Chamazulene Induces Metabolic Reprogramming and Mitigates Inflammation in Photoaged Skin: PPARα/γ as Potential Regulators

Chamazulene (CHA) is a brilliant blue compound present in <i>Artemisia sieversiana</i> Ehrhart ex Willd. essential oil (AEO). We have previously reported that both CHA and AEO can shield the skin from UVB damage, exhibiting significant anti-photoaging effects. However, the molecular mechanisms underlying CHA's photoprotective properties are still unclear. Herein, we integrated transcriptomics, targeted fatty acid profile, and untargeted metabolomics analyses on the dorsal skin of mice exposed to UVB with or without 0.4% CHA topical treatment. The results showed that CHA upregulated key genes involved in fatty acid metabolism, including two peroxisome proliferator-activated receptor (PPAR) subtypes, i.e., PPARα and PPARγ, in mouse skin. The CHA treatment elevated levels of various saturated, monounsaturated, and polyunsaturated fatty acids, and it especially restored n-3/n-6 polyunsaturated fatty acid homeostasis and downregulated the p38 MAPK/COX-2 pathway. Additionally, CHA enhanced skin non-essential amino acid metabolism, likely via PPARα. In conclusion, our study indicates that CHA may mitigate UVB-induced photoaging by inducing metabolic reprogramming and suppressing inflammation, and the findings suggest that the activation of PPARα/γ may play a vital role in these observed effects, thereby establishing CHA as a promising topical agent against UVB-induced photoaging.