DeoxyArbutin:: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency
DeoxyArbutin:: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency
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DOI：
10.1111/j.0906-6705.2005.00337.x
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
deLong, MA
中科院分区：
文献类型：
--
作者：
Boissy, RE;Visscher, M;deLong, MA
调节黑素细胞中的黑素生成可以使用与底物酪氨酸具有结构同源性的化学物质来实现，从而竞争性地抑制酪氨酸酶的催化功能。基于此，我们开发了一种新的酪氨酸酶抑制剂脱氧熊果苷（dA）。脱氧熊果苷在体外表现出对蘑菇酪氨酸酶的有效抑制，Ki比氢醌（HQ）低10倍，比熊果苷低350倍。在无毛、有色豚鼠模型中，dA表现出快速和持续的皮肤增亮，在停止局部给药后8周内完全可逆。相比之下，HQ诱导了短暂但不持续的皮肤增亮效果，而曲酸和熊果苷没有表现出皮肤增亮效果。一组安全性测试的结果支持dA作为可操作分子的总体确立。在人类临床试验中，dA局部治疗12周分别导致浅色皮肤或深色皮肤个体群体中整体皮肤亮度的显著或轻微降低和日光性雀斑的改善。这些数据表明，dA具有潜在的酪氨酸酶抑制活性，可导致皮肤增亮，并可用于改善色素沉着病变。
Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10-fold lower that hydroquinone (HQ) and 350-fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.