According to Sytheon, acetyl zingerone (AZ) is a recently designed molecule that shares structural features with zingerone (Z) but has improved stability and antioxidant function. This study utilized microarrays to compare effects of Z and AZ on gene expression in reconstituted human epidermis. Both Z and AZ increased Notch pathway gene expression (NOTCH1, MAML3) and decreased expression of genes linked to extracellular matrix disassembly (MMP3, CTSV) and reactive oxygen species metabolism (PMAIP1, ARG2). Although Z and AZ each inhibited in vitro MMP-1, MMP-3 and MMP-12 activity, inhibition of MMP-3 and MMP-12 was greater with AZ. Moreover, AZ led to more consistent increases in the expression of genes encoding collagens, proteoglycans and ECM glycoproteins. Finally, AZ opposed gene expression patterns associated with fibroblast senescence, keratinocyte differentiation and IL-17A stimulation. These effects were AZ-specific and not replicated by Z.
These results show that AZ improves extracellular matrix integrity with retinoid-like effects on differentiation and inflammation. The findings provide rationale for clinical studies to understand benefits of AZ in the treatment or prevention of skin aging, or potentially, as a treatment for other human skin diseases.