Three Melanogenesis Inhibitors from the Roots of Veratrum nigrum

여로의 멜라닌 생성 억제 물질

  • 김호정 (엘지생활건강 화장품 연구소) ;
  • 강상진 (엘지생활건강 화장품 연구소) ;
  • 강세훈 (엘지생활건강 화장품 연구소) ;
  • 김철환 (전북대학교 생물과학부) ;
  • 정민환 (엘지화학 분석센타) ;
  • 진무현 (엘지생활건강 화장품 연구소)
  • Published : 2002.12.30

Abstract

Three melanogenesis inhibitors were isolated from the roots and rhizomes of Veratrum nigrum L. and were identified as (3S,20S,25S)-22,26-iminocholesta-5,22(N)-dien-3-ol (verazine), (3S,2OR,25S)-22,26-iminocholesta-5,22(N)-dien-3-ol (epi-verazine) and (3R,23R)-14,15,16,17- tetradehydroveratraman-3,23-diol (veratramine) on the basis of their spectroscopic data. It was turned out that these compounds did not directly inhibit tyrosinase activity, the key enzyme responsible for the formation of melanin pigment while these compounds showed strong inhibition on the melanogenesis in B16 F1 mouse melanoma $(IC_{50}<1\;{\mu}g/ml)$. Due to the strong inhibitory activity and safety compared to current whitening agents such as arbutin, kojic acid and AHA, the compound can be a good candidate for new skin whitening agents.

국내외의 각종 피부관련 약재를 중심으로 천연물 data-base를 구축하고, 이로부터 피부 미백에 효과가 있다고 언급된 한방 약재를 추출, 용매 분획하여 얻은 분획물들을 B16 melanoma cell assay를 이용하여 미백 효과를 평가하였다. 이들 중 특히 미백효과가 우수한 여로(藜蘆, Veratrum nigrum L.)의 뿌리를 대상으로 성분연구하여 3개의 미백유효성분인 (3S,20S,25S)-22,26-iminocholesta-5,22(N)-dien-3-ol (verazine), (3S,20R,25S)-22,26-iminocholesta-5,22(N)-dien-3-ol (epi-verazine) and (3R,23R)-14,15,16,17-tetradehydroveratraman-3,23,diol (veratramine)을 분리, 구조분석하였다. 여로로부터 분리된 3종의 미백 유효성분은 흑화 작용의 주요 효소인 tyrosinase에 대한 작용은 확인할수 없었으나, B16 F1 mouse melanoma에 대한 멜라닌 합성 억제능은 $IC_{50}<1\;{\mu}g/ml$로 강하게 나타났다. 또한 이와 같은 강한 멜라닌 합성 저해능을 갖는 이들 물질들의 안전성 확인을 통하여 향후 새로운 미백물질로 이용될 수 있을것으로 사료된다.

Keywords

References

  1. Komer A. and Pawelek J. (1980) Dopachrome conversion:a possible control point in melanin biosynthesis. J. Invest. Dermatol. 75: 192-195 https://doi.org/10.1159/000253515
  2. Chiang Su New Medical College. (1977) In Dictionary of Chinese Crude Drugs, Shanghai scientific technology publisher, 2692-2695. Shanghai
  3. Lo Komer A. and Pawelek J. (1980) Mammalian tyrosinase catalyzed three reactions in melanin tan, Cancer Res. 40: 3345-3350
  4. Gordon, P. R., Mansur, C. P. and Gilchrest, B. A. (1989) Regulation of human melanocyte growth, dendricity, and melanization by keratinocyte derived factors. J. Invest. Dermatol. 92: 566-572
  5. OECD GUIDELINE 429: Skin Sensitisation: Local Lymph Node Assay (2001)
  6. Maged S. Abdel-Kader, Braian D. Bahler, Stan Malone, Marge C. M. Werkhoven, Frits van Troon, David, Jan H. Wisse, Isia Bursuker, Kim M. Neddennann, Stephen W. Mamber, and David G. I. Kingston. (1998) DNA-Damaging steroidal alkaloids from Eclipta alba from the suriname rainforest. J. Nat. Prod. 61: 1202-1208 https://doi.org/10.1021/np970561c
  7. Yasuhiro Tezuka, Tohru Kikuchi, Weijie Zhao, Jun Chen, and Yongtian Guo. (1998) (+)-Verussurine, a new steroidal alkaloid from the roots and rhizomes of Veratrum nigrum var. ussuriense and structure revision of (+)-verabenzoamine. J. Nat. Product. 61: 1397-1399 https://doi.org/10.1021/np9800811
  8. Weijie Zhao, Yasuhiro Tezuka, Tohru Kikuchi, Jun Chen, and Yongtian Guo. (1991) Studies on the constituents of Veratrum plants, II. Constituents of Veratrum nigrum L. var ussuriense. (1). Structure and $\1^{H}$- and $\^13{C}$-nuclear magnetic resonance spectra of a new alkaloid, Verussurinine, and related alkaloids. Chem. Pharm. Bull. 39: 549-554 https://doi.org/10.1248/cpb.39.549
  9. Yasuhiro Tezuka, Tohru Kikuchi, Weijie Zhao, Jun Chen, and Yongtian Guo. (1998) Two new steroidal alkaloids, 20-isoveratramine and verapatuline, from the roots and rhizomes of Veratrum patulum. J. Nat. Prot. 61: 1078-1081 https://doi.org/10.1021/np980150b
  10. Browne, C. A., Sim, F. R., Rae, I. D. and Keeler, R. F. (1984) Isolation of teratogenic alkaloids by reversed phase high performance liquid chromatography. J. Chromatography. 336: 211-220 https://doi.org/10.1016/S0378-4347(00)85143-9