3,9-Diferuloyl-6-oxopterocarpen (Tensolin-F$^\circledR$): a Novel Anti-wrinkle Agent for Cosmeceuticals

새로운 주름개선 소재: 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^\circledR$)의 개발과 화장품 응용

  • 이범천 (한불화장품(주) 기술연구소) ;
  • 이정재 (한불화장품(주) 기술연구) ;
  • 박성민 (한불화장품(주) 기술연구) ;
  • 김철배 (한불화장품(주) 기술연구) ;
  • 심관섭 (한불화장품(주) 기술연구) ;
  • 김진화 (한불화장품(주) 기술연구) ;
  • 이근수 (한불화장품(주) 기술연구) ;
  • 이천일 (한불화장품(주) 기술연구) ;
  • 표형배 (한불화장품(주) 기술연구소)
  • Published : 2004.05.01

Abstract

As a novel anti-wrinkle agent, 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^{(R)}$) has been synthesized and its anti-aging effects have been investigated. In the present study, to investigate the relationship between aging and Tensolin-F$^{(R)}$, we examined its effect on scavenging activities of radicals and reactive oxygen species (ROS), in vitro inhibition activity of matrix-metalloproteinase (MMP) and expression of UVA-induced MMPs in human dermal fibroblasts (HDF). Tensolin-F$^{(R)}$ was found to show activities of scavenging radicals and ROS with the $IC_{50}$/ values of 0.2 mM and 0.95 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide radicals, respectively, in the xanthine/xanthine oxidase system. Fluorometric assays for the proteolytic activities of MMP-l (collagenase) were performed using fluorescent collagen substrates. Tensolin-F$^{(R)}$ inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 0.025 mM. Also, UVA induced MMP-1 expression was reduced 85% by treatment with Tensolin-F$^{(R)}$ at 0.8 uM, which was reduced dose-dependent manner. The results of clinical study showed that 4.8 mM Tensolin-F$^{(R)}$ treated group reduced wrinkle significantly compared with placebo treated group (P 〈 0.05). Taken together, these result suggest that Tensolin-F$^{(R)}$ act as an anti-wrinkle agent by taking effects to antioxidation and reducing UVA-induced MMP-l production.-l production.

3,9-Dihydro-6-oxopterocarpen과 ferulic acid의 에스테르 반응을 통해 페룰산 유도체인 3,9-diferuloyl-6-oxopterocarpen (Tensolin-$F_{(R)}$ )를 합성하여 이를 함유한 주름개선 화장품을 개발하였다. Tensolin-$F_{(R)}$ 는 농도 의존적으로 DPPH와 superoxide radical에 대한 소거효과를 나타냈으며, 각각 0.8 mM에서 78%, 0.053 mM에서 92.9%로 DPPH와 superoxide radical을 소거하여 우수한 항산화 효과를 나타내었다. MMP-1 효소 활성 저해 효과도 0.16 mM에서 74%를 저해하였다. HDF에서 UVA에 의해 발현이 증가되는 MMP-1의 발현 저해 효과는 Tensolin-$F_{(R)}$ 0.8 uM에서 85.5%로 단백질 수준에서 모두 농도 의존적으로 발현 저해효과가 나타났다. Tensolin-$F_{(R)}$ 를 함유한 제품의 피부 주름개선 효과 평가 결과, Tensolin-$F_{(R)}$ 를 함유한 화장품을 약 8주 간 도포한 경우 유의한 주름개선 효과가 있음을 확인 할 수 있었다. 본 연구를 통하여 Tensolin-$F_{(R)}$ 는 항산화 효과와 MMP-1활성 저해 효과 및 UVA에 의한 MMP-1의 발현을 저해하는 효과가 나타났으며 새로운 주름개선 기능성 화장품으로 이용될 수 있을 것이다.

Keywords

References

  1. Free radical Biol & Med. v.26 Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line S.Claude;K.Manabu;M.Laura;P.Lester https://doi.org/10.1016/S0891-5849(98)00212-3
  2. Ann. Rev. Biochem v.55 Reactive oxygen intermediate in biochemistry A.Naqui;B.Chance;E.Cadenas https://doi.org/10.1146/annurev.bi.55.070186.001033
  3. Ann. Rev. Biochem v.58 Biochemistry of oxygen toxicity E.Cadenas https://doi.org/10.1146/annurev.bi.58.070189.000455
  4. J. Biol. Chem. v.262 Protein damage and degradation by oxygen radicals K.J.Davies
  5. J. Soc. Cos. Sci. Kor. v.23 Skin aging and antioxidant S.N.Park
  6. J. Investing. Dermatol. Symp. Proc. v.3 Aging versus photoaging: postulated mechanisms and effectors M.Yaar;B.A.Gilchrest
  7. Cancer Research v.56 Inhibition of tumor promoter-induced transformation by reinoids that transrepress AP-1 without transactivating retinoic acid response element J.J.Li;Z.Dong;M.I.Dawson;N.H.Colburn
  8. J. Invest. Dermatol. v.94 Retinoic acid inhibits the production of collagenase by human epidermal keratinoytes C.Bailly;S.Dreze;D.Asselineau;B.Nusgens;C.M.Lapiere;M.Darmon https://doi.org/10.1111/1523-1747.ep12873342
  9. Proc. Natl. Acad. Sci. v.94 Blocking activator proteinl activity, but not activation retinoic acid response element, is required for the antitumor promotion effect of retinoic acid C.Huang;W.Y.Ma;M.I.Dawson;M.Rincon;R.A.Flavell;Z.Dong https://doi.org/10.1073/pnas.94.11.5826
  10. J. Clin Invest. v.101 Retinoic acid inhibits induction of c-Jun protein by Ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo G.J.Fisher;S.W.Kang;J.J.Voorhees https://doi.org/10.1172/JCI2153
  11. Photochem. Photobiol. v.69 Molecular mechanisms of photoaging in human skin in vivo and their provention by all-rans retinoic acid G.J.Fisher;J.J.Voorhees https://doi.org/10.1111/j.1751-1097.1999.tb03268.x
  12. J. Dermatol. Sci. v.17 All-trans-retinoic acid down-regulates elastin promoter activity elevated by ultraviolet B irradiation in cultured skin fibroblasts K.S.Lee;S.J.Kim;Y.W.Ryoo;B.C.Kim https://doi.org/10.1016/S0923-1811(98)00004-8
  13. Pigment Cell Res. v.13 Depigmentation effect of α-tocopheryl ferulate on normal human melanocytes F.Yoko;K.Mari;I.Masamitsu https://doi.org/10.1111/j.0893-5785.2000.130830.x
  14. Syn. Comm. v.12 A.Arrieta;T.Garcia;C.Palomo https://doi.org/10.1080/00397918208065981
  15. JACS v.80 O.H.Emerson;E.M.Bickoff https://doi.org/10.1021/ja01549a067
  16. Nature v.181 Antioxidant determinations by the use of a stable free radical M.S.Blois https://doi.org/10.1038/1811199a0
  17. Biol. Pharm. Bull. v.25 The ontribution of the pyrogallol moiety to the suproxide radical savenging activity of flavonoids K.Furuno;T.Akasako;N.Sugihara https://doi.org/10.1248/bpb.25.19
  18. J. Immun. Methods v.65 Rapid colorimetric assay for the celluar growth and survival : application ro proliferation and cytotoxic assay T.Mosmann https://doi.org/10.1016/0022-1759(83)90303-4
  19. Chen. Pharm. Bull. v.40 A remarkable antoxidation effect of natural phenol derivatives on the autoxidation of γ-irradiated methyl linolate A.Kitahara;U.Matsumoto;H.Ueda;R.Ueoka https://doi.org/10.1248/cpb.40.2208
  20. Natural Medicines v.49 Constituents of natural medicines with scavenging effects on active oxygen species-Tannins and related polyphenols T.Hatano
  21. Biol. Pharm. Bull. v.18 Active oxygen scavenging activity of plant extracts H.Masaki;S.Sakaki;T.Atsumi;H.Sakurai https://doi.org/10.1248/bpb.18.162
  22. J. Biol. Chem. v.264 Characterization of free radical generation by xanthine oxidase P.Kuppusamy;J.L.Zweier
  23. J. Invest. Dermatol. v.115 Decreased extraellularsignal regulated kinase and increased stress-activated MAP kinaase activities in aged human skin in vivo J.H.Chun;S.W.Kang;J.Varani;J.Lin;G.J.Fisher;J.J.Voorhees https://doi.org/10.1046/j.1523-1747.2000.00009.x
  24. J. Clin. Invest. v.101 Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo G.J.Fisher;H.S.Talwar;J.Lin;P.Lin;P.McPhillips;Z.Q.Wang;X.Li;Y.Wan;S.W.Kang;J.J.Voorhees https://doi.org/10.1172/JCI2153
  25. Kor. J. Invest. Dermatol. v.8 The effect of ultraviolet irradiation on the expression of typeⅠprocollagen and MMP-1 in human dermal fibroblast and human skin in vivo J.Y.Seo;G.E.Rhie;J.H.Chung
  26. Kor. J. Invest. Dermatol. v.8 The effect of retionic acid and vitamin C on the expression of the proollagen α-1(Ⅰ), tropoelastin, and MMP-1 in human dermal fibroblast J.Y.Seo;H.R.Choi;G.E.Rhie;C.S.Youn;W.W.Choi;J.A.Kim;J.H.Chung;K.H.Kim;K.H.Cho;H.C.Eun
  27. FEBA Lett. v.331 Singlet oxygen induces collagenase expression in human skin fibroblast S.K.Kohanek;M.Wlaschek;K.Briviba;H.Sies https://doi.org/10.1016/0014-5793(93)80357-Z
  28. J. Invest. Dermatol. v.104 Singlet oxygen may mediate the ultraviolet A induced syntyesis of interstitial collagenase M.Wlaschek;K.Brviba;G.P.Stricklin;H.Sies;S.K.Kochanek https://doi.org/10.1111/1523-1747.ep12612751