Plant oil complex: dual activation of peroxisome proliferator-activated receptors α and γ to enhance skin barrier function.

This study aimed to identify novel natural peroxisome proliferator-activated receptor (PPAR) agonists and evaluate the effects of avocado oil unsaponifiable (AOU), Ganoderma lucidum spore oil (GLSO), and Ximenia americana seed oil (XASO) on skin barrier repair at cellular and human levels, elucidating their combined mechanisms. The oils were extracted using molecular distillation, supercritical CO2 extraction, and cold pressing. PPAR activation was assessed via luciferase activity in human embryonic kidney 293 cells (HEK 293T). A blend of the three oils (AGX) was further examined in HaCaT cells using immunofluorescence. A three-dimensional (3D) human skin model was used to evaluate AGX's effects on barrier-related genes (FLG, LOR, DSG1, TGM1, CLDN1, CER). A clinical trial measured transepidermal water loss (TEWL) and stratum corneum hydration (SCH). AGX significantly activated PPARα-LBD and PPARγ-LBD transcription and upregulated FLG, LOR, DSG1, TGM1, and CLDN1 (p < 0.01). In vivo, both 2 % and 4 % AGX reduced TEWL and increased SCH (p < 0.05). AOU and XASO activated PPAR pathway genes (e.g., ANGPTL4, ILK) and downregulated MMP1. AGX repaired the skin barrier via PPAR pathways and may be a promising therapy for dermatological conditions involving barrier impairment.