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http://dx.doi.org/10.4062/biomolther.2017.089

Oral Administration of Glycine and Leucine Dipeptides Improves Skin Hydration and Elasticity in UVB-Irradiated Hairless Mice  

Park, Jong Il (Department of Genetic Engineering & Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University)
Lee, Ji Eun (Department of Genetic Engineering & Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University)
Shin, Hyun Jun (Department of Genetic Engineering & Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University)
Song, Soonran (LG Household & Healthcare Research Park)
Lee, Won Kyung (LG Household & Healthcare Research Park)
Hwang, Jae Sung (Department of Genetic Engineering & Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.25, no.5, 2017 , pp. 528-534 More about this Journal
Abstract
Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.
Keywords
Gly-Leu; Leu-Gly; Hyaluronan; elasticity; Porcine placenta extract;
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1 Rock, K., Tigges, J., Sass, S., Schutze, A., Florea, A. M., Fender, A. C., Theis, F. J., Krutmann, J., Boege, F., Fritsche, E., Reifenberger, G. and Fischer, J. W. (2015) miR-23a-3p causes cellular senescence by targeting hyaluronan synthase 2: possible implication for skin aging. J. Invest. Dermatol. 135, 369-377.   DOI
2 Scharffetter-Kochanek, K., Brenneisen, P., Wenk, J., Herrmann, G., Ma, W., Kuhr, L., Meewes, C. and Wlaschek, M. (2000) Photoaging of the skin from phenotype to mechanisms. Exp. Gerontol. 35, 307-316.   DOI
3 Yoshikawa, C., Takano, F., Ishigaki, Y., Okada, M., KYO, S., Suzuki, N., Sugiura, K. and Koike, K. (2013) Effect of porcine placental extract on collagen production in human skin fibroblasts in vitro. Gynecol. Obstet. 3, 186.
4 Gschwandtner, M., Mildner, M., Mlitz, V., Gruber, F., Eckhart, L., Werfel, T., Gutzmer, R., Elias, P. M. and Tschachler, E. (2013) Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy 68, 37-47.   DOI
5 Bonte, F. (2011) Skin moisturization mechanisms: new data. Ann. Pharm. Fr. 69, 135-141.   DOI
6 Chyun, J. H. and Griminger, P. (1984) Improvement of nitrogen retention by arginine and glycine supplementation and its relation to collagen synthesis in traumatized mature and aged rats. J. Nutr. 114, 1697-1704.   DOI
7 Dai, G., Freudenberger, T., Zipper, P., Melchior, A., Grether-Beck, S., Rabausch, B., de Groot, J., Twarock, S., Hanenberg, H., Homey, B., Krutmann, J., Reifenberger, J. and Fischer, J. W. (2007) Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am. J. Pathol. 171, 1451-1461.   DOI
8 Gude, N. M., Roberts, C. T., Kalionis, B. and King, R. G. (2004) Growth and function of the normal human placenta. Thromb. Res. 114, 397-407.   DOI
9 Hsu, M. F. and Chiang, B. H. (2009) Stimulating effects of Bacillus subtilis natto-fermented Radix astragali on hyaluronic acid production in human skin cells. J. Ethnopharmacol. 125, 474-481.   DOI
10 Hong, K. B., Park, Y., Kim, J. H., Kim, J. M. and Suh, H. J. (2015) Effects of porcine placenta extract ingestion on ultraviolet B-induced skin damage in hairless mice. Korean J. Food Sci. Anim. Resour. 35, 413-420.   DOI
11 Jash, A., Kwon, H. K., Sahoo, A., Lee, C. G., So, J. S., Kim, J., Oh, Y. K., Kim, Y. B. and Im, S. H. (2011) Topical application of porcine placenta extract inhibits the progression of experimental contact hypersensitivity. J. Ethnopharmacol. 133, 654-662.   DOI
12 Kim, S., Kang, B. Y., Cho, S. Y., Sung, D. S., Chang, H. K., Yeom, M. H., Kim, D. H., Sim, Y. C. and Lee, Y. S. (2004) Compound K induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and increases hyaluronan in hairless mouse skin. Biochem. Biophys. Res. Commun. 316, 348-355.   DOI
13 Kogan, G., Soltes, L., Stern, R. and Gemeiner, P. (2007) Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol. Lett. 29, 17-25.
14 Kohl, E., Steinbauer, J., Landthaler, M. and Szeimies, R. M. (2011) Skin ageing. J. Eur. Acad. Dermatol. Venereol. 25, 873-884.   DOI
15 Nam, S. Y., Go, J. H., Lee, M., Kim, J., Jeong, H. and Lee, W. K. (2016) Anti-fatigue effect of fermented porcine placenta through the regulation of fatigue-associated inflammatory cytokines. Tang 6, 13.1-13.7.
16 Koike, K., Yamamoto, Y., Suzuki, N., Yamazaki, R., Yoshikawa, C., Takano, F., Takuma, K., Sugiura, K. and Inoue, M. (2013a) Efficacy of porcine placental extract on climacteric symptoms in peri- and postmenopausal women. Climacteric 16, 28-35.
17 Koike, K., Yamamoto, Y., Suzuki, N., Yamazaki, R., Yoshikawa, C., Takano, F., Sugiura, K. and Inoue, M. (2013b) Efficacy of porcine placental extract on shoulder stiffness in climacteric women. Climacteric 16, 447-452.   DOI
18 Koike, K., Yamamoto, Y., Suzuki, N., Yamazaki, R., Yoshikawa, C., Takuma, K., Sugiura, K. and Inoue, M. (2012) Efficacy of porcine placental extracts with hormone therapy for postmenopausal women with knee pain. Climacteric 15, 30-35.   DOI
19 Makrantonaki, E. and Zouboulis, C. C. (2007) Molecular mechanisms of skin aging: state of the art. Ann. N. Y. Acad. Sci. 1119, 40-50.   DOI
20 Matsumura, Y. and Ananthaswamy, H. N. (2004) Toxic effects of ultraviolet radiation on the skin. Toxicol. Appl. Pharmacol. 195, 298-308.   DOI
21 Nichols, J. A. and Katiyar, S. K. (2010) Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch. Dermatol. Res. 302, 71-83.   DOI
22 Watanabe, S., Togashi, S., Takahashi, N., and Fukui, T. (2002) L-tryptophan as an antioxidant in human placenta extract. J. Nutr. Sci. Vitaminol. 48, 36-39.   DOI
23 Suganuma, K., Nakajima, H., Ohtsuki, M. and Imokawa, G. (2010) Astaxanthin attenuates the UVA-induced up-regulation of matrixmetalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts. J. Dermatol. Sci. 58, 136-142.   DOI
24 Tobin, D. J. (2006) Biochemistry of human skin-our brain on the outside. Chem. Soc. Rev. 35, 52-67.   DOI
25 Togashi, S., Takahashi, N., Watanabe, S., Ishiguro, A. and Fukui, T. (2000) Suppressive effects of uracil, tyrosine, and phenylalanine contained in human-placenta extract on acute ethanol-induced liver injury in mice. J. Health Sci. 46, 126-131.   DOI
26 Wen, K. C., Lin, S. P., Yu, C. P. and Chiang, H. M. (2010) Comparison of Puerariae Radix and its hydrolysate on stimulation of hyaluronic acid production in NHEK cells. Am. J. Chin. Med. 38, 143-155.   DOI
27 Yoshikawa, C., Koike, K., Takano, F., Sugiur, K. and Suzuki, N. (2014) Efficacy of porcine placental extract on wrinkle widths below the eye in climacteric women. Climacteric 17, 370-376.   DOI
28 Rilla, K., Oikari, S., Jokela, T. A., Hyttinen, J. M., Karna, R., Tammi, R. H. and Tammi, M. I. (2013) Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS3. J. Biol. Chem. 288, 5973-5983.   DOI
29 Hahn, M. S., Kobler, J. B., Starcher, B. C., Zeitels, S. M. and Langer, R. (2006) Quantitative and comparative studies of the vocal fold extracellular matrix. I: Elastic fibers and hyaluronic acid. Ann. Otol. Rhinol. Laryngol. 115, 156-164.   DOI
30 Pal, P., Mallick, S., Mandal, S. K., Das, M., Dutta, A. K., Datta, P. K., Bera, R. and Bhadra, R. (2002) A human placental extract: in vivo and in vitro assessments of its melanocyte growth and pigmentinducing activities. Int. J. Dermatol. 41, 760-767.   DOI
31 Rock, K., Grandoch, M., Majora, M., Krutmann, J. and Fischer, J. W. (2011) Collagen fragments inhibit hyaluronan synthesis in skin fibroblasts in response to ultraviolet B (UVB): new insights into mechanisms of matrix remodeling. J. Biol. Chem. 286, 18268-18276.   DOI