Abietic acid inhibits UVB‐induced MMP‐1 expression in human dermal fibroblast cells through PPARα/γ dual activation

Peroxisome proliferator‐activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand‐activated transcription factors and consist of three isotypes: PPARα, PPARβ/δ and PPARγ. PPARs are expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, these receptors are highly studied in dermato‐endocrine research, and their ligands are targets for the treatment of various skin disorders, such as photoageing and chronological ageing of skin. Intensive studies have revealed that PPARα/γ functions in photoageing and age‐related inflammation by regulating matrix metalloproteinases (MMPs) via nuclear factor‐kappa B (NF‐κB) and activator protein‐1 (AP‐1). However, the detailed mechanism of PPARα/γ's role in photoageing has not yet been elucidated. In this study, we confirmed that abietic acid (AA) is a PPARα/γ dual ligand and significantly decreased UVB‐induced MMP‐1 expression by downregulating UVB‐induced MAPK signalling and downstream transcription factors, subsequently reducing IκBα degradation and blocking NF‐κB p65 nuclear translocation in Hs68 human dermal fibroblast cells. Treatment of cells with AA and GW6471 or bisphenol A diglycidyl ether (BADGE), PPARα or PPARγ antagonists, respectively, reversed the effect on UVB‐induced MMP‐1 expression and inflammatory signalling pathway activation. Taken together, our data suggest that AA acts as a PPARα/γ dual activator to inhibit UVB‐induced MMP‐1 expression and age‐related inflammation by suppressing NF‐κB and the MAPK/AP‐1 pathway and can be a useful agent for improving skin photoageing.