文献分享 I 光甘草定增强α-熊果苷局部渗透性和抗黑素生成作用的分子机制

α-Arbutin (Arb) has earned widespread attention in the whitening cosmetics, however, its poor drug permeability and short function time exert tremendous challenges for formulations. Herein, we endeavored to screen the compounds that simultaneously enhanced the topical permeability and anti-melanogenic effect of α-arbutin. Ten whitening compounds were selected to evaluate their permeation-enhancing effect to Arb on the porcine skin. We found that Glabridin (Gla) and undecylenoyl phenylalanine (UP) were superior to enhancing the skin retention of α-arbutin than other compounds, and encouraged more α-arbutin accumulation in the epidermis and dermis layers. Furthermore, Gla and UP exhibited a remarkable capability of altering the secondary conformation of keratin and inducing the disorganization of SC surface alignments, thereby achieving permeation enhancement on Arb. Molecularly, Gla and UP possessed a higher intermolecular energy with keratin than α-arbutin, as elucidated by computational simulations. Remarkably, Gla reinforced the activities of inhibiting tyrosinase and melanin production, exhibiting a synergistic whitening effect at cellular and animal pigmentation models with Arb. More importantly, Gla and Arb were biocompatible drug combination for skin whitening. Collectively, Gla was an ideal candidate for enhanced drug permeability and anti-melanogenic effect of Arb, which was a promising drug compatible in pharmaceutical and cosmetics industry.

α-熊果苷（Arb）在美白化妆品领域广受关注，然而其药物渗透性差及功效持续时间短的特性，为配方设计带来了巨大挑战。在此，我们旨在筛选出那些既能提高α-熊果苷的局部渗透性，又能增强其抗色素生成作用的化合物。选取十种美白化合物，评估其在猪皮上对α-熊果苷渗透促进的效果。研究表明光甘草定（Gla）和十一烯酰苯丙氨酸（UP）在增强α-熊果苷在皮肤中的留存方面比其他化合物效果更显著，并且能够促使更多的α-熊果苷在表皮和真皮层中积累。此外，Gla 和 UP 具有显著的能力来改变角蛋白的二级结构，并导致基底膜表面排列的紊乱，从而提高了 Arb 的渗透性。在分子层通过计算模拟可知，Gla和UP与角蛋白形成的分子间能量高于α-熊果苷。值得注意的是，Gla在细胞和动物色素沉着模型中与Arb协同发挥美白功效，显著增强了抑制酪氨酸酶活性和黑色素生成的作用。Gla与Arb这两种物质是一种适用于皮肤美白的生物相容性药物组合。总的来说，Gla 具有促进药物渗透和增强Arb抗色素生成作用的双重优势，而Arb是一种在制药和化妆品行业都颇具前景的药物。

The in vitro permeation and retention performance of Arb in the presence of different enhancers in the porcine skin within 48 h. (a) In vitro permeation pro?les and (b) Retention amount of Arb in the presence of 3-OEA, GH, PB, RG, and ADE; (c) In vitro permeation curves and (d) Accumulation amount of Arb in the presence of Glu, CD, Gla, TA, and UP; (e) Arb retention amount in SC layer and subcutaneous layers (n = 4, Data are expressed as mean values ± SD, **p < 0.01, ****p < 0.0001, compared with Arb).

α-arbutin；Permeation enhancer；Anti-melanogenic；Topical drug delivery；Glabridin

α-熊果苷   渗透促进剂   抗黑色素生成   局部药物递送   光甘草定

The molecular mechanisms underlying Glabridin enhancing the topical permeability and anti-melanogenic effect of α-arbutin.pdf