BackgroundMyocardial ischemia/reperfusion (I/R) injury is the principal cause of death, happens after prolonged obstruction of the coronary arteries. The first intervention to limit myocardial damage is directed to restoration of perfusion, to avoid inflammatory response and a significant oxidative stress triggered by infarction. Palmitoylethanolamide (PEA), is a well-known fatty acid amide-signaling molecule that possess an important anti-inflammatory and analgesic effects. PEA does not hold the ability to inhibit free radicals formation. Baicalein, a bioactive component isolated from a Chinese herbal medicine, has multiple pharmacological activities, such as a strong anti-oxidative effects. PurposeA combination of PEA and Baicalein could have beneficial effects on oxidative stress produced by inflammatory response. Study designIn the present study we explored the effects of composite containing PEA and Baicalein in a model of myocardial I/R injury. MethodsMyocardial ischemia/reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-Baicalein (9:1), was administered (10 mg/kg) 5 min before the end of ischemia and 1 h after reperfusion. ResultsIn this study, we clearly demonstrated that PEA-Baicalein treatment decreases myocardial tissue injury, neutrophils infiltration, markers for mast cell activation expression as chymase and tryptase and pro-inflammatory cytokines production (TNF-α, IL-1β). Moreover, PEA-Baicalein treatment reduces stress oxidative and modulates Nf-kB and apoptosis pathways. ConclusionThese results support the idea that the association between PEA and Baicalein should be a potent candidate for the treatment of myocardial I/R injury.