Department of Internal Medicine, The Jewish Hospital, Cincinnati, OH 45236, USA.
Sytheon Ltd., Boonton, NJ 07005, USA.
Int J Mol Sci. 2021 Aug 15;22(16):8756. doi: 10.3390/ijms22168756.
Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degradation, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antioxidant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of and expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.
四己基癸醇抗坏血酸酯(THDC)是一种 L-抗坏血酸前体,具有提高的稳定性和穿透表皮的能力。然而,THDC 的稳定性和经皮渗透可能会受到富含氧化剂的人体皮肤环境的影响。在这项研究中,我们表明 THDC 是一种较差的抗氧化剂,当其暴露于单线态氧时会迅速降解。然而,这种降解可以通过与乙酰氧基香豆素(AZ)结合作为稳定的抗氧化剂来预防。作为单一成分,THDC 导致 I 型干扰素信号通路的意外激活,但在 AZ 存在下,这种促炎作用被减弱。此外,THDC 和 AZ 的组合增加了与磷脂动态平衡和角蛋白细胞分化相关的基因的表达,同时抑制了 和 的表达,抑制 MMP 酶活性,并增加真皮成纤维细胞胶原蛋白蛋白的产生。最后,虽然 THDC 单独降低了暴露于氧化应激的角质形成细胞的活力,但通过向 THDC 中添加 AZ,这种作用完全被消除。这些结果表明,AZ 是 THDC 的有效抗氧化稳定剂,这些产品的组合可能会改善抗坏血酸的递送。这朝着充分发挥抗坏血酸作为局部制剂中活性成分的潜力迈出了一步。