Secoisolariciresinol Diglucoside Exerts Anti-Inflammatory and Antiapoptotic Effects through Inhibiting the Akt/IκB/NF-κB Pathway on Human Umbilical Vein Endothelial Cells.

Shaoyang Zhang,Meili Cheng,Yuhua Ren,Xue Wang,Zhen Wang,Shikuo Rong,Yuzhi Liu

doi:10.1155/2020/3621261

Abstract

Inflammation is a key regulator in the progression of atherosclerosis (AS) which extremely affects people's health. Secoisolariciresinol diglucoside (SDG), a plant lignan, is relevant to angiogenesis and cardioprotection against ischemia-reperfusion injury and improves vascular disorders. However, the effect of SDG on cardiovascular disorder is not clear. In the present study, we aimed to investigate the effects of SDG on lipopolysaccharide- (LPS-) stimulated Human Umbilical Vein Endothelial Cells (HUVECs) and elucidate the underlying mechanism. The LPS-stimulated HUVEC cellular model was established. The cell viability, the cell tube formation activity, the nitric oxide (NO) release, the levels of inflammatory cytokine interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the activation of nuclear factor kappa-B (NF-κB) pathway, and the expression of protein kinase B (Akt) were determined using Cell Counting Kit-8, cell tube-formation assay, western blotting, and enzyme-linked immunosorbent assay. Our results revealed that SDG reduces the angiogenic capacity of HUVECs and inhibited LPS-mediated HUVEC injury and apoptosis. In addition, SDG increased NO release and decreased the levels of IL-1β, IL-6, and TNF-α in LPS-treated HUVECs. Meanwhile, SDG inhibited the NF-κB pathway and downregulated Akt expression in LPS-induced HUVECs. Our results indicated that SDG relieves LPS-mediated HUVEC injury by inhibiting the NF-κB pathway which is partly dependent on the disruption of Akt activation. Therefore, SDG exerts its cytoprotective effects in the context of LPS-treated HUVECs via regulation of the Akt/IκB/NF-κB pathway and may be a potential treatment drug for cardiovascular disease.

Highlights

Atherosclerosis (AS) is the underlying cause of cardiovascular and cerebrovascular disease, resulting in high rates of mortality worldwide [1]
The data showed that Secoisolariciresinol diglucoside (SDG) did not exhibit toxicity at lower doses (p > 0:05; Figure 1(a)) and did not induce cell toxicity when its concentration is lower than 10 μM (p > 0:05; Figure 1(b))
We revealed that SDG inhibited LPS-mediated Human Umbilical Vein Endothelial Cells (HUVECs) injury and apoptosis

Summary

Introduction

Atherosclerosis (AS) is the underlying cause of cardiovascular and cerebrovascular disease, resulting in high rates of mortality worldwide [1]. Inflammation can alter arterial biology of atherosclerosis and produce a systemic environment conducive to AS and leads to AS and aggravate the disease [2]. Inflammation can drive arterial hyperplasia, regulate plaque formation, and trigger thrombotic complications of atherosclerosis [3]. The damage caused by inflammation and its associated cell apoptosis in endothelial cells provides important insights into the initiation of AS lesions [4]. Developing new drugs to treat AS through the inflammatory route is a good direction. Dysregulation of the immune inflammatory response system in vascular endothelial cells produces proinflammatory cytokines and immune protein mediators that trigger

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