Anti-photoaging effects of a topical lotion mediated by coordinated modulation of glutathione metabolism,TGF-β/Smad,and MAPK pathways for extracellular matrix homeostasisOA

Background:Skin aging results from intrinsic chronological factors and harmful environmental influences,notably photoaging characterized by UV-induced oxidative stress,which disrupts extracellular matrix(ECM)homeostasis and compromises antioxidant defenses.Although numerous anti-aging cosmetic products purport to address these processes,comprehensive evaluations that integrate transcriptomics with functional cellular validation remain scarce.Objective:The present study aimed to evaluate the anti-aging efficacy of a skincare lotion(JDY)and to elucidate its molecular mechanisms of action through an integrative approach combining transcriptomic profiling,cellular assays,and preliminary clinical observations.Materials and Methods:Transcriptome sequencing of UVA-irradiated human dermal fibroblasts(HDFs)coupled with KEGG analysis identified molecular targets.Functional validation included assessments of intracellular ROS,COL1,and ELN synthesis,MMP-1 activity,and Western blot analysis.A 56-day clinical observation employing 3D imaging techniques quantified changes in wrinkle morphology and skin firmness to provide phenotypic context.Results:Transcriptomic analyses revealed three principal regulatory effects:(1)modulation of glutathione metabolism via upregulation of GSTA4 and GSTM2,conferring robust antioxidant protection;(2)activation of the TGF-β/Smad signaling pathway through increased expression of TGFBR1 and SMAD3,promoting extracellular matrix biosynthesis;(3)downregulation of MAPK/AP-1 pathway components,including FOSL1 and MMP1,thereby inhibiting collagen degradation.In vitro experiments demonstrated that JDY attenuated UVAinduced reactive oxygen species(ROS)production,enhanced ELN and COL1 synthesis by 13.0%and 14.5%,respectively,and suppressed MMP-1 release.Western blot analysis confirmed the upregulation of SMAD3 and COL1 protein expression.Consistent with these findings,clinical assessment showed JDY application improved skin elasticity parameters(R2,R5,Q1)and increased stratum corneum hydration by 31.7%,and reduced transepidermal water loss by 29.7%,with 3D skin imaging demonstrating pronounced wrinkle amelioration.Conclusion:JDY exhibits anti-photoaging properties by synergistically exerting antioxidant effects,stimulating extracellular matrix biosynthesis,and suppressing collagenolytic activity.This study defines a multifaceted molecular mechanism for JDY,with preliminary clinical observations providing supportive phenotypic context,thereby informing mechanism-driven development of anti-aging cosmetic formulations.