Enzymatic Synthesis of a Novel α-Linolenic Acid-Enriched Phytoceramide From Perilla Seed Oil and Its Multifunctional Bioactivity in Skin Barrier Repair and Anti-Aging.

Ceramides are essential lipid components of the skin barrier, accounting for approximately 50% of intercellular lipids in the stratum corneum. Their deficiency is associated with various skin disorders, including atopic dermatitis and xerosis. This study aimed to enzymatically synthesize a novel phytoceramide from perilla seed oil (PSO-Cer) and evaluate its multifaceted bioactivity, including skin barrier enhancement and anti-aging effects, in comparison with oleic acid-derived Ceramide IIIB. PSO-Cer was synthesized enzymatically and characterized by HPLC-CAD and LC-QTOF. Its biological effects were assessed in human keratinocytes (HaCaT) and dermal fibroblasts-adult (HDF-a) through cytotoxicity assays, qPCR of genes related to barrier function and extracellular matrix (ECM) synthesis, western blot, and transcriptome sequencing. HPLC-CAD confirmed PSO-Cer was rich in polyunsaturated fatty acid chains, notably α-linolenic acid (34.49%). Both PSO-Cer and Ceramide IIIB were non-cytotoxic up to 25 µg/mL and significantly upregulated genes critical for epidermal barrier function (FLG, IVL, TGM1, CERS3, and ELOVL4) and ECM components (COL1A1, COL3A1, and ELN) in UVB-irradiated fibroblasts. Transcriptome analysis revealed that while both ceramides shared common mechanisms, namely activation of mTOR signaling and sphingolipid metabolism, PSO-Cer exhibited distinct properties, positioning it as a promising multifunctional active for advanced skincare formulations aimed at comprehensive skin health.