Cuminaldehyde alleviates inflammation in isoproterenol-induced acute myocardial infarction through Nrf-2/HO-1 and NF-κB signaling pathways

Myocardial infarction (MI) is a leading cause of death, and the limited efficacy of current treatments pushes the exploration of novel drug candidates.The purpose of this study was to assess the anti-inflammatory effects of cuminaldehyde, a monocyclic terpenoid, in an in vivo model of isoproterenol-induced acute myocardial infarcted rats.Rats were induced to undergo MI by isoproterenol(100 mg/kg body weight).Then, rats were treated with cuminaldehyde (20 mg/kg body weight) daily for three weeks.Cardiac oxidative stress and inflammation were investigated. Moreover, nuclear factor (erythroid-derived-2)-like 2(Nrf-2)/heme oxygenase-1(HO-1) and nuclear factor kappa B (NF-κB)/tumor necrosis factor-alpha(TNF-α)/interleukin-6(IL-6)/interleukin-8(IL-8)/inducible nitric oxide synthase (iNOS)/cyclooxygenase-2(COX-2)-mediated signaling pathways were evaluated to unravel the molecular mechanisms of cuminaldehyde.The serum cardiac diagnostic markers and heart thiobarbituric acid reactive substances were increased, and heart glutathione peroxidase and reduced glutathione were reduced in isoproterenol-induced myocardial infarcted rats.RT-PCR analysis revealed a reduction in myocardial expression of the Nrf-2 and HO-1 genes.Isoproterenol also elevated plasma total homocysteine and serum high-sensitivity C-reactive protein.Furthermore,ELISA and RT-PCR results revealed elevated serum and myocardial expression of NF-κB, TNF-α, IL-6, IL-8, iNOS, and COX-2 in MI rats.The 2,3,5-triphenyltetrazolium chloride (TTC) staining of the heart revealed an increased myocardial infarct area in MI rats.Moreover, histopathology revealed inflammatory infiltration in the hearts of myocardial infarcted rats.Nevertheless,cuminaldehyde attenuated all the aforementioned biochemical,RT-PCR, TTC, and histopathological parameters investigated, inhibited oxidative stress, and thereby reduced isoproterenol-induced inflammation by modulating Nrf-2/HO-1 and NF-κB/TNF-α/IL-6/IL-8/iNOS/COX-2 signaling pathways through its antioxidant and anti-inflammatory effects.Additionally,it reduced myocardial infarct size by anti-myocardial infarct size effects.Thus, cuminaldehyde alleviated inflammation in isoproterenol-induced acute MI.