Effects of Triacetin on AMPK Activation and Immune Responses in Allergic Contact Dermatitis

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Background/Objectives: Allergic contact dermatitis (ACD), an inflammatory skin condition, is commonly treated with topical corticosteroids; however, long-term use of these drugs is associated with various risks, such as skin atrophy and steroid resistance. Triacetin (TA), a triglyceride metabolized to acetate, exerts anti-inflammatory affects by activating AMP-activated protein kinase (AMPK) and suppressing mast cell degranulation. Here, we aimed to assess the immediate and long-term effects of TA on ACD suppression, focusing on AMPK activation, using a 2,4-dinitrofluorobenzene-induced rodent model. Methods: Various concentrations of TA were topically applied to rats with 2,4-dinitrofluorobenzene-induced dermatitis. Ear thickness was measured, and histological analysis was performed to assess the inflammation, mast cell infiltration, and degranulation in the established models. AMPK activation was analyzed via Western blotting, and TA degradation was assessed via gas chromatography-mass spectrometry. Dorsomorphin (an AMPK inhibitor) was used to evaluate the effects of AMPK on ACD. Results: TA significantly inhibited inflammation and mast cell degranulation in a dose-dependent manner, with 0.25 mmol/L showing the most potent effects. It also activated AMPK activation. Notably, AMPK inhibition reversed the effects of TA. Conclusions: Overall, TA exerted immediate and long-term anti-inflammatory effects via AMPK activation and inhibition of mast cell degranulation, showing potential as a non-steroidal therapeutic for ACD.