Journal of the Korean Applied Science and Technology (한국응용과학기술학회지)

The Korean Society of Applied Science and Technology (한국응용과학기술학회)
권호 표지
DOI QR코드

DOI QR Code

A Study on the Use of Human Antibacterial Peptide LL-37-derived FK-13 as a Cosmetic Preservative

인간 항균펩타이드인 LL-37 유래의 FK-13의 화장품보존제로 활용에 대한 연구

  • Received : 2021.11.30
  • Accepted : 2021.12.27
  • Published : 2021.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Here, we conducted the study on the possibility of using FK-13, a short analog of human-derived antibacterial peptide LL-37, as a cosmetic preservative to discover a natural cosmetic preservative that is safe for human body. For the purpose, FK-13 composed of 13 amino acids was synthesized by solid-phase peptide synthesis, and purified using reversed phase-high performance liquid chromatography (RP-HPLC). The purity and molecular weight were confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis. FK-13 showed high antimicrobial activity on the three gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, and Staphylococcus epidermidis), the three gram-negative bacteria (Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa), and also even the fungus Candida glabrata. FK-13 had a broad spectrum of antibacterial activity, showing a suitability as a cosmetic preservative. In addition, FK-13 showed high thermostability and higher antibacterial activity in a comparative test with existing natural herbal cosmetic and chemical preservatives. Therefore, as FK-13 is a safe material and has high antibacterial activity at a low concentration, it is likely to be applied as a peptide natural cosmetic preservative that can replace existing chemical preservatives.

본 연구에서는 인체에 보다 안전한 천연 화장품보존제 발굴을 목표로 하여 인간유래 항균펩타이드 LL-37의 짧은 유사체인 FK-13을 화장품보존제로 사용하고자 연구를 진행하였다. 이를 위해 13개의 아미노산으로 구성된 FK-13 펩타이드를 고상 펩타이드 합성법로 합성하였고 reversed phase-high performance liquid chromatography (RP-HPLC)로 정제 후 liquid chromatography-mass spectrometry (LC-MS)를 이용하여 순도와 분자량을 확인하였다. 합성된 FK-13을 이용하여 미생물에 대한 방부력을 검정하였고 화장품에 적용 가능성을 살펴보았다. FK-13은 3개의 그람-양성균 (Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis)과 3개의 그람-음성균 (Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa), 그리고 진균인 Candida glabrata 에서도 높은 항균 활성을 보였으며 넓은 항균활성 스펙트럼을 나타내었다. 이를 바탕으로 화장품보존제로서의 적합성을 확인하였다. 또한 FK-13은 고온에서 분자의 열안정성을 보였으며 기존의 천연 한방화장품 방부제 및 화학보존제들과의 항균활성 비교 실험에서도 보다 월등한 항균활성 효능을 나타내었다. 따라서 FK-13 펩타이드는 인체 친화적이고 효과적인 항균활성을 나타내므로, 기존 화학보존제를 대체할 새로운 천연 화장품보존제로 적용이 가능할 것으로 판단된다.

Keywords

References

  1. E. J. Routledge, J. Parker, J. Odum, J. Ashby, and J. P. Sumpter, "Some alkyl hydroxy benzoate preservatives(parabens) are estrogenic", Toxicology and Applied Pharmacology, Vol. 153, pp. 12-19, (1998). https://doi.org/10.1006/taap.1998.8544
  2. J. Garcia-Gavin, R. Lissens, A. Timmermans, A, Goossens, "Allergic contact dermatitis caused by isopropyl alcohol: a missed allergen?", Contact Dermatitis, Vol. 65, pp. 101-106, (2011). https://doi.org/10.1111/j.1600-0536.2011.01936.x
  3. D. Lujan, B. Hernandez-Machin, Y. Penate, L Borrego, "Contact urticaria due to phenoxy ethanol in an after shave, Dermatitis, Vol. 20, E10, (2009).
  4. S. H. Mandy, "Contact dermatitis to substituted imidazolidinyl urea-a common preservative in cosmetics", Archives of Dermatology, Vol. 110, 463, (1974). https://doi.org/10.1001/archderm.1974.01630090089028
  5. P. D. Darbre, A. Aljarrah, W. R. Miller, N. G. Coldham, M. J. Sauer, G. S. Pope, "Concentrations of parabens in human breast tumours", Journal of Applied Toxicology, Vol. 24, pp. 5-13. (2004). https://doi.org/10.1002/jat.958
  6. Andersen. "Final report on the safety assessment of isobutylparaben and isopropylparaben", Journal of the American College of Toxicology, Vol. 14, pp. 364-372, (1995). https://doi.org/10.3109/10915819509083597
  7. T. Nishihara, J, Nishikawa, T. Kanayama, F. Dakeyama, K. Saito, M. Imagawa, "Estrogenic activities of 517 chemicals by yeast two-hybrid assay", Journal of Health Science, Vol. 46, pp. 282-298, (2000). https://doi.org/10.1248/jhs.46.282
  8. T. T. B. Vo, Y.-M. Yoo, K-C. Choi, E.-B. Jeung, "Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model", Reproductive Toxicology, Vol. 29. No. 3, pp. 306-316, (2010).
  9. T. Okubo, Y. Yokoyama, K. Kano, I. Kano, "ER-dependent estrogenic activity of parabens assessed by proliferation of human breast cancer MCF-7 cells and expression of ERα and ERβ and PR", Food and Chemical Toxicology, Vol. 39, pp. 1225-1232, (2001). https://doi.org/10.1016/S0278-6915(01)00073-4
  10. S.-H. Hwang, C.-H. Park, "Preservation of cosmetics by ethanol extract of Scutellaria baicalensis GEORGE", Korean Society of Biological Engineering, Vol. 24, No. 4, pp. 347-352, (2009).
  11. G. W. Ahn, M. H. Choi, Y. T. Woo, B. K. Jo, "A Study on the antimicrobial effect of glyceryl caprylate in cosmetics", Journal of Society of Cosmetic Scientists of Korea, Vol. 33, No. 1, pp. 47-52, (2007).
  12. N.-Y. Choi, "Assessment on antimicrobial activity of natural preservatives added to natural cosmetics", Inje University Master's Thesis, (2009).
  13. S.-H. Hwang, "Preservation of scutellariae radix extract for cosmetics", Kyung Hee University Master's Thesis, (2008).
  14. J.-E. Ku, H.-S. Han, J.-H. Song "The recent trend of the natural preservative used in cosmetics", Korean Journal of Aesthetics and Cosmetology, Vol. 11, No. 5, pp. 835-844, (2013).
  15. G. Rajasekaran, E. Y. Kim, S. Y. Shin, "LL-37-derived membrane-active FK-13 analogs possessing cell selectivity, anti-biofilm activity and synergy with chloramphenicol and Anti-inflammatory activity", Biochimica et Biophysica Acta, Biomembranes, Vol. 1859, No. 5, pp. 722-733, (2017). https://doi.org/10.1016/j.bbamem.2017.01.037
  16. X. Zhang, G. Bajic, G. R. Andersen, S. H. Christiansen, T. Vorup-Jensen, "The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis", Biochimica et Biophysica Acta. Proteins and Proteomics, Vol. 1864 No. 5 ,pp. 471-478, (2016). https://doi.org/10.1016/j.bbapap.2016.02.013
  17. J. M. Kahlenberg, M. J. Kaplan, "Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease", Journal of Immuology, Vol. 191. No. 10, pp. 4895-4901, (2013). https://doi.org/10.4049/jimmunol.1302005
  18. U. H. N. Durr, U. S. Sudheendra, A. Ramamoorthy, "LL-37, the only human member of the cathelicidin family of antimicrobial peptides", Biochimica et Biophysica Acta - Biomembranes, Vol. 1758, No. 9, pp. 1408-1425, (2006). https://doi.org/10.1016/j.bbamem.2006.03.030
  19. Ganesan Rajasekaran, Eun Young Kim, Song Yub Shin, "LL-37-derived membrane-active FK-13 analogs possessing cell selectivity, anti-biofilm activity and synergy with chloramphenicol and anti-inflammatory activity", Biochimica et Biophysica Acta - Biomembranes, Vol 1859 No. 5, pp. 722-733, (2017). https://doi.org/10.1016/j.bbamem.2017.01.037
  20. S. Galdiero, A. Falanga, R. Berisio, P. Grieco, G. Morelli, M. Galdiero, "Antimicrobial peptides as an opportunity against bacterial diseases", Current Medicinal Chemistry, Vol. 22, No. 14, pp. 1665-1677, (2015). https://doi.org/10.2174/0929867322666150311145632
  21. J. R. Edwin, P. Joanne, O. Jenny, A. John, P. S. John. "Some alkyl hydroxy benzoate preservatives (Parabens) are estrogenic", Toxicology and Applied Pharmacology, Vol. 153, pp. 12-19, (1998). https://doi.org/10.1006/taap.1998.8544
  22. A. A. Abdulghani, A. Gottlieb, A. Abdulghani, A. Sherr, S. Shirin, G. Solodkina, E. TAPIA, B. Wolf, A. B. Gottlieb, J. Abdulghani, V. Sherr "Effects of topical creams containing vitamin C, a copper-binding peptide cream and melatonin compared with tretinoin on the ultrastructure of normal skin", Disease Management and Clinical Outcomes, Vol. 1 No. 4, pp. 136-141, (1998). https://doi.org/10.1016/S1088-3371(98)00011-4
  23. K. Sakamoto, "Feature: Trends of peptides and applications to cosmetics World R&D trend for peptide in cosmetics." Fragrance journal, Vol. 36 No. 3, pp. 33-40, (2008).