Lycium barbarum polysaccharides inhibit ischemia/reperfusion-induced myocardial injury via the Nrf2 antioxidant pathway

Abstract

Oxidative stress is considered to be one of main pathophysiological mechanisms in myocardial ischemia/reperfusion (I/R) injury. <i>Lycium barbarum</i> polysaccharides (LBP), the main ingredient of <i>Lycium barbarum</i>, have potential antioxidant activity. We aimed to investigate the effects of LBP on myocardial I/R injury and explore the underlying mechanisms. Myocardial I/R group was treated with or without LBP to evaluate oxidative stress markers and the role of Nrf2 signal pathway. Our results showed that I/R increased infarct size and the activities of creatine kinase (CK) and lactate dehydrogenase (LDH) when compared with control group. Meanwhile, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were enhanced and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were decreased. These changes were associated with a significant increase in myocardial apoptosis, ultimately leading to cardiac dysfunction. LBP reduced infarct size (38.4 ± 2 % <i>versus</i> 19.4 ± 1.8 %, <i>p < 0.05</i>), CK and LDH activities and myocardial apoptotic index. Meanwhile, LBP suppressed the production of ROS and restored redox status. Additionally, LBP increased protein level of nuclear Nrf2 <i>in vivo</i> (2.1 ± 0.3 <i>versus</i> 3.8 ± 0.4, <i>p < 0.05</i>) and <i>in vitro</i> (1.9 ± 0.2 <i>versus</i> 3.8 ± 0.1, <i>p < 0.05</i>) and subsequently upregulated heme oxygenase 1 and NADPH dehydrogenase quinone 1 compared to I/R group. Interestingly, Nrf2 siRNA abolished the protective effects of LBP. LBP suppressed oxidative stress damage and attenuated cardiac dysfunction induced by I/R <i>via</i> activation of the Nrf2 antioxidant signal pathway.