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별불가사리로부터 분리된 Asterosaponin P1의 항노화 효능

Anti-aging Effect of Asterosaponin P1 Isolated from Asterina pectinifera

  • Jin, Mu Hyun (Skin Research Center, R&D Park, LG Household & Health Care, Ltd.) ;
  • Lee, So Young (Skin Research Center, R&D Park, LG Household & Health Care, Ltd.) ;
  • Yeo, Hyerin (Skin Research Center, R&D Park, LG Household & Health Care, Ltd.) ;
  • Kim, Hyo Jin (Skin Research Center, R&D Park, LG Household & Health Care, Ltd.) ;
  • Chang, Yun Hee (Skin Research Center, R&D Park, LG Household & Health Care, Ltd.)
  • 투고 : 2018.09.03
  • 심사 : 2018.10.16
  • 발행 : 2018.12.30

초록

별불가사리(Asterina pectinifera Muller and Troschel)는 우리나라 전국 연안에서 흔히 볼 수 있는 토속종으로, 패류 양식장에 피해를 주는 불가사리류 중의 하나이다. 별불가사리 퇴치를 위해 대부분 건조하여 비료로 활용하고 있으며, 고부가가치 창출을 위한 다양한 연구가 진행되었으나 실제 활용은 미미한 실정이다. 따라서, 별불가사리로부터 피부 유용성분을 밝혀 새로운 활용 방안을 모색하고자 하였다. 성분연구를 통해 별불가사리로 부터 2종의 polyhydroxysteroid와 1종의 saponin을 분리하였으며, 이의 구조를 각각 $5{\alpha}$-cholestane-$3{\beta},6{\alpha},7{\alpha},8,15{\alpha},16{\beta},26$-heptol, $5{\alpha}$-cholestane-$3{\beta},4{\beta},6{\alpha},7{\alpha},8,15{\beta},16{\beta},2$6-octol 및 asterosaponin $P_1$으로 동정하였다. 이 물질들의 피부 효능을 확인한 결과 asterosaponin $P_1$이 표피 줄기세포의 증식을 촉진시키고, 각질형성세포에서 히알루론산을 합성하는 효소인 hyaluronan synthase-2와 hyaluronan synthase-3 유전자의 발현을 증가시킴을 확인하였다. 또한, asterosaponin $P_1$은 섬유아세포에서 진피의 주요 콜라겐인 type 1 콜라겐의 생합성을 촉진하는 효능을 보였다. 이상의 결과들로부터, 별불가사리로부터 분리한 asterosaponin $P_1$은 노화에 동반되는 피부 증상을 개선하는 항노화 화장품 소재로 활용될 수 있을 것으로 판단된다.

The starfish, Asterina pectinifera Muller and Troschel (Asterinidae) is an indigenous species commonly found in all coasts of Korea causes damages to shellfish farms. In order to exterminate A. pectinifera, they are dried and used as fertilizer. Although various studies have been conducted to create high added value from the retrieved A. pectinifera, their actual utilization is relatively low. Accordingly, this study aimed to find new practical uses of starfish by identifying useful ingredients for skin anti-aging. Two polyhydroxysteroids and one asterosaponin were isolated from the A. pectinifera. The structures of these compounds were identified as $5{\alpha}$-cholestane-$3{\beta},6{\alpha},7{\alpha},8,15{\alpha},16{\beta},26$-heptol, $5{\alpha}$-cholestane-$3{\beta},4{\beta},6{\alpha},7{\alpha},8,15{\beta},16{\beta},2$6-octol, and asterosaponin $P_1$ on the basis of chemical and spectroscopic analysis. Among these compounds, we have found that asterosaponin $P_1$ increased epidermal stem cell proliferation and the expression of hyaluronan synthase-2 and hyaluronan synthase-3 gene, which are enzymes that synthesize water-binding matrix hyaluronic acids in keratinocytes. In addition, asterosaponin $P_1$ increased synthesis of pro-collagen type I, a major dermal collagen in fibroblasts. As a result, asterosaponin $P_1$ isolated from A. pectinifera could be used as a useful cosmetic ingredient that improves skin symptoms accompanying skin aging.

키워드

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Figure 1. Isolation scheme of A. pectinifera.

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Figure 2. Chemical structure of compound 1, 2, and 3.

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Figure 3. Effect of compound 1, 2, and 3 on keratinocyte stem cells (KSCs) viability. After KSCs were treated with various concentrations of compound 1, 2, and 3 for 24 h, CCK-8 assay was performed. Data are shown as a percentage of control from three independent experiments in triplicate. *p < 0.05, ** p < 0.01 compared with the untreated control.

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Figure 4. Effect of compound 1, 2, and 3 on proliferation of keratinocyte stem cells (KSCs). Cells were incubated with various concentration of compound 1, 2, and 3 for 72 h. KSCs proliferation was measured using CCK-8 assay. Data are shown as a percentage of control from the three independent experiments in triplicate and values represent as the mean ± SD. *p < 0.05, ** p < 0.01 compared with the untreated control (BM, basal medium). Growth medium (GM) was used as a positive control.

HJPHBN_2018_v44n4_389_f0005.png 이미지

Figure 5. Transcriptional expression profile of HAS-2 and HAS-3 in compound 3-treated HaCaT cells. HaCaT cells were incubated with compound 3 for 24h. Total RNA was extracted and quantitative real time PCR was performed for HAS-2 (A) and HAS-3 (B). G3PDH was used as an internal control. Results are the mean ± SD. of experiments using data are shown as fold increase from the three independent experiments in triplicate. *p < 0.05, ** p < 0.01 compared with the untreated control. Retinoic acid (10-7 M) was used as a positive control.

HJPHBN_2018_v44n4_389_f0006.png 이미지

Figure 6. Collagen synthesis-promoting effects of compound 3. Collagen synthesis was evaluated using pro-collagen EIA assay. TGF-β (10 ng/mL) was used as a positive control. *p < 0.05, ** p < 0.01 compared with the untreated control.

참고문헌

  1. R. M. Lavker and T. T. Sun, Epidermal stem cells: properties, markers, and location, Proc. Natl. Acad. Sci. USA, 97(25), 13473 (2000). https://doi.org/10.1073/pnas.250380097
  2. L. Alonso and E. Fuchs, Stem cells of the skin epithelium, Proc. Natl. Acad. Sci. USA, 100(suppl.1), 11830 (2003). https://doi.org/10.1073/pnas.1734203100
  3. C. Blanpain and E. Fuchs, Epidermal stem cells of the skin, Annu. Rev. Cell. Dev. Biol., 22, 339 (2006). https://doi.org/10.1146/annurev.cellbio.22.010305.104357
  4. A. Webb, A. Li, and P. Kaur, Location and phenotype of human adult keratinocyte stem cells of the skin, Differentiation, 72(8), 387 (2004). https://doi.org/10.1111/j.1432-0436.2004.07208005.x
  5. J. R. Bickenbach, M. M. Stern, K. L. Grinnell, A. Manuel, and S. Chinnathambi, Epidermal stem cells have the potential to assist in healing damaged tissues, J. Investig. Dermatol. Symp. Proc., 11(1), 118 (2006). https://doi.org/10.1038/sj.jidsymp.5650009
  6. N. Gago, V. Perez-Lopez, J. P. Sanz-Jaka, P. Cormenzana, I. Eizaguirre, A. Bernad, and A. Izeta, Age-dependent depletion of human skin-derived progenitor cells, Stem Cells, 27(5), 1164 (2009). https://doi.org/10.1002/stem.27
  7. I. Ghersetich, T. Lotti, G. Campanile, C. Grappone, and G. Dini, Hyaluronic acid in cutaneous intrinsic aging, Int. J. Dermatol., 33, 119 (1994). https://doi.org/10.1111/j.1365-4362.1994.tb01540.x
  8. W. Manuskiatti and H. I. Maibach, Hyaluronic acid and skin: wound healing and aging, Int. J. Dermatol., 35, 539 (1996). https://doi.org/10.1111/j.1365-4362.1996.tb03650.x
  9. S. Karvinen, S. Pasonen-Seppanen, J. M. Hyttinen, J. P. Pienimaki, K. Toronen, T. A. Jokela, M. I. Tammi, and R. Tammi, Keratinocyte growth factor stimulates migration and hyaluronan synthesis in the epidermis by activation of keratinocyte hyaluronan synthase 2 and 3, J. Biol. Chem., 278(49), 49495 (2003). https://doi.org/10.1074/jbc.M310445200
  10. S. Kim, B. Y. Kang, S. Y. Cho, D. S. Sung, H. K. Chang, M. H. Yeom, D. H. Kim, Y. C. Sim, and Y. S. Lee, Compound K induces expression of hyaluronan synthase 2 gene in transformed human keratinocytes and increases hyaluronan in hairless mouse skin, Biochem. Biophys. Res. Comm., 316, 348 (2004). https://doi.org/10.1016/j.bbrc.2004.02.046
  11. T. Sayo, Y. Sugiyama, Y. Takahashi, N. Ozawa, S. Sakai, O. Ishikawa, M. Tamura, and S. Inoue, Hyaluronan synthase 3 regulates hyaluronan synthesis in cultured human keratinocytes, J. Invest Dermatol., 118, 43 (2002). https://doi.org/10.1046/j.0022-202x.2001.01613.x
  12. F. Liebel, S. Kaur, E. Ruvolo, N. Kollias, and M. D. Southall, Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes, J. Invest. Dermatol., 132(7), 1901 (2012). https://doi.org/10.1038/jid.2011.476
  13. L. Rittie and G. J. Fisher, UV-light-induced signal cascades and skin aging, Ageing Res. Rev., 1(4), 705 (2002). https://doi.org/10.1016/S1568-1637(02)00024-7
  14. Y. S. Kim, Selective feeding on the several bivalve molluscs by starfish, Asterias amurensis Lutken, Bull. Fac. Fish., 19, 244 (1969).
  15. K. H. Kang, J. M. Kim, and S. T. Oh, Predation of Asterias amurensis and Asterina pectinifera on valuable bivalves at different water temperature, Korean J. Malacol., 16(1-2), 17 (2000).
  16. Korean Patent 0044347 (2001).
  17. H. Y. Park, J. I. Lee, K. H. Nam, and M. S. Jang, Physiochemical characteristics of calcium supplement manufactured using starfish, Korean J. Food Preserv., 19(5), 727 (2012). https://doi.org/10.11002/kjfp.2012.19.5.727
  18. H. S. Jeong, M. C. Kwon, J. G. Han, J. H. Ha, L. Jin, J. C. Kim, H. G. Kwak, B. Y. Hwang, and H. Y. Lee, Enhancement of skin immune activation effect of collagen peptides isolated from Asterias amurensis. Korean J. Food Sci. Technol., 40(5), 522 (2008).
  19. M. C. Kwon, C. H. Kim, H. S. Kim, B. Y. Hwang, and H. Y. Lee, Anti-wrinkle activity of low molecular weight peptides derived from the collagen isolated from Asterias amurensis, Korean J. Food Sci. Technol., 39(6), 625 (2007).
  20. Korea Patent 10-2001-0030718 (2001).
  21. Korea Patent 10-2002-0004701 (2002).
  22. Korea Patent 10-2003-0090586 (2003).
  23. R. Higuchi, Y. Noguchi, T. Komori, and T. Sasaki, Biologically active glycosides from asteroidea, XVIII. $^{1}H-NMR$ spectroscopy and biological activities of polyhydroxylated steroids from the starfish Asterina pectinifera Muller et Troschel, Liebigs Ann. Chem., 1988(12), 1185 (1988). https://doi.org/10.1002/jlac.198819881214
  24. Z. Li, G. Chen, X. Lu, H. Wang, B. Feng, and Y. Pei, Three new steroid glycosides from the starfish Asterina pectinifera, Nat. Prod. Res., 27(20), 1816 (2013). https://doi.org/10.1080/14786419.2012.761621
  25. A. A. Kicha, A. I. Kalinovsky, E. V. Levina, V. A. Stonik, and G. B. Elyakov, Asterosaponin $P_{1}$ from the starfish Patiria pectinifera, Tetrahedron Lett., 24(36), 3893 (1983). https://doi.org/10.1016/S0040-4039(00)94305-3
  26. H. Zuo, T. Wang, Y. Qi, Q. Zhao, and Z. Li, Extraction, purification and cytotoxic activity of cerebrosides from Asterina pectinifera, Adv. Mater. Res., 781-784, 682 (2013). https://doi.org/10.4028/www.scientific.net/AMR.781-784.682
  27. Y. Peng, J. Zheng, R. Huang, Y. Wang, T. Xu, X. Zhou, Q. Liu, F. Zeng, H. Ju, X. Yang, and Y. Liu, Polyhydroxy steroids and saponins from China sea starfish Asterina pectinifera and their biological activities, Chem. Pharm. Bull., 58(6), 856 (2010). https://doi.org/10.1248/cpb.58.856
  28. N. P. Thao, N. X. Cuong, B. T. T. Luyen, N. V. Thanh, N. X. Nhiem, Y. S. Koh, B. M. Ly, N. H. Nam, P. V. Kiem, C. V. Minh, and Y. H. Kim, Anti-inflammatory asterosaponins from the starfish Astropecten monacanthus, J. Nat. Prod., 76(9), 1764 (2013). https://doi.org/10.1021/np400492a
  29. N. V. Ivanchina, A. A. Kicha, A. I. Kalinovsky, P. S. Dmitrenok, V. A. Stonik, R. Riguera, and C. Jimenez, Hemolytic polar steroidal constituents of the starfish Aphelasterias japonica, J. Nat. Prod., 63(8), 1178 (2000). https://doi.org/10.1021/np000030f
  30. W. Wang, F. Li, J. Hong, C. O. Lee, H. Y. Cho, K. S. Im, and J. H. Jung, Four new saponins from the starfish Certonardoa semiregularis, Chem. Pharm. Bull., 51(4), 435 (2003). https://doi.org/10.1248/cpb.51.435
  31. R. Riccio, A novel group of highly hydroxylated steroids from the starfish Protoreaster nodosus, Tetrahedron, 38(24), 3615 (1982). https://doi.org/10.1016/0040-4020(82)80069-0