Abstract

Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (Σ-ST), and reduced the scope of myocardial ischemia (N-ST). Meanwhile, SL alleviated ischemic reperfusion damage in ex vivo rat hearts with improved LVEDP and ± dp/dtmax values of the left ventricle. SL reduced the pathological changes of LDH, IL-1β, MDA, and NO contents, all of which are related to the expression of NF-κB. Further analysis by Bio-Plex array and signal pathway blocker revealed that the phosphorylation of IκB was a key factor for SL to inhibit myocardial ischemic injury, and the regulation of SL on IκB was primarily related to degradation of the IκB protein. These results provided dependable evidence that SL could protect against myocardial ischemic injury through the NF-κB signaling pathway.

Highlights

  • Cardiovascular disease (CVD) remains the leading cause of global mortality

  • At 180 min after administration, the ischemia degree of dogs treated with 66 mg/kg and 132 mg/ kg of Shenlian extract (SL) was reduced by 89% and 80%, respectively

  • Our study showed that nuclear factor kB (NF-kB) expression was significantly decreased (P < 0.05) in the SL 448 mg/kg group compared with the I/R group (Figure 4G), but there was no change in the concentration of PI3K between groups (Figure 4H)

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Summary

Introduction

Cardiovascular disease (CVD) remains the leading cause of global mortality. Ischemic heart disease (IHD), is the second leading cause of death for the Chinese population (Zhao et al, 2019), is one of the main clinical manifestations of CVD (Herrington et al, 2016). Myocardial ischemic disease has risen to a top cause of morbidity and mortality worldwide (Zhao et al, 2019). Many experimental and clinical studies support interleukin-1 beta (IL-1b) secretion, which targets vascular cells, as a promising research target to find new anti-atherosclerotic agents that better target inflammation (Hansson, 2017; Libby, 2017). Along with contemporary interventions and pharmacologic agents, traditional Chinese medicine (TCM) has been extensively prescribed in clinics in China and some Asian countries (Wang et al, 2017). TCM has attracted increasing attention around the world, because the treatment consists of significant bioactivity by multiple components (Xu et al, 2015; Zhang et al, 2015)

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