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

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. 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. 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. 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 UVA-induced 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. 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. • JDY targets photoaging by regulating glutathione metabolism, activating TGF-β/Smad, and inhibiting MAPK/AP-1 pathways. • JDY reduces UVA-induced oxidative stress, enhances elastin/collagen I synthesis, and suppresses MMP-1 release. • Integrated transcriptomic and cellular assays demonstrate JDY's mechanism, supported by preliminary clinical findings.