Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production.

Xin-Tong Wang,Shuang He,Xi Chen,Yuefei Wang,Jun-Hua Zhang,Yuxin Feng,Guangxu Xiao,Ting Shang,Yan Zhu,Ying-Ying An,Xiumei Gao,Tao Wang,Han Zhang,Zhen Peng

doi:10.3389/fphar.2020.614024

Abstract

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.

Highlights

The mortality rate in septic shock generally exceeds 40% (Beesley et al, 2018)
attenuate cytokine storm to protect the cardiac function of septic shock
It is believed that TNF-α

Summary

Introduction

The mortality rate in septic shock generally exceeds 40% (Beesley et al, 2018). Sepsis-induced cardiomyopathy (SIC), a frequent incident in sepsis, contributes to the poor outcomes of septic shock (Ehrman et al, 2018; Martin et al, 2019). Circulating proinflammatory cytokines act directly on cardiomyocytes and vasculatures to compromise myocardial performance (Ehrman et al, 2018). It is believed that TNF-α, IL-1β, and IL-6 are major contributors to SIC (Pathan et al, 2004; Liu et al, 2017; Martin et al, 2019)

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