Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation

Abstract

Sinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo mouse model of MIRI. Adult male C57BL/6J mice received SIN (80 mg/kg) for 5 days and underwent 30 min of percutaneous occlusion of the left anterior descending artery (LAD) followed by 24 h of reperfusion. Results showed that pretreatment with SIN significantly reduced myocardial infarct size and concentrations of markers of cardiac injury and improved left ventricular ejection fraction (EF) and shortening fraction (FS) in MIRI mice. The SIN pretreatment prevented the MIRI-induced decrease in the expression levels of Bcl-2, increase in the expression levels of caspase-3, caspase-9, and Bax, and increase in the number of TUNEL-positive cells in ischemic heart tissue. It was also found that pretreatment with SIN prevented the MIRI-induced oxidative stress imbalance in ischemic heart tissue, as shown by the increase in total antioxidant capacity (T-AOC) and glutathione (GSH) and the decrease in malondialdehyde (MDA), reactive oxygen species (ROS), and dihydroethidium (DHE) density. Further studies showed that the stimulus of cardiac ischemia/reperfusion caused a remarkable increase in the expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA in ischemic heart tissue, which was effectively prevented by pretreatment with SIN. These results demonstrate that SIN can attenuate MIRI-induced cardiac injury in vivo by preventing oxidative stress, inflammation, and apoptosis.

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“…20 Sinomenine confers protection against hepatic 17 and myocardial I/R injury by preventing oxidative Stress, cellular apoptosis, and inflammation. 33 …”

Protective effect and mechanism of different proportions of “Danggui-Kushen” herb pair on ischemic heart disease

“…In this study, the HIF-1α/NF-κB signaling pathway was found to play a key role in the protective effect of DKHP on the heart. NF-κB is a key protein of the entire inflammatory family [ 29 ], a typical signaling pathway [ 30 ] responsible for the process of inflammatory infiltration and inhibition of cell survival. Phosphorylated IKβ can promote the release of NF-κB, which enters the nucleus and activates the expression of inflammatory genes [ 31 ].…”

Salvianolic acids and its potential for cardio-protection against myocardial ischemic reperfusion injury in diabetes

“…Cardiomyocytes express high levels of endoplasmic reticulum stress-related signaling proteins, including transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), glucose regulatory protein 78 (GRP78), etc. Treatments that Inhibit the signaling of endoplasmic reticulum stress can effectively reduce the rate of cell death in conditions like myocardial ischemiareperfusion injury (61)(62)(63)(64). Key cellular events in the pathogenesis of MIRI are summarized in Figure 1.…”