Journal of the Korea Academia-Industrial cooperation Society (한국산학기술학회논문지)

The Korea Academia-Industrial cooperation Society (한국산학기술학회)
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The Effects of Orally Administered Fermented Porcine Placenta and Its Major Dipeptides on UVB-induced Wrinkle Formation in the Hairless Mice

발효 돈태반과 그 주요 다이펩타이드 섭취가 UVB 조사에 의한 무모 생쥐의 피부 주름생성에 미치는 효과

  • Lee, JiEun (Department of Genetic engineering, Collage of Life Sciences, Kyung Hee University) ;
  • Park, Jongil (Department of Genetic engineering, Collage of Life Sciences, Kyung Hee University) ;
  • Kim, Jongbae (LG household & Healthcare Research Park) ;
  • Jeong, Hyein (LG household & Healthcare Research Park) ;
  • Hwang, JaeSung (Department of Genetic engineering, Collage of Life Sciences, Kyung Hee University)
  • 이지은 (경희대학교 생명공학원 유전공학과) ;
  • 박종일 (경희대학교 생명공학원 유전공학과) ;
  • 김종배 (LG생활건강 기술연구원) ;
  • 정혜인 (LG생활건강 기술연구원) ;
  • 황재성 (경희대학교 생명공학원 유전공학과)
  • Received : 2017.12.11
  • Accepted : 2018.03.09
  • Published : 2018.03.31
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Abstract

The effects of orally administered fermented porcine placenta (FPP) and its major dipeptides, L-Leucyl-Glycine (Leu-Gly) and Glycyl-L-Leucine (Gly-Leu), on UVB-induced wrinkle formation of the skin in hairless mice was studied. Treatment with FPP, Leu-Gly or Gly-Leu increased type I procollagen synthesis and decreased MMP-1 (matrix metalloproteinase-1) in human dermal fibroblast cells (HDF-N). Hairless mice were also exposed UVB irradiation three times a week and fermented porcine placenta extract (FPP), Leu-Gly and Gly-Leu was administered once a day for eight weeks. Daily intake of FPP, Leu-Gly and Gly-Leu for eight weeks decreased wrinkles, erythema and thickness of the skin and increased skin hydration and synthesis of collagen relative to a UVB-control. Moreover, FPP, Leu-Gly or Gly-Leu intake decreased the expression of MMP-3 and MMP-13 mRNA levels and inhibited activation of MMP-2 and MMP-9 induced by UVB irradiation in hairless mice skin. These results suggest that major dipeptides of the placenta, Leu-Gly and Gly-Leu have the potential for use as a functional food ingredient with anti-wrinkling properties.

본 연구에서는 발효 돈태반 (fermented porcine placenta, FPP)과 그의 주요 다이펩타이드인 L-Leucyl-Glycine (Leu-Gly), Glycyl-L-Leucine (Gly-Leu)의 섭취가 UVB 조사에 의한 무모 쥐의 피부 주름 생성에 미치는 효능을 알아보았다. Human Primary Dermal fibroblasts-Neonatal (HDF-N) 세포에서 세포 독성을 나타내지 않는 농도를 설정하여 평가하였을 때, FPP, Leu-Gly, Gly-Leu 처리 시 procollagen의 증가 및 MMP-1 (matrix metalloproteinase-1)의 감소를 확인하였다. 또한 무모 생쥐에 주 3회 UVB를 조사하여 광노화를 유도하였고, FPP 10, 100 mg/kg, Leu-Gly 10 mg/kg, Gly-Leu 10 mg/kg을 매일 총 8주간 경구투여 한 후, 주름생성, 홍반및 MMPs의 발현량을 측정하였다. 8주간 진행된 동물 실험 결과 UVB만 조사한 군과 비교하여 UVB를 조사하고 FPP, Leu-Gly, Gly-Leu을 섭취시킨 군에서 주름생성과 홍반이 감소하였고 피부 수분함량과 콜라겐 생합성이 증가하였다. 뿐만 아니라 FPP, Leu-Gly, Gly-Leu 섭취군에서 콜라겐 분해효소인 MMP-3, MMP-13의 mRNA 발현량이 감소하였고, MMP-2와 MMP-9의 활성이 감소하였다. 결과를 종합하였을 때, FPP의 주요 다이펩타이드인 Leu-Gly과 Gly-Leu은 자외선에 의한 주름 생성을 억제하고, 피부 손상을 회복시키는 효능을 갖는 피부미용식품 소재로서 활용 가능성이 클 것으로 사료된다.

Keywords

References

  1. M. Sand, T. Gambichler, D. Sand, M. Skrygan, P. Altmeyer and F.G. Bechara, "MicroRNAs and the skin: tiny players in the body's largest organ", J. Dermatol. Sci., vol. 53, no. 3, pp. 169-175, 2009. DOI: https://doi.org/10.1016/j.jdermsci.2008.10.004
  2. M. El‐Domyati, S. Attia, F. Saleh, D. Brown, D.E. Birk, F. Gasparro, H. Ahmad and J. Uitto, "Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin", Exp. Dermatol., vol. 11, no. 5, pp. 398-405, 2002. DOI: https://doi.org/10.1034/j.1600-0625.2002.110502.x
  3. J.Y. Lee, Y.K. Kim, J.Y. Seo, C.W. Choi, J.S. Hwang, B.G. Lee, I.S. Chang and J.H. Chung, "Loss of elastic fibers causes skin wrinkles in sun-damaged human skin", J. Dermatol. Sci., vol. 50, no. 2, pp. 99-107, 2008. DOI: https://doi.org/10.1016/j.jdermsci.2007.11.010
  4. K.K. Dong, N. Damaghi, S.D. Picart, N.G. Markova, K. Obayashi, Y. Okano, H. Masaki, S. Grether‐Beck, J. Krutmann and K.A. Smiles, "UV‐induced DNA damage initiates release of MMP-1 in human skin", Exp. Dermatol., vol. 17, no. 12, pp. 1037-1044, 2008. DOI: https://doi.org/10.1111/j.1600-0625.2008.00747.x
  5. C.E. Griffiths, T.S. Wang, T.A. Hamilton, J.J. Voorhees and C.N. Ellis, "A photonumeric scale for the assessment of cutaneous photodamage", Arch. Dermatol., vol. 128, no. 3, pp. 347-351, 1992. DOI: https://doi.org/10.1001/archderm.128.3.347
  6. G.L. Grove, M.J. Grove and J.J. Leyden, "Optical profilometry: an objective method for quantification of facial wrinkles", J. Am. Acad. Dermatol., vol. 21, no. 3, pp. 631-637, 1989. DOI: https://doi.org/10.1016/S0190-9622(89)70230-9
  7. S. Togashi, N. Takahashi, M. Iwama, S. Watanabe, K. Tamagawa and T. Fukui, "Antioxidative collagen-derived peptides in human-placenta extract", Placenta, vol. 23, no. 6, pp. 497-502, 2002. DOI: https://doi.org/10.1053/plac.2002.0833
  8. M. Yeom, H. Lee, G. Kim, I. Shim, H. Lee and D. Hahm, "Therapeutic effects of Hominis placenta injection into an acupuncture point on the inflammatory responses in subchondral bone region of adjuvant-induced polyarthritic rat", Biological and Pharmaceutical Bulletin, vol. 26, no. 10, pp. 1472-1477, 2003. DOI: https://doi.org/10.1248/bpb.26.1472
  9. T.K. Biswas, B. Auddy, N.P. Bhattacharya, S. Bhattacharya and B. Mukherjee, "Wound healing activity of human placental extracts in rats.", Acta Pharmacol.Sin., vol. 22, no. 12, pp. 1113-1116, 2001.
  10. M. Kawakatsu, Y. Urata, S. Goto, Y. Ono and T. Li, "Placental extract protects bone marrow-derived stem/progenitor cells against radiation injury through anti-inflammatory activity", J. Radiat.Res., vol. 54, no. 2, pp. 268-276, 2012. DOI: https://doi.org/10.1093/jrr/rrs105
  11. S. Togashi, N. Takahashi, Y. Kubo, A. Shigihara, K. Higashiyama, S. Watanabe and T. Fukui, "Purification and identification of antioxidant substances in human-placenta extracts", J. Health Sci., vol. 46, no. 2, pp. 117-125, 2000. DOI: https://doi.org/10.1248/jhs.46.117
  12. MFDS. Food Code. Ministry of Food and Drug Safety, Cheongju, Korea 2016.
  13. J.W. Hong, W.J. Lee, S.B. Hahn, B.J. Kim and D.H. Lew, "The effect of human placenta extract in a wound healing model", Ann. Plast. Surg., vol. 65, no. 1, pp. 96-100, 2010. DOI: https://doi.org/10.1097/SAP.0b013e3181b0bb67
  14. D. Zhang, G. Lijuan, L. Jingjie, L. Zheng, C. Wang, Z. Wang, L. Liu, L. Mira and C. Sung, "Cow placenta extract promotes murine hair growth through enhancing the insulin-like growth factor-1", Indian J. Dermatol., vol. 56, no. 1, pp. 14, 2011. DOI: https://doi.org/10.4103/0019-5154.77544
  15. J. Jung, H. Lee, J.M. Lee, K. Na, S. Hwang and G.J. Kim, "Placenta extract promote liver regeneration in CCl 4-injured liver rat model", Int. Immunopharmacol., vol. 11, no. 8, pp. 976-984, 2011. DOI: https://doi.org/10.1016/j.intimp.2011.02.012
  16. K. Hong, Y. Park, J.H. Kim, J.M. Kim and H.J. Suh, "Effects of porcine placenta extract ingestion on ultraviolet B-induced skin damage in hairless mice", Korean Journal for Food Science of Animal Resources, vol. 35, no. 3, pp. 413, 2015. DOI: https://doi.org/10.5851/kosfa.2015.35.3.413
  17. S. Nam, H. Kim and H. Jeong, "Anti-fatigue effect by active dipeptides of fermented porcine placenta through inhibiting the inflammatory and oxidative reactions", Biomedicine & Pharmacotherapy, vol. 84, pp. 51-59, 2016. DOI: https://doi.org/10.1016/j.biopha.2016.09.012
  18. S. Nam, J. Go, M. Lee, J. Kim, H. Jeong and W.K. Lee, "Anti-fatigue effect of fermented porcine placenta through the regulation of fatigue-associated inflammatory cytokines", Tang, vol. 6, no. 2, pp. 13.7, 2016. DOI: http://dx.doi.org/10.5667/tang.2016.0011
  19. S. Reagan-Shaw, M. Nihal and N. Ahmad, "Dose translation from animal to human studies revisited", The FASEB journal, vol. 22, no. 3, pp. 659-661, 2008. DOI: https://doi.org/10.1096/fj.07-9574LSF
  20. B.A. Booth, K.L. Polak and J. Uitto, "Collagen biosynthesis by human skin fibroblasts. I. Optimization of the culture conditions for synthesis of type I and type III procollagens", Biochimica et Biophysica Acta (BBA)-Nucleic Acids and Protein Synthesis, vol. 607, no. 1, pp. 145-160, 1980. https://doi.org/10.1016/0005-2787(80)90228-2
  21. Y. Park, B.K. Han, H. Choi, Y.H. Hong, E.Y. Jung and H.J. Suh, "Effect of porcine placenta extract from subcritical water extraction on photodamage in human keratinocytes", Korean Journal for Food Science of Animal Resources, vol. 35, no. 2, pp. 164, 2015. DOI: https://doi.org/10.5851/kosfa.2015.35.2.164
  22. H. Nagase and J.F. Woessner Jr, "Matrix metalloproteinases", J Biol Chem 274 (31): 21491- 21494", Find this article online, 1999. https://doi.org/10.1074/jbc.274.31.21491
  23. M. Brennan, H. Bhatti, K.C. Nerusu, N. Bhagavathula, S. Kang, G.J. Fisher, J. Varani and J.J. Voorhees, "Matrix metalloproteinase‐1 is the major collagenolytic enzyme responsible for collagen damage in UVirradiated human skin", Photochem. Photobiol., vol. 78, no. 1, pp. 43-48, 2003. DOI: https://doi.org/10.1562/0031-8655(2003)0780043 MMITMC2.0.CO2
  24. W.D. Shingleton, A.J. Ellis, A.D. Rowan and T.E. Cawston, "Retinoic acid combines with interleukin‐1 to promote the degradation of collagen from bovine nasal cartilage: Matrix metalloproteinases‐1 and‐13 are involved in cartilage collagen breakdown", J. Cell. Biochem., vol. 79, no. 4, pp. 519-531, 2000. DOI: https://doi.org/10.1002/1097-4644(20001215)79:4 <519::AID-JCB10>3.0.CO;2-U
  25. K. Scharffetter-Kochanek, P. Brenneisen, J. Wenk, G. Herrmann, W. Ma, L. Kuhr, C. Meewes and M. Wlaschek, "Photoaging of the skin from phenotype to mechanisms", Exp. Gerontol., vol. 35, no. 3, pp. 307-316, 2000. DOI: https://doi.org/10.1016/S0531-5565(00)00098-X
  26. J. Chyun and P. Griminger, "Improvement of nitrogen retention by arginine and glycine supplementation and its relation to collagen synthesis in traumatized mature and aged rats", J. Nutr., vol. 114, no. 9, pp. 1697-1704, 1984. DOI: https://doi.org/10.1093/jn/114.9.1697
  27. A.M.M. Jais, R. McCulloch and K. Croft, "Fatty acid and amino acid composition in haruan as a potential role in wound healing", General Pharmacology: The Vascular System, vol. 25, no. 5, pp. 947-950, 1994. DOI: https://doi.org/10.1016/0306-3623(94)90101-5
  28. S. Park, J. Lee, J. Jeon and H. Byun, "Characterization of a collagenase-1 inhibitory peptide purified from skate dipturus chilensis skin", Korean Journal of Fisheries and Aquatic Sciences, vol. 44, no. 5, pp. 456-463, 2011. DOI: https://doi.org/10.5657/KFAS.2011.0456
  29. J.I. Park, J.E. Lee, H.J. Shin, S. Song, W.K. Lee and J.S. Hwang, "Oral Administration of Glycine and Leucine Dipeptides Improves Skin Hydration and Elasticity in UVB-Irradiated Hairless Mice", Biomolecules & therapeutics, vol. 25, no. 5, pp. 528, 2017. DOI: https://doi.org/10.4062/biomolther.2017.089
  30. K.J. Park, S.H. Park and J.K. Kim, "Anti-wrinkle Activity of Acanthopanax senticosus Extract in Ultraviolet B (UVB)-induced Photoaging", J Korean Soc Food Sci Nutr., vol. 39, no. 1, pp. 42-46, 2010. DOI: https://doi.org/10.3746/jkfn.2010.39.1.042
  31. H. Shin, J. il Park, C. Kwon, H. young Kim, N. Inoue, K. Seiko and J.S. Hwang, "The Effect of Collagen Peptide Intake on UVB-induced Skin Damage in Hairless mice", Journal of the Korea Academia-Industrial cooperation Society, vol. 17, no. 3, pp. 611-621, 2016. DOI: https://doi.org/10.5762/KAIS.2016.17.3.611