DOI QR코드

DOI QR Code

Icariin의 멜라닌합성 촉진 작용

Icariin promotes melanin synthesis

  • 차수빈 (원광대학교 한의학전문대학원 한약자원개발학과) ;
  • 박설아 (원광대학교 대학원 뷰티디자인학과) ;
  • 강리아민주 (원광대학교 한의학전문대학원 한약자원개발학과) ;
  • 우원홍 (원광대학교 한의과대학 해부학교실) ;
  • 문연자 (원광대학교 한의학전문대학원 한약자원개발학과)
  • Cha, Su Bin (Department of Herbal Resources, Professional Graduate School of Korean Medicine, Wonkwang University) ;
  • Park, Seol A (Department of Beauty Design Graduate School, Wonkwang University) ;
  • Kang, Lea Minju (Department of Herbal Resources, Professional Graduate School of Korean Medicine, Wonkwang University) ;
  • Woo, Won Hong (Deptartment of Anatomy, College of Korean Medicine, Wonkwang University) ;
  • Mun, Yeun Ja (Department of Herbal Resources, Professional Graduate School of Korean Medicine, Wonkwang University)
  • 투고 : 2020.02.12
  • 심사 : 2020.02.26
  • 발행 : 2020.02.28

초록

Objectives : This study was conducted to investigate the effects of major constituents of Epimedium koreanum Nakai (Icariin, epimedium A, epimedium B, and epimedium C) on melanin synthesis. Methods : We measured melanin contents, tyrosinase activity, and expression of Rab27a in B16F10 cells cultured with Epimedium koreanum Nakai ethanol extract (EKN) and their major constituents. After treatment with H89 and dibutyryl cAMP, which inhibit or promote the activation of PKA, we observed changes in melanin synthesis and tyrosinase activity stimulated by EKN. Results : Among them, EKN and icariin enhanced tyrosinase activity and melanin contents. We confirmed that EKN augmented melanin synthesis via cAMP/PKA pathway. Icariin-induced tyrosinase activity and melanin content were attenuated by PKA inhibitor H89, while melanogenic effect of icariin was further augmented by cAMP analog, dbc AMP. However, icariin did not affect the expression of small GTPase Rab27a involved in melanosome transport. Conclusions : These results suggest that icariin promotes melanogenesis through cAMP/PKA pathway but does not affect small GTPase Rab27a.

키워드

참고문헌

  1. Ma H, He X, Yang Y, Li M, Hao D, Jia Z. The genus Epimedium: An ethnopharmacological and phytochemical review. J Ethnopharm. 2011;134:519-41. https://doi.org/10.1016/j.jep.2011.01.001
  2. Zhao HY, Sun JH, Fan MX, Fan L, Zhou L, Li Z, Han J, Wang BR, Guo DA. Analysis of phenolic compounds in Epimedium plants using liquid chromatography coupled with electrosprey ionization mass spectrometry. J Chromatogr A. 2018;1190:157-81. https://doi.org/10.1016/j.chroma.2008.02.109
  3. Shin KH, Lim SS, Ahn SD, Kim SK, Park KY. Difference in components of Epimedium koreanum in compliance with seasons and places of collection. Kor J Medicinal Crop Sci. 1996;4:321-8.
  4. Kim DH, Jung HA, Sohn HS, Kim JW, Choi JS. Potential of Icariin Metabolites from Epimedium koreanum Nakai as Antidiabetic Therapeutic Agents. Molecules. 2017;22(6):E986, doi:10.3390/molecules22060986.
  5. Han YH, Choi BR, Soh HS, Lee SJ, Choi YJ, Kim SY. In vitro plant regeneration for mass propagation of Epimedium koreanum Nakai. Kor J Hort Sci Technol. 2000;18:834.
  6. Cho WK, Kim H, Choi YJ, Yim NH, Yang HJ, Ma JY. Epimedium koreanum Nakai water extract exhibits antiviral activity against porcine epidermic diarrhea virus in vitro and in vivo. Evid. Based Complement. Alternat Med. 2012;2012:985151
  7. Hang DH, Yang J, Lu XM, Deng Y, Xiong ZL, Li FM. An integrated plasma and urinary metabonomic study using UHPLC-MS: intervention effects of Epimedium koreanum on ‘kidney-Yang Deficiency syndrome' rats. J Pharm Biomed. 2013;76:200-6. https://doi.org/10.1016/j.jpba.2012.12.022
  8. Xu FF, Ding Y, Guo YY, Liu BY, Kou ZN, Xiao W, et al. Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-levle approach. J Ethnopharmacol. 2016;177:148-60. https://doi.org/10.1016/j.jep.2015.11.007
  9. Fan YP, Ren MM, Hou WF, Guo C, Tong DW, Ma L, et al. The activation of Epimedium koreanum Nakai polysaccharide- propolis flavones liposome on Kupffer cells. Carbohyd Polym 2015;133:613-23. https://doi.org/10.1016/j.carbpol.2015.07.044
  10. Inokuchi J, Okabe H, Yamauch T, Nagamatsu A. Inhibitors of angiotensin-converting enzyme in crude drugs. J Chem Pharm Bull. 1984;32:3615-9. https://doi.org/10.1248/cpb.32.3615
  11. Zhang HY, Li YJ, Yang XD, Wnag K, Ni JZ, Qu XG. Inhibitory effect of Epimedium extract on S-adenosyl-L-homocystein hydrolase and biomethylation. Life Sci. 2005;78:180-6. https://doi.org/10.1016/j.lfs.2005.04.057
  12. Keum JH, Han HY, Roh HS, Seok JH, Lee JK, Jeong J, Kim JA, Woo MH, Choi JS, Min BS. Analysis and stability test of the extracts from Epimedii Herba, Atractylodis Rhizoma Alba and Polygalae Radix for toxicity study. Korean J Pharmacogn. 2014;45: 135-40.
  13. Li WK, Xiao PG, Pan JQ. Complete assignment of 1H- and 13C-NMR spectra of ikarisoside A and epimedoside C. Magn Reson Chem. 1998;36:303-4. https://doi.org/10.1002/(SICI)1097-458X(199804)36:4<303::AID-OMR187>3.0.CO;2-I
  14. Li WK, Pan JQ, Lu MJ, Zhang RY, Xiao PG. A 9,10-dihydrophenanthrene derivate from Epimedium koreanum. Phytochemistry. 1995;39:231-3. https://doi.org/10.1016/0031-9422(94)00926-K
  15. Wang SP, Shen P, Lee L, Li Y, Yong EL. Pharmacokinetics of prenylflavonoids and correlations with the dynamics of estrogen action in sera following ingestion of a standardized Epimedium extract. J Pharm Biomed Anal. 2009;50:216-23. https://doi.org/10.1016/j.jpba.2009.04.022
  16. Zhao Y, Chen S, Wang Y, Lu C, Wang J, Lu J. Effect of drying processes on prenylflavonoid content and antioxidant activity of Epimedium koreanum Nakai. J Food & Drug Analysis. 2018;26:796-806. https://doi.org/10.1016/j.jfda.2017.05.011
  17. Indran IR, Liang ZRL, Min TE, Yong EL. Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health. Pharmacol Ther. 2016;162:188-206. https://doi.org/10.1016/j.pharmthera.2016.01.015
  18. Gong MJ, Han B, Wang SM, Liang SW, Zou ZJ. Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats. J Pharm Biomed Anal. 2016;123:63-73. https://doi.org/10.1016/j.jpba.2016.02.001
  19. Guo YM, Zang XT, Meng J, Wang ZY. An anticancer agent icariin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells. Eur J Pharmacol. 2011;658:114-22. https://doi.org/10.1016/j.ejphar.2011.02.005
  20. Mok SK, Chen WF, Lai WP, Leung PC, Wang XL, Yao XS, et al. Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor- dependent osteoblastic functions in UMR 106 cells. Br J Pharmacol. 2010;159:939-49. https://doi.org/10.1111/j.1476-5381.2009.00593.x
  21. Zhang Y, Shen L, Mao Z, Wang N, Wang X, Huang X, Shou D, Wen C. Icariin Enhances Bone Repair in Rabbits with Bone Infection during Post-infection Treatment and Prevents Inhibition of Osteoblasts by Vancomycin. Front Pharmacol. 2017;8:784, doi: 10.3389/fphar.2017.00784.
  22. Chung BH, Kim JD, Kim CK, Kim JH, Won MH, Lee HS, Dong MS, Ha KS, Kwon YG, Kim YM. Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells. Biochem Biophys Res Commun. 2008;376(2):404-8. https://doi.org/10.1016/j.bbrc.2008.09.001
  23. Lee EJ, Bae SY, Lee YH. The Stimulatory Effects of Epimedium koreanum Nakai Extract on Melanogenesis. J Soc Cosmet Scientists Korea. 2009;35:265-70.
  24. Ko JA, Park EY, Kim SN, Kim YC. The Effect of Epimedium koreanum Water Extracton the Enzymes and Factor Relevant to Melanin Synthesis in Vitro Test. J Investigative Cosmetology. 2011;7:45-52. https://doi.org/10.15810/jic.2011.7.1.007
  25. Cha SB, Kim DH, Mun YJ, Woo WH. Melanogenic Effect and the Mechanism of Epimedium koreanum Nakai. J Physiol & Pathol Korean Med. 2017;31(4):226-32. https://doi.org/10.15188/kjopp.2017.08.31.4.226
  26. Martinez-Esparza M, Jimenez-Cervantes C, Solano F, Lozano JA, Garcia-Borron JC. Mechanisms of melanogenesis inhibition by tumor necrosis factor-alpha in B16/F10 mouse melanoma cells. Eur J Biochem. 1998;255:139-46. https://doi.org/10.1046/j.1432-1327.1998.2550139.x
  27. Hosoi JE, Suda T, Kuroki T. Regulation of melanin synthesis of B16 mouse melanoma cells by 1a, 25-dehydroxyvitamin D3 and retinoic acid. Cancer Res. 1985;45:1474-8.
  28. Chen XJ, Ji H, Zhang QW, Tu PF, Wang YT, Guo BL, Li SP. A rapid method for simultaneous determinatin of 15 flavonoids in Epimedium using pressurized liquid extraction and ultra-performance liquid chromatography. J Pharm Biomed Anal. 2008;46:226-35. https://doi.org/10.1016/j.jpba.2007.09.016
  29. Islam NM, Yoo HH, Lee MW, Dong MS, Park YI, Jeong HS, Kim DH. Simultaneous quantitation of five flavonoid glycosides in Herba Epimedii by high-performance liquid chromatography-tandem mass spectrometry. Phytochem Anal. 2008;19:71-7. https://doi.org/10.1002/pca.1018
  30. Hume AN, Seabra MC. Melanosomes on the move: a model to understand organelle dynamics. Biochem Soc Trans. 2011;39:1191-6. https://doi.org/10.1042/BST0391191
  31. Kim B, Lee JY, Lee HY, Nam KY, Park J, Lee SM, Kim EJ, Lee JD, Hwang JS. Hesperidin supresses melanosome transport by blocking the interaction of Rab27A-melanophilin. Biomol Ther. 2013;21:343-8. https://doi.org/10.4062/biomolther.2013.032
  32. Robinson CL, Evans RD, Sivarasr K, Ramalho JS, Briggs DA, Hume AN. The adaptor protein melanophilin regulatea dynamic myosin-Va:cargo interaction and dendrite development in melanocytes. Molecular Biol Cell. 2019;30:742-52. https://doi.org/10.1091/mbc.E18-04-0237