Icariside II ameliorates myocardial ischemia and reperfusion injury by attenuating inflammation and apoptosis through the regulation of the PI3K/AKT signaling pathway

Abstract

Icariside II (ICAII) is a bioflavonoid compound which has demonstrated anti-oxidative, anti-inflammatory and anti-apoptotic biological activities. However, to the best of our knowledge, whether ICAII can alleviate myocardial ischemia and reperfusion injury (MIRI) remains unknown. The aim of the present study was to determine whether ICAII exerted a protective effect on MIRI and to investigate the potential underlying mechanism of action. A rat MIRI model was established by ligation of the left anterior descending coronary artery for 30 min, followed by a 24 h reperfusion. Pretreatment with ICAII with or without a PI3K/AKT inhibitor was administered at the beginning of reperfusion. Morphological and histological analyses were detected using hematoxylin and eosin staining; the infarct size was measured using Evans blue and 2,3,5-triphenyltetrazolium chloride staining; and plasma levels of lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB) were analyzed using commercialized assay kits. In addition, the cardiac function was evaluated by echocardiography and the levels of cardiomyocyte apoptosis were determined using a TUNEL staining. The protein expression levels of Bax, Bcl-2, cleaved caspase-3, interleukin-6, tumor necrosis factor-α, PI3K, phosphorylated (p)-PI3K, AKT and p-AKT were analyzed using western blotting analysis. ICAII significantly reduced the infarct size, decreased the release of LDH and CK-MB and improved the cardiac function induced by IR injury. Moreover, ICAII pretreatment significantly inhibited myocardial apoptosis and the inflammatory response. ICAII also upregulated the expression levels of p-PI3K and p-AKT. However, the protective effects of ICAII were abolished by an inhibitor (LY294002) of the PI3K/AKT signaling pathway. In conclusion, the findings of the present study suggested that ICAII may mitigate MIRI by activating the PI3K/AKT signaling pathway.

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis

“…This study demonstrated that HSYA can significantly attenuate HR-induced AST, CK-MB, and LDH levels in a dose-dependent manner. Apoptosis, a characteristic change occurring in MI/RI, is induced through several mechanisms, including the death Oxidative Medicine and Cellular Longevity receptor pathway, mitochondrial apoptosis pathway, and endoplasmic reticulum stress pathway [34][35][36]. Here, TUNEL and JC-1 staining revealed that the protective effect of HSYA against MI/RI is related to the inhibition of apoptosis.…”

Epithelial-Mesenchymal Transition-Related lncRNAs And SNAI2 Are Potential Biomarkers in Coronary Artery Disease

“…These studies have con rmed that activating the PI3K/Akt signaling pathway can prevent myocardial ischemia-reperfusion in animal models. Other studies have also suggested that regulation of the PI3K/Akt signaling pathway plays a vital role in inhibiting myocardial brosis, apoptosis, and the in ammatory response [31,32].…”

miR-129 Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the Expression of PTEN in Rats

“…The common and worst consequence of MIRI is myocardial cell death that was associated with the inhibition of antiapoptotic signaling pathways [ 3 ]. Among them, Akt signaling pathways are involved in many cellular physiological processes and have important roles in cell survival [ 4 ]. Amounted evidences demonstrated that MIRI contributes to the decrease of phosphorylation of AKT in myocardial cell [ 4 , 5 ].…”

“…Among them, Akt signaling pathways are involved in many cellular physiological processes and have important roles in cell survival [ 4 ]. Amounted evidences demonstrated that MIRI contributes to the decrease of phosphorylation of AKT in myocardial cell [ 4 , 5 ]. Thereby, elucidation of the molecular mechanism of decreased AKT phosphorylation in MIRI is very important for the knowing of myocardial infarction as well as its therapy.…”