视黄醇(维生素A,VA)在护肤品中由于不稳定而受到限制,水溶性差,和对抗皮肤老化的皮肤不耐受。我们采用计算机辅助虚拟筛选和细胞实验与转录组学,从而揭示了阿魏酸(FA)与VA协同作用的光老化HaCaT细胞的全面基因表达和调控途径。通过网络药理学分析,VA和FA的联合使用显示出与作用于EGFR的皮肤老化高度相关的交叉靶标,PTPN1,ESR2,GSK3B,BACE1,PYGL,PTGS2和APP。氧化应激的指标,如SOD,GSH,MDA,共同给药后HaCaT细胞中的CAT和ROS,与光老化组相比有显著改善(p<0.0001)。155个差异表达基因(DEGs)在组间具有特异性,而降低PTGS2的表达被确定为VA和FA光老化HaCaT细胞的重要调节因子。共同给药组的DEG专注于氧化还原酶活性,皮肤生长,角质化,和类固醇生物合成。显然,VA和FA的共同给药通过减少氧化应激损伤有效缓解UVB诱导的光老化过程,炎症反应,调节细胞生长。这种协同方法显著减慢了光老化进程并改善了VA在HaCaT细胞中的应用性能。
Application of retinol (Vitamin A, VA) in skincare is limited for instability, poor water solubility, and skin intolerance that combats skin aging. We employed computer-aided virtual screening and cell experiments with transcriptomics, thereby unveiling the comprehensive gene expression and regulation pathway of photoaging HaCaT cell treated with ferulic acid (FA) in synergizing with VA. Through network pharmacology analysis, the combined use of VA and FA exhibited highly correlated cross-targets with skin aging acting on EGFR, PTPN1, ESR2, GSK3B, BACE1, PYGL, PTGS2 and APP. The indicators of oxidative stress, such as SOD, GSH, MDA, CAT and ROS in HaCaT cells after co-administration, were significantly improved from those in photoaging group (p<0.0001). 155 differential expressed genes (DEGs) were specific between groups, while reducing the expression of PTGS2 was identified as an important regulatory factor in photoaging HaCaT cells by VA and FA. Those DEGs of co-administration group focused on oxidative-reduction enzyme activity, skin growth, keratinization, and steroid biosynthesis. Apparently, the co-administration of VA and FA effectively mitigated the process of UVB-induced photoaging by reducing oxidative stress injury, inflammation responses, and regulating cell growth. This synergistic approach significantly slowed down the photoaging progression and improved the applied performance of VA in HaCaT cells.