulos G, Rallis E, Kalogeromitros D, Rigopoulos D. 2010. Cytokines and other mediators in alopecia areata. Mediators Inflamm. 2010: 928030.
    Pubmed PMC CrossRef
  7. Hillmann K, Blume-Peytavi U. 2009. Diagnosis of hair disorders. Semin. Cutan. Med. Surg. 28: 33-38.
    Pubmed CrossRef
  8. Kaufman KD, Dawber RP. 1999. Finasteride, a Type 2 5 alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia. Expert Opin. Investig. Drugs 8: 403-415.
    Pubmed CrossRef
  9. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, et al. 2007. Oral administration of high molecular mass poly gamma-glutamate induces NK cell-mediated antitumor immunity. J. Immunol. 179: 775-780.
    Pubmed CrossRef
  10. Lee TY, Kim YH, Yoon SW, Choi JC, Yang JM, Kim CJ, et al. 2009. Oral administration of poly-gamma-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol. Immunother. 58: 1781-1794.
    Pubmed CrossRef
  11. Lim YT, Shim SM, Noh YW, Lee KS, Choi DY, Uyama H, et al. 2011. Bioderived polyelectrolyte nanogels for robust antigen loading and vaccine adjuvant effects. Small 7: 3281-3286.
    Pubmed CrossRef
  12. Moon HJ, Lee JS, Choi YK, Park JY, Talactac MR, Chowdhury MYE, et al. 2012. Induction of type I interferon by high-molecular poly-γ-glutamate protects B6.A2G-Mx1 mice against influenza A virus. Antiviral Res. 94: 98-102.
    Pubmed CrossRef
  13. Park C, Sung MH. 2009. New bioindustrial development of high molecular weight of poly-gamma-glutamic acid produced by Bacillus subtilis (Chungkookjang). Polym. Sci. Technol. 20: 440-446.
  14. Park HJ, Zhang N, Park DK. 2011. Topical application of Polygonum multiflorum extract induces hair growth of resting hair follicles through upregulating Shh and beta-catenin expression in C57BL/6 mice. J. Ethnopharmacol. 135: 369-375.
    Pubmed CrossRef
  15. Shi n HS, Lee JM, Park S Y. 2 013. H ai r growth a ctivity o f Crataegus pinnatifida on C57BL/6 mouse model. Phytother. Res. 27: 1352-1357.
    Pubmed
  16. Stefanato CM. 2010. Histopathology of alopecia: a clinicopathological approach to diagnosis. Histopathology 56:24-38.
    Pubmed CrossRef
  17. Stenn KS, Paus R. 2001. Controls of hair follicle cycling. Physiol. Rev. 71: 450-481.
  18. Sun ZY, Tu ZH. 1998. A novel in vitro model to screen steroid 5 alpha-reductase inhibitors against benign prostatic hyperplasia. Methods Find Exp. Clin. Pharmacol. 20: 283-287.
    Pubmed CrossRef
  19. Tarlow JK, Clay FE, Cork MJ. 1994. Severity of alopecia areata is associated with a polymorphism in the interleukin1 receptor antagonist gene. J. Invest. Dermatol. 103: 387-390.
    Pubmed CrossRef
  20. Tosti A, Piraccini BM, Sisti A, Duque-Estrada B. 2009. Hair loss in women. Minerva Ginecol. 61: 445-452.
    Pubmed
  21. Wosicka H, Cal K. 2010. Targeting to the hair follicles:current status and potential. J. Dermatol. Sci. 57: 83-89.
    Pubmed CrossRef
  22. Zhao J, Harada N, Okajima K. 2011. Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae. Growth Horm. IGF Res. 21: 260-267.
    Pubmed CrossRef

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Article

Research article

J. Microbiol. Biotechnol. 2015; 25(3): 407-412

Published online March 28, 2015 https://doi.org/10.4014/jmb.1411.11076

Copyright © The Korean Society for Microbiology and Biotechnology.

In Vivo Hair Growth Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid from Bacillus subtilis (Chungkookjang)

Jae-Chul Choi 1, 2, Hiroshi Uyama 3, Chul-Hoon Lee 4 and Moon-Hee Sung 1, 2*

1BioLeaders Corporation, Daejeon 305-500, Republic of Korea, 2Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea, 3Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan, 4Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Republic of Korea

Received: November 28, 2014; Accepted: December 11, 2014

Abstract

We investigated the effect of ultra-high molecular weight poly-γ-glutamic acid (UHMW
γ-PGA) on hair loss in vitro and in vivo. 5-Alpha reductase is an enzyme that metabolizes the
male hormone testosterone into dihydrotestosterone. By performing an in vitro experiment to
analyze the inhibitory effects of UHMW γ-PGA on 5-alpha reductase activity, we determined
that UHMW γ-PGA did in fact inhibit 5-alpha reductase activity, indicating the use of
UHMW γ-PGA as a potential 5-alpha reductase inhibitor in the treatment of men with
androgenetic alopecia. To evaluate the promotion of hair growth in vivo, we topically applied
UHMW γ-PGA and minoxidil on the shaved dorsal skin of telogenic C57BL/6 mice for
4 weeks. At 4 weeks, the groups treated with UHMW γ-PGA showed hair growth on more
than 50% of the shaved skin, whereas the control group showed less hair growth. To
investigate the progression of hair follicles in the hair cycle, hematoxylin and eosin staining
was performed. Histological observations revealed that the appearance of hair follicles was
earlier in the UHMW γ-PGA-treated group than in the control group. The number of hair
follicles on the relative area of shaved skin in the UHMW γ-PGA-treated group was higher
than that observed on the shaved skin in the control group. These results indicate that
UHMW γ-PGA can promote hair growth by effectively inducing the anagen phase in telogenic
C57BL/6 mice.

Keywords: ultra-high molecular weight poly-γ-glutamic acid, hair growth, alopecia, 5-alpha reductase

References

  1. Adam ET, Tokarz D, Prent N, Cisek R, Alami J, Dumont DJ, et al. 2010. Nonlinear multicontrast microscopy of hematoxylinandeosin-stained histological sections. J. Biomed. Opt. 15: 026018.
    Pubmed CrossRef
  2. Ashiuchi M, Kamei T, Baek DH, Shin SY, Sung MH, Soda K, et al. 2001. Isolation of Bacillus subtilis (Chungkookjang), a poly-gamma-glutamate producer with high genetic competence. Appl. Microbiol. Biotechnol. 57: 764-769.
    Pubmed CrossRef
  3. D’Amico AV, Roehrborn CG. 2007. Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial. Lancet Oncol. 8: 21-25.
    CrossRef
  4. Gelfuso GM, Gratieri T, Delgado-Charro MB, Guy RH, Vianna Lopez RF. 2013. Iontophoresis-targeted, follicular delivery of minoxidil sulfate for the treatment of alopecia. J. Pharm. Sci. 102: 1488-1494.
    Pubmed CrossRef
  5. Gordon KA, Tosti A. 2011. Alopecia: evaluation and treatment. Clin. Cosmet. Investig. Dermatol. 4: 101-106.
    Pubmed KoreaMed CrossRef
  6. Gregoriou S, Papafragkaki D, Kontochristopoulos G, Rallis E, Kalogeromitros D, Rigopoulos D. 2010. Cytokines and other mediators in alopecia areata. Mediators Inflamm. 2010: 928030.
    Pubmed KoreaMed CrossRef
  7. Hillmann K, Blume-Peytavi U. 2009. Diagnosis of hair disorders. Semin. Cutan. Med. Surg. 28: 33-38.
    Pubmed CrossRef
  8. Kaufman KD, Dawber RP. 1999. Finasteride, a Type 2 5 alpha-reductase inhibitor, in the treatment of men with androgenetic alopecia. Expert Opin. Investig. Drugs 8: 403-415.
    Pubmed CrossRef
  9. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, et al. 2007. Oral administration of high molecular mass poly gamma-glutamate induces NK cell-mediated antitumor immunity. J. Immunol. 179: 775-780.
    Pubmed CrossRef
  10. Lee TY, Kim YH, Yoon SW, Choi JC, Yang JM, Kim CJ, et al. 2009. Oral administration of poly-gamma-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol. Immunother. 58: 1781-1794.
    Pubmed CrossRef
  11. Lim YT, Shim SM, Noh YW, Lee KS, Choi DY, Uyama H, et al. 2011. Bioderived polyelectrolyte nanogels for robust antigen loading and vaccine adjuvant effects. Small 7: 3281-3286.
    Pubmed CrossRef
  12. Moon HJ, Lee JS, Choi YK, Park JY, Talactac MR, Chowdhury MYE, et al. 2012. Induction of type I interferon by high-molecular poly-γ-glutamate protects B6.A2G-Mx1 mice against influenza A virus. Antiviral Res. 94: 98-102.
    Pubmed CrossRef
  13. Park C, Sung MH. 2009. New bioindustrial development of high molecular weight of poly-gamma-glutamic acid produced by Bacillus subtilis (Chungkookjang). Polym. Sci. Technol. 20: 440-446.
  14. Park HJ, Zhang N, Park DK. 2011. Topical application of Polygonum multiflorum extract induces hair growth of resting hair follicles through upregulating Shh and beta-catenin expression in C57BL/6 mice. J. Ethnopharmacol. 135: 369-375.
    Pubmed CrossRef
  15. Shi n HS, Lee JM, Park S Y. 2 013. H ai r growth a ctivity o f Crataegus pinnatifida on C57BL/6 mouse model. Phytother. Res. 27: 1352-1357.
    Pubmed
  16. Stefanato CM. 2010. Histopathology of alopecia: a clinicopathological approach to diagnosis. Histopathology 56:24-38.
    Pubmed CrossRef
  17. Stenn KS, Paus R. 2001. Controls of hair follicle cycling. Physiol. Rev. 71: 450-481.
  18. Sun ZY, Tu ZH. 1998. A novel in vitro model to screen steroid 5 alpha-reductase inhibitors against benign prostatic hyperplasia. Methods Find Exp. Clin. Pharmacol. 20: 283-287.
    Pubmed CrossRef
  19. Tarlow JK, Clay FE, Cork MJ. 1994. Severity of alopecia areata is associated with a polymorphism in the interleukin1 receptor antagonist gene. J. Invest. Dermatol. 103: 387-390.
    Pubmed CrossRef
  20. Tosti A, Piraccini BM, Sisti A, Duque-Estrada B. 2009. Hair loss in women. Minerva Ginecol. 61: 445-452.
    Pubmed
  21. Wosicka H, Cal K. 2010. Targeting to the hair follicles:current status and potential. J. Dermatol. Sci. 57: 83-89.
    Pubmed CrossRef
  22. Zhao J, Harada N, Okajima K. 2011. Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae. Growth Horm. IGF Res. 21: 260-267.
    Pubmed CrossRef