Safflower Seed Oil Ameliorates AFL-Induced Epidermal Lipid Loss Partially via the PPARγ Signaling Pathway

Objective: Ablative fractional laser (AFL) therapy impairs epidermal barrier integrity through the disruption of stratum corneum lipids and keratinocyte differentiation, resulting in increased transepidermal water loss (TEWL) and delayed functional recovery. This study aims to develop a more effective barrier repair strategy and evaluate the efficacy of topical safflower seed oil (SSO) in promoting post-AFL barrier restoration. Methods: An optimized murine AFL model (20 W, 0.5 ms pulse delay, and 0.7 mm spot spacing) was established to investigate skin repair mechanisms. SSO composition was characterized by gas chromatography–mass spectrometry (GC-MS). Epidermal repair was assessed using confocal laser scanning microscopy, while Oil Red O staining and immunofluorescence were employed to evaluate lipid formation and the expression of lipid synthesis-related genes, respectively. Results: GC-MS analysis identified SSO as a rich natural source of linoleic acid (69.1%) and oleic acid (18.7%). Over the 7-day period of AFL exposure alone, TEWL rose by 4–6 fold in mouse skin, accompanied by a near-complete loss of epidermal lipid synthesis. However, upon SSO administration, a marked reduction in TEWL was observed from day 1, and epidermal lipid synthesis recovered by day 7. Moreover, SSO treatment significantly upregulated epidermal PPARγ expression in AFL-injured skin. Pharmacological inhibition of PPARγ (T0070907) largely abrogated the lipid synthesis and barrier repair effects of SSO, while PPARα antagonism (GW6471) showed no obvious interference with SSO’s therapeutic efficacy, suggesting a potential association between PPARγ signaling modulation and SSO-mediated skin barrier restoration. Conclusions: These findings suggest that SSO is a promising natural agent for post-AFL skin care, which improves AFL-impaired skin barrier function by remodeling lipid metabolism, at least in part through PPARγ signaling, and warrants further preclinical and clinical investigation.