DOI QR코드

DOI QR Code

Effect of Isoquercitrin-containing Nelumbo nucifera Leaves Extract on Skin Wrinkle Improvement

Isoquercitrin 함유 연꽃잎 추출물의 피부주름개선 효능 연구

  • Received : 2018.05.30
  • Accepted : 2018.06.25
  • Published : 2018.06.30

Abstract

In this study, we conducted research to find anti-wrinkle skin care ingredients from natural sources via the measurement of procollagen type 1 levels in the medium of normal human dermal fibroblast (NHDF) and found that a Nelumbo nucifera leave extract (NLE) was as the best effective ingredient. By the high performance liquid chromatography analysis, we confirmed isoquercitrin was one of the main compounds of NLE. Moreover, it also increased the procollagen type 1 production without cytotoxicity of NHDF. NLE and isoquercitrin exerted free radical scavenging activity. Especially, isoquercitrin exhibited strong intracellular antioxidant capacity in human skin-derived cells, HaCaT and NHDF. Finally, we performed clinical test for the inhibitory effect of NLE on skin wrinkle formation. A randomized study was conducted in 22 healthy female volunteers, aged between 30 and 65 yrs, with moderate to moderately severe facial wrinkles. Volunteer applied a 1.7% NLE cream (isoquercitrin 51 ppm) and a control cream at each facial side (left/right) twice daily for 8 weeks. The 1.7% NLE cream improved skin roughness through reducing the wrinkle of the craw's feet significantly without any skin side effect. Our results demonstrate that NLE and isoquercitrin can increase the collagen production and exert antioxidant activity. Therefore, we expect that the new non-toxic herbal extract, isoquercitrin-containing NLE will be interesting natural ingredient of cosmetics with anti-wrinkle efficacy.

본 연구에서는 제1형 프로콜라겐 분비량 측정을 통해 피부 주름개선 효과가 있는 천연물을 검색하던 중, 연꽃잎추출물(Nelumbo nucifera leaves extract, NLE)이 가장 우수한 효능을 나타냄을 확인하였다. 고압액체크로마토그래피로 NLE를 분석한 결과 isoquercitrin이 함유되어 있었으며, isoquercitrin도 normal human dermal fibroblast (NHDF)에서 제1형 프로콜라겐의 분비를 촉진한다는 것을 확인할 수 있었다. 또한 NLE와 isoquercitrin은 자유 라디컬 소거 활성을 가지고 있었으며, 특히 isoquercitrin은 인간 피부유래 세포주인 HaCaT 및 NHDF에서 활성산소종의 생성을 억제하고 총항산화능을 증가시켰다. 최종적으로 본 연구팀은 isoquercitrin의 함유량을 높이기 위해 정제한 NLE를 1.7% 함유한 크림(isoquercitrin 51 ppm 함유)을 제조하여 눈가의 주름개선 효과를 평가하였다. 30 ~ 65세의 한국인 여성 22명을 대상으로 얼굴의 한쪽 면엔 NLE 함유 크림을, 그리고 다른 한쪽 면엔 대조제품을 매일 2회씩, 8주간 연속 사용하도록 하였다. 그 결과 NLE 함유크림을 사용하였을 때 피부자극이 발견되지 않았으며, 대조제품과 비교하여 통계적 유의성 있게 눈가의 주름을 감소시키는 것을 확인할 수 있었다. 본 연구결과는 NLE 및 isoquercitrin이 우수한 콜라겐 생성 촉진 및 항산화 효능을 가지며, isoquercitrin 함유 NLE는 안전한 천연 주름개선 화장품 소재로 적용 가능하다는 것을 시사한다.

Keywords

References

  1. H. Masaki, Role of antioxidants in the skin: anti-aging effects, J. Dermatol. Sci., 58(2), 85 (2010). https://doi.org/10.1016/j.jdermsci.2010.03.003
  2. P. K. Mukherjee, D. Mukherjee, A. K. Maji, S. Rai, and M. Heinrich, The sacred lotus (Nelumbo nucifera) - phytochemical and therapeutic profile, J. Pharm. Pharmacol., 61(4), 407 (2009). https://doi.org/10.1211/jpp.61.04.0001
  3. R. Karki, M. A. Jung, K. J. Kim, and D. W. Kim, Inhibitory effect of Nelumbo nucifera (Gaertn.) on the development of atopic dermatitis-like skin lesions in NC/Nga mice, Evid. Based Complement. Alternat. Med., 153568, (2012).
  4. K. M. Park, Y. J. Yoo, S. Ryu, and S. H. Lee, Nelumbo Nucifera leaf protects against UVB-induced wrinkle formation and loss of subcutaneous fat through suppression of MCP3, IL-6 and IL-8 expression, J. Photochem. Photobiol. B., 161, 211 (2016). https://doi.org/10.1016/j.jphotobiol.2016.04.006
  5. D. H. Yoo, D. H. Joo, S. Y. Lee, and J. Y. Lee, Antioxidant effect of Nelumbo nucifera G. Leaf extract and inhibition of MITF, TRP-1, TRP-2, and tyrosinase expression in a B16F10 melanoma cell line, J. Life Sci., 25(10), 1115 (2015). https://doi.org/10.5352/JLS.2015.25.10.1115
  6. E. Middleton Jr, C. Kandaswami, and T. C. Theoharides, The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer, Pharmacol. Rev., 52(4), 673 (2000).
  7. C. G. Silva, R. J. Raulino, D. M. Cerqueira, S. C. Mannarino, M. D. Pereira, A. D. Panek, J. F. Silva, F. S. Menezes, and E. C. Eleutherio, In vitro and in vivo determination of antioxidant activity and mode of action of isoquercitrin and Hyptis fasciculata, Phytomedicine., 16(8), 761 (2009). https://doi.org/10.1016/j.phymed.2008.12.019
  8. A. Gasparotto Junior, F. M. Gasparotto, E. L. Lourenco, S. Crestani, M. E. Stefanello, M. J. Salvador, J. E. da Silva-Santos, M. C. Marques, and C. A. Kassuya, Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: evidence for the inhibition of angiotensin converting enzyme, J. Ethnopharmacol., 134(2), 363 (2011). https://doi.org/10.1016/j.jep.2010.12.026
  9. Y. Kim, S. Narayanan, and K. O. Chang, Inhibition of influenza virus replication by plant-derived isoquercetin, Antiviral Res., 88(2), 227 (2010). https://doi.org/10.1016/j.antiviral.2010.08.016
  10. A. P. Rogerio, A. Kanashiro, C. Fontanari, E. V. da Silva, Y. M. Lucisano-Valim, E. G. Soares, and L. H. Faccioli, Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma, Inflamm. Res., 56(10), 402 (2007). https://doi.org/10.1007/s00011-007-7005-6
  11. L. Li, X. H. Zhang, G. R. Liu, C. Liu, and Y. M. Dong, Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP kinases and NF-${\kappa}B$ in human KU812 cells, Chin. J. Nat. Med., 6, 407 (2016).
  12. C. M. Pennesi, J. Neely, A. G. Marks Jr, and S. A. Basak, Use of isoquercetin in the treatment of Prurigo nodularis, J. Drugs Dermatol., 16(11), 1156 (2017).
  13. K. Ohguchi, C. Nakajima, M. Oyama, M. Iinuma, T. Itoh, Y. Akao, Y. Nozawa, and M. Ito, Inhibitory effects of flavonoid glycosides isolated from the peel of Japanese persimmon (Diospyros kaki 'Fuyu') on melanin biosynthesis, Biol. Pharm. Bull., 33(1), 122 (2010). https://doi.org/10.1248/bpb.33.122
  14. N. Bhatia, G. Kaur, V. Soni, J. Kataria, and R. K. Dhawan, Evaluation of the wound healing potential of isoquercetin-based cream on scald burn injury in rats, Burns Trauma, 4, 7 (2016). https://doi.org/10.1186/s41038-016-0032-1
  15. Eui Kyun Park, So Ra Ahn, Dong-Hee Kim, Eun-Woo Lee, Hyun Ju Kwon, Byung Woo Kim, and Tae Hoon Kim, Effects of unripe apple polyphenols on the expression of matrix metalloproteinase-1 and type-1 procollagen in ultraviolet irradiated human skin fibroblasts, J. Korean Soc. Appl. Biol. Chem., 4(57), 449 (2014).
  16. T. Ihanamaki, L. J. Pelliniemi, and E. Vuorio, Collagens and collagen-related matrix components in the human and mouse eye, Prog. Retin. Eye Res., 23(4), 403 (2004). https://doi.org/10.1016/j.preteyeres.2004.04.002
  17. G. A. Di Lullo, S. M. Sweeney, J. Korkko, L. Ala-Kokko, and J. D. San Antonio, Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen, J. Biol. Chem., 277(6), 4223 (2002). https://doi.org/10.1074/jbc.M110709200
  18. J. J. Furth, The steady-state levels of type I collagen mRNA are reduced in senescent fibroblasts, J. Gerontol., 46(3), B122 (1991). https://doi.org/10.1093/geronj/46.3.B122
  19. G. J. Fisher, S. Kang, J. Varani, Z. Bata-Csorgo, Y. Wan, S. Datta, and J. J. Voorhees, Mechanisms of photoaging and chronological skin aging, Arch. Dermatol., 138(11), 1462 (2002).
  20. P. U. Giacomoni and G. Rein, Factors of skin ageing share common mechanisms, Biogerontology, 2(4), 219 (2001). https://doi.org/10.1023/A:1013222629919
  21. T. Stipcevic, J. Piljac, and D. Vanden Berghe, Effect of different flavonoids on collagen synthesis in human fibroblasts, Plant Foods Hum. Nutr., 61(1), 29 (2006).
  22. Y. Q. Li, F. C. Zhou, F. Gao, J. S. Bian, and F. Shan, Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase, J. Agric. Food Chem., 57(24), 11463 (2009). https://doi.org/10.1021/jf903083h
  23. J. M. Cruz-Zuniga, H. Soto-Valdez, E. Peralta, A. M. Mendoza-Wilson, M. R. Robles-Burgueno, R. Auras, and N. Gamez-Meza, Development of an antioxidant biomaterial by promoting the deglycosylation of rutin to isoquercetin and quercetin, Food Chem., 204, 420 (2016). https://doi.org/10.1016/j.foodchem.2016.02.130
  24. S. J. Kim, M. H. Lim, I. K. Chun, and Y. H. Won, Effects of flavonoids of Ginkgo biloba on proliferation of human skin fibroblast, Skin Pharmacol., 10(4), 200 (1997). https://doi.org/10.1159/000211505
  25. F. Verrecchia and A. Mauviel, TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene expression, Cell Signal., 16(8), 873 (2004). https://doi.org/10.1016/j.cellsig.2004.02.007
  26. N. Khansari, Y. Shakiba, and M. Mahmoudi, Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer, Recent Pat. Inflamm. Allergy Drug Discov., 3(1), 73 (2009). https://doi.org/10.2174/187221309787158371
  27. D. Harman, Aging: a theory based on free radical and radiation chemistry, J. Gerontol., 11(3), 298 (1956). https://doi.org/10.1093/geronj/11.3.298
  28. H. Tanaka, T. Okada, H. Konishi, and T. Tsuji, The effect of reactive oxygen species on the biosynthesis of collagen and glycosaminoglycans in cultured human dermal fibroblasts, Arch. Dermatol. Res., 285(6), 352 (1993). https://doi.org/10.1007/BF00371836
  29. S. Chae, M. J. Piao, K. A. Kang, R. Zhang, K. C. Kim, U. J. Youg, K. W. Nam, J. H. Lee, and J. W. Hyun, Inhibition of matrix metalloproteinase-1 induced by oxidative stress in human keratinocytes by mangiferin isolated from Anemarrhena asphodeloides, Biosci. Biotechnol. Biochem., 75(12), 2321 (2011). https://doi.org/10.1271/bbb.110465
  30. M. Z. Zhu, W. Wu, L. L. Jiao, P. F. Yang, and M. Q. Guo, Analysis of flavonoids in Lotus (Nelumbo nucifera) leaves and their antioxidant activity using macroporous resin chromatography coupled with LC-MS/MS and antioxidant biochemical assays, Molecules, 20(6), 10553 (2015). https://doi.org/10.3390/molecules200610553