Protective Effect of Simplicillium sp. Ethyl Acetate Extract against High Glucose-Induced Oxidative Stress in HUVECs.

Shi-Quan Gan,Ting-Ting Tian,Qi-Rui Li,Xiang-Chun Shen,Chu-Rui Chang

doi:10.1155/2020/5172765

Abstract

This study aimed at investigating the cytoprotective effect of an ethyl acetate extract of insect fungi against high glucose- (HG-) induced oxidative damage in human umbilical vein endothelial cells (HUVECs). An insect fungus strain termed CH180672 (CH) was found for protecting HUVECs from HG-induced damage. In this study, CH was identified as Simplicillium sp. based on a phylogenetic analysis of ITS‐rDNA sequences. Ethyl acetate extract (EtOAc) of this strain (CH) was subjected to the following experiments. Cell viability was examined with the MTT method. To evaluate the protection of CH, intracellular reactive oxygen species (ROS), malondialdehyde (MDA) levels, and the activities of antioxidant enzymes were measured and the expression of oxidation-associated proteins was assessed. In the current study, it has been found that CH can increase the survival rate of HUVECs induced by HG. Additionally, we found that HG-induced nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) signal decreased and increased the intracellular ROS and MDA generation in HUVECs. However, CH treatment strongly promoted the translocation of Nrf2 and its transregulation on HO-1 and ultimately inhibited the high level of ROS and MDA induced by HG. The regulatory ability of CH was similar to Nrf2 agonist bardoxolone, while the effect was abolished by ML385, suggesting that Nrf2 mediated the inhibition of CH on HG-induced oxidative stress in HUVECs. Taken together, CH can improve HG-induced oxidative damage of HUVECs, and its mechanism may be related to the regulation of the Nrf2/HO-1 pathway.

Highlights

Diabetes mellitus (DM) is an endocrine and metabolic disorder characterized by impaired insulin secretion and increased blood glucose level [1]
It is well known that endothelial dysfunction is a key pathological progress of numerous cardiovascular diseases. erefore, we used HG to establish a human umbilical vein endothelial cells (HUVECs) injury model to screen active strains. e same concentration (32 μg/L) EtOAc extracts from 5 different strains of insect fungi was supplied into high glucose- (HG-)treated HUVECs
CH could inhibit the decrease of superoxide dismutase (SOD), CAT, and GSH levels (Figures 6(a)–6(c)). ese results indicated that CH protected oxidative stress damage of HUVECs induced by HG through cellular antioxidation system to control redox balance

Summary

Introduction

Diabetes mellitus (DM) is an endocrine and metabolic disorder characterized by impaired insulin secretion and increased blood glucose level [1]. Hyperglycemia causes many serious complications such as retinopathy, neuropathy, and nephropathy in diabetic patients [2]. It is notable that hyperglycemia causes a significant increase in reactive oxygen species (ROS) in endothelial cells, leading to cell injury and subsequent cell death [3]. It has been reported that ROS-mediated vascular stress can maintain glucose normalization in DM animals and in cultured endothelial cells. Long-term maintenance of oxidative stress results in the overactivation of pathways closely associated with DM and diabetic complications [4]. Oxidative stress is the initial link and pathological factor of endothelial damage and microvascular diseases. Reducing excessive ROS is crucial for the prevention and treatment of DM complications, especially in endothelial dysfunction and injury

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Conclusion