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.
Septic liver injury remains a challenge in sepsis treatment. Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome activation has been suggested to be a major cause of hepatocyte cell death in liver diseases. However, insufficient research has been performed to explore the underlying mechanisms associated with this. In the present study, sophocarpine, a pharmaceutical monomer originally isolated from Sophora flavescens, was suggested to attenuate septic liver injury in a mouse cecal ligation and puncture (CLP) model. By utilizing western blotting, ELISA, H&E staining and immunohistochemistry, the results demonstrated that sophocarpine treatment reversed CLP-induced elevations in serum aspartate transaminase, alanine transaminase, interleukin (IL)-6 and IL-1β levels. Additionally, sophocarpine appeared to have suppressed the activation of the NLRP3 inflammasome, as indicated by observed reductions in liver IL-1β, NLRP3, caspase 1-p20 and gasdermin D-p30 protein levels. Further investigation suggested that sophocarpine-induced autophagy was essential for this suppression of NLRP3 inflammasome activation, the inhibition of which reversed the protective effects of sophocarpine on CLP-induced liver injury. Collectively, results from the present study suggested a protective role for sophocarpine against septic liver injury, where sophocarpine may suppress NLRP3 inflammasome activation by autophagy-mediated degradation.
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