Abstract

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 MMP1 and MMP7 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.

Highlights

  • Published: 15 August 2021L-Ascorbic acid (AA) is essential for skin health and nutritional deficiency of this vitamin leads to the well-characterized skin fragility and bruising seen in scurvy [1,2]

  • Topical AA delivery has been reported to improve some aspects of intrinsic skin aging [11,12,13], stronger evidence supports a role for AA in the antioxidant-mediated prevention of extrinsic aging due to UV radiation exposure [14,15,16]

  • We evaluated the effects of Tetrahexyldecyl Ascorbate (THDC), acetyl zingerone (AZ), and THDC + AZ using cell-free in vitro assays and reconstituted human epidermis (RHE) tissues (EpiDermFTTM)

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Summary

Introduction

Published: 15 August 2021L-Ascorbic acid (AA) is essential for skin health and nutritional deficiency of this vitamin leads to the well-characterized skin fragility and bruising seen in scurvy (hypovitaminosis C) [1,2]. The role of AA may parallel that of calcium [8], with pro-differentiation effects that improve barrier function through elevation of filaggrin and normalization of the stratum corneum structure [9]. Such effects are accompanied by an increased abundance of stratum corneum barrier lipids, including glucosylceramides, ceramides, and lipid lamellar structures [10]. These observations have prompted the development of topical formulations with the goal of directly delivering AA to skin to achieve cosmetic or therapeutic effects. Further evidence has supported a role for topically-applied AA or Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

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