Tetrahexyldecyl Ascorbate (THDC) Degrades Rapidly under Oxidative Stress but Can Be Stabilized by Acetyl Zingerone to Enhance Collagen Production and Antioxidant Effects

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 degrada-tion, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antiox-idant. 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. Gene expression profiling was performed using reconstituted human epidmeris (RHE, EpiDermFT™) tissues (MatTek, Ashland, MA; cat no. EFT-400, lot no. 29376). The experiment included 4 treatments with 5 replicates each (CTL = control, THDC = tetrahexyldecyl ascorbate, AZ = acetyl zingerone; THDC + AZ = tetrahexyldecyl ascorbate with acetyl zingerone in a 1:1 ratio). The samples were divided into two batched during the RNA extraction step (batch 1 and 2).