(-)-epigallocatech in-3-gallate and hinokitiol reduce melanin synthesis via decreased MITF production

(-)-epigallocatech in-3-gallate and hinokitiol reduce melanin synthesis via decreased MITF production
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DOI:
10.1007/bf02980069
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发表时间:
2004-03-01
影响因子:
6.7
通讯作者:
Park, KC
Park, KC
中科院分区:
医学2区
文献类型:
--
作者:
Kim, DS;Park, SH;Park, KC

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在本研究中,研究了(-)-表没食子儿茶素-3-没食子酸酯(EGCG)和/或桧木醇(β -thujapljcin)对黑色素生成的影响。我们的研究结果表明,EGCG和扁柏醇均以浓度依赖性的方式显著抑制黑色素合成,并且它们的降色素作用强于曲酸,曲酸可以抑制黑色素细胞和黑色素瘤细胞中的黑色素形成。有趣的是,EGCG在与曲酸联合使用时没有表现出任何添加剂的降色素作用,尽管EGCG与桧木醇联合使用时确实表现出协同作用。一些报道表明,细胞外信号调节激酶(ERK)的激活诱导了小眼相关转录因子(MITF)的降解。因此,我们研究了EGCG和桧木醇对ERK信号通路的影响。EGCG和扁柏醇既不激活ERK,也不降解MITF。另一方面,EGCG和桧木醇都降低了MITF和酪氨酸酶(限速黑素生成酶)的蛋白水平,而曲酸没有影响。此外,桧木醇对酪氨酸酶活性有较强的下调作用,而EGCG和曲酸对酪氨酸酶活性的下调作用较小。这些结果表明,EGCG和桧木醇都能减少MITF的产生,并表明桧木醇降低酪氨酸酶活性可以解释它们对黑色素形成的协同作用。
In this study, the effects of (-)-epigallocatechin-3-gallate (EGCG) and/or hinokitiol (beta-thujapljcin) on melanogenesis were investigated. Our results showed that both EGCG and hinokitiol significantly inhibited melanin synthesis in a concentration-dependent manner, and that their hypopigmenting effects were stronger than that of kojic acid, which is known to inhibit melanin formation in melanocytes and melanoma cells. Interestingly, EGCG did not show any additive hypopigmenting effect in combination with kojic acid, though EGCG did show a synergistic effect in combination with hinokitiol. Several reports indicate that the activation of extracellular signal-regulated kinase (ERK) induces microphthalmia-associated transcription factor (MITF) degradation. Accordingly, the effects of EGCG and hinokitiol on the ERK signaling pathway were examined. EGCG and hinokitiol induced neither ERK activation nor MITF degradation. On the other hand, both EGCG and hinokitiol reduced the protein levels of MITF and of tyrosinase, the rate limiting melanogenic enzyme, whereas kojic acid had no effect. In addition, hinokitiol strongly downregulated the activity of tyrosinase, whereas EGCG or kojic acid had only a little effect. These results show that both EGCG and hinokitiol reduce MITF production, and suggest that reduced tyrosinase activity by hinokitiol explains their synergistic effect on melanogenesis.