In Vitro Antioxidant and Cellular Activities of Functionalized Spermidine by Conjugating with Ascorbic Acid in Human Skin Cells

Spermidine (SPMD) is essential for numerous cellular functions and crucial for sustaining diverse biological activities. However, its antioxidant capabilities are relatively weak. In this study, we overcame this limitation by examining the antioxidant and cellular effects of ascorbic acid (AA)-conjugated spermidine (AA-SPMD) in human skin keratinocyte and fibroblast cells. AA-SPMD was successfully fabricated using an optimized design and synthetic approach, and its stability, antioxidant activity, cellular responses, and collagen I production were evaluated. In addition, we assessed the protective effects of AA-SPMD from hydrogen peroxide and UVA-induced oxidative damage in human skin cells. The AA-SPMD showed high stability under rigorous conditions and exhibited strong antioxidant activity. AA-SPMD showed no cytotoxic effect even at a concentration of 1 mM. In addition, it can increase the rate of cell proliferation and migration in skin cells without reducing the inhibition of human keratinocytes (HaCaT) and human dermal fibroblasts (HDF) at concentrations of 10 μM. Moreover, AA-SPMD can increase the amount of collagen I synthesized in HDF cells, thereby influencing cell proliferation and migration. Based on our in vitro study, AA-SPMD is expected to be more effective than AA or SPMD alone, indicating its potential utility in biomedical and cosmetic applications.