研究生: |
劉思秀 |
---|---|
論文名稱: |
Chlorogenic acid及Hydroxybenzyl Alcohols之美白功效及機制探討及模擬皮膚系統之建立 Effects of Chlorogenic Acid and Hydroxybenzyl Alcohols on Melanogenesis in Co-culture and Skin Equivalents Composed of Murine Keratinocytes and Melanocytes |
指導教授: | 朱一民 |
口試委員: | |
學位類別: |
博士 Doctor |
系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
論文出版年: | 2007 |
畢業學年度: | 96 |
語文別: | 中文 |
中文關鍵詞: | 黑色素 、酪胺酸酶 、黑色素細胞 、角質細胞 、纖維母細胞 、共同培養 、模擬皮膚 、老鼠實驗 |
相關次數: | 點閱:1 下載:0 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
黑色素的含量及分佈狀況是決定皮膚及頭髮顏色的主要原因,由於酪胺酸酶是黑色素形成的主要關鍵酵素,所以利用抑制酪胺酸酶活性去阻止黑色素過度形成是目前最安全有效的美白方式。本實驗是使用chlorogenic acid和hydrobenzyl alcohols測試抑制酵素活性的作用,分別利用不同美白測試系統,探討活性成分對於黑色素生成及細胞生理機制的關係。結果顯示0.8 mM chlorogenic acid會使黑色素細胞中的黑色素含量降低56%,而4-hydrobenzyl alcohol濃度達1.0 mM時黑色素含量降低至45%,而且沒有觀察到細胞毒殺性的情形。此外由於在哺乳動物皮膚中黑色素的生成會受到角質細胞、纖維母細胞及其他調控因子的影響,因此我們利用黑色素細胞及角質細胞建立共同培養的系統作為皮膚模擬模式,來研究黑色素抑制及刺激因子在此系統中對於黑色素調控的影響。由實驗結果證實1.0 mM 4-hydrobenzyl alcohol在黑色素細胞及角質細胞建立的系統中黑色素含量降低33%,而且不會影響與黑色素形成相關的基因。在老鼠實驗中可以明確觀察到hydrobenzyl alcohols的美白功效性及安全性,而且在模擬皮膚的系統上也可以看到相同的結果。所以hydrobenzyl alcohols在美白保養品上的使用上有廣泛的應用價值,值得更深入研究及探討。我們也希望藉由模擬皮膚的系統能夠取代傳統動物實驗的方法。
﹝1﹞ Jimbow K, Quevedo WC, Prota G. Biology of melanocytes. In: Freedberg IM, Eisen AZ, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine, 5th ed. New York: McGraw-Hill; 1999.
﹝2﹞ Jimbow K. Current update and trends in melanin pigmentation and melanin biology. Keio J Med 1995; 44: 9–18.
﹝3﹞ Hsu M, Andl T, Li G, Meinkoth JL, Herlyn M. Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression. J Cell Sci 2000; 113: 1535–1542.
﹝4﹞ Herlyn M, Shih IM. Interactions of melanocytes and melanoma cells with the microenvironment. Pigment Cell Res 1994; 7: 81–88.
﹝5﹞ Kippenberger S, Bernd A, Bereiter-Hahn J, Ramirez-Bosca A, Kaufmann R. The mechanism of melanocyte dendrite formation: the impact of differentiating keratinocytes. Pigment Cell Res 1994; 11:34–37.
﹝6﹞ Jouneau A, Yu YQ, Pasdar M., Larue L. Plasticity of cadherin-catenin expression in the melanocyte lineage. Pigment Cell Res 2000; 13: 260–272.
﹝7﹞ Gordon, PR, Mansur, CP, Gilchrest, BA: Regulation of human melanocyte growth, dendricity and melanization by keratinocyte derived factors. J Invest Dermatol 1989; 92: 565–572.
﹝8﹞ Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y. The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis. Pigment Cell Res 1997; 10: 218–228.
﹝9﹞ Virador VM, Muller J, Wu X, Abdel-Malek ZA, Yu ZX, Ferrans VJ, Kobayashi N, Wakamatsu K, Ito S, Hammer JA, Hearing VJ. Influence of alpha-melanocyte-stimulating hormone and ultraviolet radiation on the transfer of melanosomes to keratinocytes. FASEB J 2002; 16: 105–107.
﹝10﹞ Kippenberger S, Bernd A, Bereiter-Hahn J, Ramirez-Bosca A, Kaufmann R, Holzmann H. Transcription of melanogenesis enzymes in melanocytes: dependence upon culture conditions and co-cultivation with keratinocytes. Pigment Cell Res 1996; 9:179–184.
﹝11﹞ Pawelek JN, Korner AM. The biosynthesis of mammalian melanin. Am Sci 1982; 70: 136–145.
﹝12﹞ Seo SY, Sharma VK, Sharma N. Mushroom tyrosinase. J Agric Food chem. 2003; 51:2837- 2853.
﹝13﹞ Imokawa G, Miyagishi M, Yada Y. Endothelin-1 as a new melanogen: Coordinated expression of its gene and thet tyrsinase gene in UVB-exposed human epidermis. J Invest Dermatol 1995; 105:32 -37.
﹝14﹞ Prota G. Progress in the chemistry of melanias and related metabolites. Med Res Rev 1988; 8: 525–556.
﹝15﹞ Virador VM, Muller J, Wu X, Abdel-Malek ZA, Yu ZX, Ferrans VJ, Kobayashi N, Wakamatsu K, Ito S, Hammer JA, Hearing VJ. Influence of alpha-melanocyte-stimulating hormone and ultraviolet radiation on the transfer of melanosomes to keratinocytes. FASEB J 2002; 16: 105–107.
﹝16﹞ Pawelek JM, Korner AM. The biosynthesis of mammalian melanin. Am Sci 1982; 70:136–145.
﹝17﹞ Hepp AF, Himmelwright RS, Eickman NC, Solomon EI. Ligand displacement reactions of oxyhemocyanin : comparison of reactivities of arthropods and mollusks. Biochem Riophys 1979; 89: 1050-1057.
﹝18﹞ Himmelwright RS, Eickman NC, LuBien CD, Solomon EI. Chemical and spectroscopic comparison of the binuclear copper active site of mollusc and arthropod hemocyanins. J Am Chem Soc 1980; 102: 5378-5388.
﹝19﹞ Lerch K. Tyrosinase and dopamine P-monooxygenase. In Metal Ions in Biological Systems. Marcel Dekker, New York, 1981; 143-186.
﹝20﹞ Sanchez FA, Rodriguez JN, Garcia CF, Carcia CF. A comprehensive review of its mechanism. Biochem Biophys Acta 1995; 1247, 1-11.
﹝21﹞ Jimbow K, Quevedo WC, Prota G. Biology of melanocytes. In: Freedberg IM, Eisen AZ, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine, 5th ed. New York: McGraw-Hill; 1999.
﹝22﹞ Giuseppe P. Melanins and Melongenesis. Cosmetics and Toiletries 1996; 111: 43–51.
﹝23﹞ Kim YJ, Uyama H. Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 2005; 62: 1707–1723.
﹝24﹞ Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003; 16: 101-110.
﹝25﹞ Andrawis A, Khn V. Effect of methimazole on the activity of mushroom tyrosinase. Biochem J 1986; 235, 91-96.
﹝26﹞ Obika M, Negishi S. Melanosome of toad: a storehouse of Riboflavin. Exp Cell Res 1972; 70,293-300.
﹝27﹞ Shimizu K, Kondo R, Sakai K. Inhibition of tyrosinase by flavonoids, stilbenes and related-4-substituted resorcinols:. structure-activity investigations. Planta Med 2000; 66, 11-15.
﹝28﹞ Tur W. Increasing the effectiveness. Cosmetics and Toiletries 1990;105:79-85.
﹝29﹞ Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R. Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol 1998; 142: 827–835.
﹝30﹞ Goding CR. Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev 2000; 14: 1712 –1728.
﹝31﹞ Nordlund JJ, Boissy RE, Hearing VJ, King RA, Ortonne JP. The physical properties of melanins. In The Pigmentary System. Oxford University Press 1998.
﹝32﹞ Nicholas JL, Nadim AS, Madhu AP. Sunscreens: development, evaluation, and regulatory aspects. 1997.
﹝33﹞ Kim YJ, Uyama H. Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 2005; 62: 1707–1723.
﹝34﹞ Funayama M, Arakawa H, Yamamoto R, Nishino, Shin T, Murao S. Effects of a- and b-arbutin on activity of tyrosinases from mushroom and mouse melanoma. Biosci Biotechnol Biochem 1995; 59:143–144.
﹝35﹞ Whitaker JR. Polyphenoloxidase. In: Wong D.W.S, editor. Food Enzymes. Structure and Mechanism. New York: Chapman & Hall; 1995.
﹝36﹞ Michaelis L, Menten M. Die Kinetik der Invertinwirkung, Biochem. Z.1913; 49:333-369.
﹝37﹞ Briggs GE, Haldane JBS, A note on the kinetics of enzyme action, Biochem. J.1925; 339-339.
﹝38﹞ Chen Y, Wu JW, Xu GJ, Tsou CL, Wang ZX. Chemotaxis in a lymphocyte cell line transfected with C-C chemokine receptor 2B: evidence that directed migration is mediated by betagamma dimers released by activation of Galphai-coupled receptors.Proc Natl Acad Sci U S A. 1997; 94:14495-14499.
﹝39﹞ Chen Y, Wu JW, Xu GJ, Tsou CL, Wang ZX. Inactivation kinetics of the reduced spinach chloroplast fructose-1,6-bisphosphatase by subtilisin. Eur J Biochem. 1997; 248(3):925-929.
﹝40﹞ Xue GJ, Tsou CL. kineticsi of the effect of inhibitors on systems involving two enzyme-substrate intermediates. Sci Sin. 1964; 13:269-277.
﹝41﹞ Liu W, Tsou CL. Determination of rate constants for the irreversible inhibition of acetylcholine esterase by continuously monitoring the substrate reaction in the presence of the inhibitor. Biochim Biophys Acta. 1986; 870:185-190.
﹝42﹞ Wang ZX, Tsou CL.Kinetics of substrate reaction during irreversible modification of enzyme activity for enzymes involving two substrates. J Theor Biol. 1987; 127:253-270.
﹝43﹞ Tsou CL. Kinetics of substrate reaction during irreversible modification of enzyme activity.Adv Enzymol Relat Areas Mol Biol. 1988; 61:381-436.
﹝44﹞ Lin YZ, Liang SJ, Zhou JM, Tsou CL, Wu PQ, Zhou ZK. Comparison of inactivation and conformational changes of D-glyceraldehyde-3-phosphate dehydrogenase during thermal denaturation.Biochim Biophys Acta. 1990; 1038:247-252.
﹝45﹞ Chen QX, Huang H, Kubo I. Inactivation kinetics of mushroom tyrosinase by cetylpyridinium chloride. J Protein Chem. 2003; 22:481-487.
﹝46﹞ Kim YM, Yun J, Lee CK, Lee H, Min KR, Kim Y. Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action. J Biol Chem. 2002; 3:16340-16344.
﹝47﹞ Kubo I, Kinst HI. Tyrosine inhibitors from cumin. J Agric Food Chem 1998; 46: 5338–5341.
﹝48﹞ Rheinwald JG, Green H. Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma. Cell1 1975; 6: 6317–6330.
﹝49﹞ Curto EV, Kwong C, Hermersdorfer H, Glatt H, Santis C, Virador V, Hearing VJ, Dooley TP. Inhibitors of mammalian melanocyte tyrosinase: In vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. Biochem Pharmacol 1999; 57: 663–672.
﹝50﹞ Tomita Y, Maeda K, Tagami H. Melanocyte-stimulating properties of arachidonic acid metabolites: possible role in postinflammatory pigmentation. Pigment Cell Res 1992; 5: 357–361.
﹝51﹞ Jan O, Cheng YL. Enzymatic oxidative reaction of catechin and chlorogenic acid in a model system. J Agric Food Chem 1990; 38:1202-1204.
﹝52﹞ Lin J, Mori A. Antioxidant and pro-oxidant activities of phy-droxybenzyl alcohol and vanillin: Effects on free radicals,brain peroxidation and degradation of benzoate, deoxyribose, amino acids and DNA. Neuropharmacology 1993; 32:659-669.
﹝53﹞ Xie JJ, Chen QX, Wang Q, Song KK, Qiu L. Inactivation kinetics of mushroom tyrosinase by cetylpyridinium chloride. J Protein Chem 2003; 22:481-487
﹝54﹞ Tsou CL. Kinetics of substrate reaction during irreversible modification of enzyme activity. Adv Enzymol Relat Areas Mol Biol 1988; 61:381-436.
﹝55﹞ Kubo I, Kinst HI. Flavonols from saffron flower: Tyrosinase inhibitory activity and inhibition mechanism. J Agric Food Chem 1999; 47: 4121-4125.
﹝56﹞ Kubo I, Kinst HI. Chaudhuri SK, Kuno Y, Sznchez Y, Ogira T. Heterotheca inuloides: tyrosinase inhibitory activity and structural criteria. Bioorg Med Chem 2000; 8:1749-1755.
﹝57﹞ Kahn V. Effect of kojic acid on the oxidation of Dl-DOPA, norepinephine, and dopamine by mushroom tyrosinase. Pigment Cell Res 1995;8:234- 240.
﹝58﹞ Tomita Y, Maeda K, Tagami H. Melanocyte-stimulating properties of arachidonic acid metabolites: possible role in postinflammatory pigmentation. Pigment Cell Res 1992; 5: 357–361.
﹝59﹞ Hedley SJ, Layton C, Heaton M, Chakrabarty KH, Dawson RA, Gawkrodger DJ, MacNeil S. Fibroblasts play a regulatory role in the control of pigmentation in reconstructed human skin from skin types I and II. Pigment Cell Res 2002; 15: 49–56.
﹝60﹞ Lei TC, Virador VM, Vieeira WD, Hearing VJ. A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. Anal Biochem 2002; 305: 260–268.
﹝61﹞ Kunisada T, Lu SZ, Yoshida H. Murine cutaneous mastocytosis and epidermal melanocytosis induced by keratinocyte expression of transgenic stem cell factor. J Exp Med 1998; 187: 1565–1573.
﹝62﹞ Kunisada T, Yoshida H, Yamazaki H. Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors. Development 1998; 125: 2915–2923.
﹝63﹞ Grichnik JM, Burch JA, Burchette J, Shea CR. The SCF/KIT pathway plays a. critical role in the control of normal human melanocyte homeostasis. J Invest Dermatol 1998; 111: 233–238.
﹝64﹞ Todd C, Hewitt SD, Kempenaar J, Noz K, Thody AJ, Ponec M. Co-culture of human melanocytes and keratinocytes in a skin equivalent model: effect of ultraviolet radiation.Arch Dermatol Res. 1993;285:455-9.
﹝65﹞ Yoon TJ, Hearing VJ. Co-culture of mouse epidermal cells for studies of pigmentation. Pigment Cell Res. 2003; 162:159-63.
﹝66﹞ Gibbs S, Murli S, De Boer G, Mulder A, Mommaas AM, Ponec M. Melanosome capping of keratinocytes in pigmented reconstructed epidermis--effect of ultraviolet radiation and 3-isobutyl-1-methyl-xanthine on melanogenesis.Pigment Cell Res 2000;13:458-66.
﹝67﹞ Toyoda M, Luo Y, Makino T, Matsui C, Morohashi M. Calcitonin gene-related peptide upregulates melanogenesis and enhances melanocyte dendricity via induction of keratinocyte-derived melanotrophic factors.J Investig Dermatol Symp Proc 1999;4:116-25.
﹝68﹞ Hoogduijn MJ, Smit NP, van der Laarse A, van Nieuwpoort AF, Wood JM, Thody AJ. Melanin has a role in Ca2+ homeostasis in human melanocytes.Pigment Cell Res 2003; 16:127-32.
﹝69﹞ Régnier M, Duval C, Galey JB, Philippe M, Lagrange A, Tuloup R, Schmidt R. .Keratinocyte-melanocyte co-cultures and pigmented reconstructed human epidermis: models to study modulation of melanogenesis. Cell Mol Biol 1999, 45:969-80.
﹝70﹞ Lei TC, Virador VM, Vieira WD, Hearing VJ. A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro. Anal Biochem. 2002 15:260-8.
﹝71﹞ Gordon, PR, Mansur CP, Gilchrest BA. Regulation of human melanocyte growth, dendricity and melanization by keratinocyte derived factors. J Invest Dermatol 1989; 92: 565–572.
﹝72﹞ Imokawa G, Kobayashi T, Miyagishi M, Higashi K, Yada Y. The role of endothelin-1 in epidermal hyperpigmentation and signaling mechanisms of mitogenesis and melanogenesis. Pigment Cell Res 1997; 10: 218–228.
﹝73﹞ Virador VM, Muller J, Wu X, Abdel-Malek ZA, Yu ZX, Ferrans VJ, Kobayashi N, Wakamatsu K, Ito S, Hammer JA, Hearing VJ. Influence of alpha-melanocyte-stimulating hormone and ultraviolet radiation on the transfer of melanosomes to keratinocytes. FASEB J 2002; 16: 105–107
﹝74﹞ Kippenberger S, Bernd A, Bereiter-Hahn J, Ramirez-Bosca A, Kaufmann R, Holzmann H. Transcription of melanogenesis enzymes in melanocytes: dependence upon culture conditions and co-cultivation with keratinocytes. Pigment Cell Res 1996; 9:179–184.
﹝75﹞ Chakraborty AK, Funasaka Y, Pawelek JM, Nagahama M. Enhanced expression of melanocortin-1 receptor (MC1R) in normal human keratinocytes during differentiation: evidence for increased expression of POMC peptides near suprabasal layer of epidermis. J Invest Dermatol 1999; 112: 853–860.
﹝76﹞ Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne JP, Ballotti R. Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol 1998; 142: 827–835.
﹝77﹞ Haddad MM, Xu W, Schwahn DJ. Activation of a cAMP pathway and induction of melanogenesis correlate with association of p16 (INK4) and p27 (KIP1) to CDKs, loss of E2F-binding activity, and premature senescence of human melanocytes. Exp Cell Res 1999; 253:561-572.
﹝78﹞ Goding CR. Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev 2000; 14: 1712 –1728.
﹝79﹞ Lee DY, Ahn HT, Cho KH. A new skin equivalent model: dermal substrate that combines de-epidermized dermis with fibroblast-populated collagen matrix.
J Dermatol Sci. 2000; 23:132-137.
﹝80﹞ Lee DY, Cho KH. The effects of epidermal keratinocytes and dermal fibroblasts on the formation of cutaneous basement membrane in three-dimensional culture systems. Arch Dermatol Res 2005; 296:296-302.
﹝81﹞ Maruguchi T, Maruguchi Y, Suzuki S, Matsuda K, Toda K, Isshiki N. A new skin equivalent: keratinocytes proliferated and differentiated on collagen sponge containing fibroblasts. Plast Reconstr Surg 1994; 93:537-544.
﹝82﹞ Bell E, Sher S, Hull B, Merrill C, Rosen S, Chamson A, Asselineau D, Dubertret L, Coulomb B, Lapiere C, Nusgens B, Neveux Y. The reconstitution of living skin.J Invest Dermatol 1983; 81:2-10.
﹝83﹞ Regnier M, Asselineau D, Lenoir MC. Human epidermis reconstructed on dermal substrates in vitro: an alternative to animals in skin pharmacology. Skin Pharmacol 1990; 3:70-85.
﹝84﹞ Regnier M, Caron D, Reichert U, Schaefer H. Reconstructed human epidermis: a model to study in vitro the barrier function of the skin. Skin Pharmacol 1992; 5:49-56.
﹝85﹞ Lee DY, Lee JH, Lee ES, Cho KH, Yang JM. Fibroblasts play a stimulatory role in keratinocyte proliferation but an inhibitory role in melanocyte growth and pigmentation in a skin equivalent system from skin type IV. Arch Dermatol Res 2003; 294:444-446.