Abstract

Sepsis-induced systemic inflammation can induce cardiac dysfunction, which can result in heart failure and death. Recently, natural drugs/compounds have received increased attention as therapeutic agents to prevent sepsis-induced cardiac dysfunction. Crocetin (CRO) is a natural compound that has been shown to reduce inflammation and cytotoxicity in cardiac ischemia/reperfusion injury. However, the effects of CRO on sepsis-induced cardiac dysfunction have not been evaluated. In this study, we used lipopolysaccharide (LPS)-induced H9c2 cells as an in vitro model to mimic cardiac sepsis. Crocetin significantly alleviated LPS-induced cytotoxicity, cellular apoptosis, and oxidative stress through increased Bcl-2 activity and PI3K-Akt signaling and suppression of caspase 3 and caspase 9 activities. Furthermore, CRO dramatically decreased the mRNA levels of TNF-α, IL-1, IL-6, and IL-8 via suppression of p65/Keap1 signaling and activation of Nrf2/HO-1/NQO1 signaling. In addition, CRO protected mitochondrial respiration, free fatty acid β-oxidation, and mitochondrial morphology in LPS-induced H9c2 cells. This study showed that CRO attenuated LPS-induced cardiac dysfunction via regulation of the inflammatory response and mitochondrial function and potentially had an effect on sepsis-induced cardiac dysfunction.

Highlights

  • Sepsis is a systemic infection in organs that is spread in blood and is often described as “blood poisoning.” The host response to sepsis is characterized by proinflammatory and anti-inflammatory responses (Angus and van der Poll, 2013)

  • The results showed that CRO significantly upregulated the activities of superoxide Dismutase (SOD) and GSH-Px and reduced the level of MDA in LPS-induced H9c2 cells (Figures 1D–F)

  • Our study showed that CRO protected against LPS-induced cardiac dysfunction in an in vitro cell model with H9c2 cardiomyocytes, which may have been due to inhibition of inflammation (Nam et al, 2010; Song et al, 2016) and regulation of mitochondrial function (Venkatraman et al, 2008)

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Summary

Introduction

Sepsis is a systemic infection in organs that is spread in blood and is often described as “blood poisoning.” The host response to sepsis is characterized by proinflammatory and anti-inflammatory responses (Angus and van der Poll, 2013). Sepsis is a systemic infection in organs that is spread in blood and is often described as “blood poisoning.”. Myocardial depression is a well-characterized manifestation of organ dysfunction and severe inflammation in sepsis and can contribute to septic death (Rudiger and Singer, 2007; Essandoh et al, 2015). Several important inflammatory genes and factors have been shown to participate in sepsis, in cardiac sepsis. The nucleotide-binding oligomerization domain-like receptor with pyrin domain (NLRP3) inflammasome and IL-1β have been shown to be Crocetin Attenuates Sepsis-Induced Cardiac Dysfunction expressed at high levels in a cecal ligation and puncture (CLP) sepsis model. Treatment with an IκB kinase inhibitor attenuated sepsisinduced cardiac dysfunction with chronic kidney disease (CKD) via reduced expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) (Chen et al, 2017)

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