Puerarin Prevents Acute Liver Injury via Inhibiting Inflammatory Responses and ZEB2 Expression.

Junfa Yang,Lingling Zhang,Hui Fang,Yue Su,Huan Zhou,Maomao Wu

doi:10.3389/fphar.2021.727916

Abstract

Puerarin, an isoflavone component extracted from herb radix puerariae, is widely used in China in the treatment of immune diseases and inflammation. Previous studies have demonstrated that puerarin prevented acute lung injury by regulating inflammatory responses. However, the effect of puerarin on acute liver injury (ALI) was unclear. The purpose of this study was to explore the beneficial effects of puerarin when applied to ALI. We found that puerarin inhibited liver injury and inflammatory cell infiltration in lipopolysaccharide (LPS)/D-galactose (D-Gal)-induced acute liver failure and the liver pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in liver tissues with ALI and LPS-induced L-02 cells but upregulated the expression level of zinc finger E-box-binding homeobox 2 (ZEB2). Significantly, the results of this study showed that the inhibition of liver pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) production in LPS-induced L-02 cells was caused by ZEB2 overexpression. However, knocking down ZEB2 promoted LPS-mediated secretion of liver pro-inflammatory cytokines in L-02 cells. Additional experiments showed that puerarin inhibited the activation of the NF-κB signaling pathway by elevating ZEB2 expression in L-02 cells. In summary, puerarin most likely prevented activation of the pro-inflammatory factors and reduced LPS/D-Gal-induced liver injury by enhancing the ZEB2 expression level and, consequently, blocking activation of the NF-κB signaling pathway in the liver.

Highlights

As a key organ in the maintenance of energy balance, metabolic homeostasis, immune regulation, protein synthesis, and detoxification (Taub, 2004), the liver plays a leading role in drug metabolism and defense against infections, and is usually damaged as a result of drug overdose and/or severe infections (Lofthus et al, 2012)
We confirmed that the expression of IL-1β, TNF-α, and IL-6 could be inhibit by puerarin, thereby attenuating the LPS-induced inflammatory response of L-02 cells and LPS/D-Gal-induced Acute liver injury (ALI)
The expression of zinc finger E-box-binding homeobox 2 (ZEB2) was downregulated in ALI, while it was upregulated by puerarin

Summary

Introduction

As a key organ in the maintenance of energy balance, metabolic homeostasis, immune regulation, protein synthesis, and detoxification (Taub, 2004), the liver plays a leading role in drug metabolism and defense against infections, and is usually damaged as a result of drug overdose and/or severe infections (Lofthus et al, 2012). Other studies have shown that inflammatory responses play a critical role in ALI pathogenesis (Yang et al, 2020). The results of recent studies have shown that the pathogenesis of ALI can be blocked by the inhibition of inflammatory responses (Starkey Lewis et al, 2020). Anti-inflammatory therapies are effective in treating ALI (Chen et al, 2020; Zhang et al, 2020). It is, necessary to clarify the underlying mechanism of effective targets for ALI caused by sepsis in view of the fact that there is no current effective treatment for ALI (Bae et al, 2018)

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