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RETRACTED ARTICLE

Cytoprotective effects of euxanthone against ox-LDL-induced endothelial cell injury is mediated via Nrf2.
Life Sci. 2019 Apr 15; 223:174-184.LS

Abstract

AIM

Atherosclerosis (AS) is a chronic condition of the arterial vessels and a risk factor for myocardial infarction and stroke. Euxanthone is a xanthone compound extracted from Polygala caudata, and shows vasodilatory action. The aim of this study was to determine the potential pharmacological effects of euxanthone against oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury.

MATERIAL AND METHODS

Human umbilical vein endothelial cells (HUVECs) were exposed to ox-LDL, following pre-treatment with different concentrations of euxanthone. Viability, apoptosis and DNA fragmentation were respectively assessed by CCK-8 assay, Annexin-V/PI staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. The cellular levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were analyzed by enzyme linked immune-sorbent assays (ELISA), and reactive oxygen species (ROS) levels using dichlorodihydrofluorescin diacetate (DCFH) staining. Quantitative RT-PCR and Western blotting were respectively used to analyze the expression levels of specific mRNAs and proteins. HUVECs were transfected with Nrf2 siRNA to induce knockdown of the latter.

KEY FINDINGS

Euxanthone pre-treatment rescued the HUVECs from ox-LDL-induced cytotoxicity, apoptosis and DNA fragmentation in a dose-dependent manner. In addition, euxanthone also significantly reversed ox-LDL-triggered loss of mitochondrial membrane potential (MMP), cytochrome C release from mitochondria to cytosol, cleavage of caspase-3 and PARP, and increase in Bax/Bcl-2 ratio. Pre-treatment with euxanthone markedly suppressed ox-LDL-induced ROS generation and inhibition of antioxidant enzymes, as well as the up-regulation of pro-inflammatory factors like MCP-1, IL-1β and TNF-α in the HUVECs. Euxanthone up-regulated and activated Nrf2 by repressing Keap1, and increased the expression of its downstream genes HO-1 and NQO-1. Nrf2 knockdown abrogated the cyto-protective, anti-apoptotic, anti-oxidant and anti-inflammatory effects of euxanthone in ox-LDL-treated HUVECs. Finally, euxanthone activated Nrf2 via the MAPK pathway and blocking the latter likewise negated the protective effects of euxanthone against cell ox-LDL.

SIGNIFICANCE

Euxanthone protected HUVECs against the oxidative and inflammatory damage induced by ox-LDL, indicating its potential as a novel therapeutic agent for AS.

Authors+Show Affiliations

School of Pharmacy, Qingdao University, Qingdao, China; The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, China.School of Pharmacy, Qingdao University, Qingdao, China. Electronic address: yongsunqdup@126.com.The Affiliated Hospital of Qingdao University, Qingdao, China.The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao, China.Qingdao Food and Drug Inspection Institute, Qingdao, China.Qingdao Central Hospital, Qingdao, China.

Pub Type(s)

Journal Article
Retracted Publication

Language

eng

PubMed ID

30890405

Citation

Li, Shengnan, et al. "Cytoprotective Effects of Euxanthone Against ox-LDL-induced Endothelial Cell Injury Is Mediated Via Nrf2." Life Sciences, vol. 223, 2019, pp. 174-184.
Li S, Sun Y, Han Z, et al. Cytoprotective effects of euxanthone against ox-LDL-induced endothelial cell injury is mediated via Nrf2. Life Sci. 2019;223:174-184.
Li, S., Sun, Y., Han, Z., Bu, X., Yu, W., & Wang, J. (2019). Cytoprotective effects of euxanthone against ox-LDL-induced endothelial cell injury is mediated via Nrf2. Life Sciences, 223, 174-184. https://doi.org/10.1016/j.lfs.2019.03.032
Li S, et al. Cytoprotective Effects of Euxanthone Against ox-LDL-induced Endothelial Cell Injury Is Mediated Via Nrf2. Life Sci. 2019 Apr 15;223:174-184. PubMed PMID: 30890405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytoprotective effects of euxanthone against ox-LDL-induced endothelial cell injury is mediated via Nrf2. AU - Li,Shengnan, AU - Sun,Yong, AU - Han,Zhiwu, AU - Bu,Xiaocui, AU - Yu,Weijie, AU - Wang,Junyu, Y1 - 2019/03/16/ PY - 2018/12/15/received PY - 2019/03/13/revised PY - 2019/03/15/accepted PY - 2019/3/21/pubmed PY - 2019/4/18/medline PY - 2019/3/21/entrez KW - Atherosclerosis KW - ERK KW - Euxanthone KW - Nrf2 SP - 174 EP - 184 JF - Life sciences JO - Life Sci. VL - 223 N2 - AIM: Atherosclerosis (AS) is a chronic condition of the arterial vessels and a risk factor for myocardial infarction and stroke. Euxanthone is a xanthone compound extracted from Polygala caudata, and shows vasodilatory action. The aim of this study was to determine the potential pharmacological effects of euxanthone against oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury. MATERIAL AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to ox-LDL, following pre-treatment with different concentrations of euxanthone. Viability, apoptosis and DNA fragmentation were respectively assessed by CCK-8 assay, Annexin-V/PI staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. The cellular levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were analyzed by enzyme linked immune-sorbent assays (ELISA), and reactive oxygen species (ROS) levels using dichlorodihydrofluorescin diacetate (DCFH) staining. Quantitative RT-PCR and Western blotting were respectively used to analyze the expression levels of specific mRNAs and proteins. HUVECs were transfected with Nrf2 siRNA to induce knockdown of the latter. KEY FINDINGS: Euxanthone pre-treatment rescued the HUVECs from ox-LDL-induced cytotoxicity, apoptosis and DNA fragmentation in a dose-dependent manner. In addition, euxanthone also significantly reversed ox-LDL-triggered loss of mitochondrial membrane potential (MMP), cytochrome C release from mitochondria to cytosol, cleavage of caspase-3 and PARP, and increase in Bax/Bcl-2 ratio. Pre-treatment with euxanthone markedly suppressed ox-LDL-induced ROS generation and inhibition of antioxidant enzymes, as well as the up-regulation of pro-inflammatory factors like MCP-1, IL-1β and TNF-α in the HUVECs. Euxanthone up-regulated and activated Nrf2 by repressing Keap1, and increased the expression of its downstream genes HO-1 and NQO-1. Nrf2 knockdown abrogated the cyto-protective, anti-apoptotic, anti-oxidant and anti-inflammatory effects of euxanthone in ox-LDL-treated HUVECs. Finally, euxanthone activated Nrf2 via the MAPK pathway and blocking the latter likewise negated the protective effects of euxanthone against cell ox-LDL. SIGNIFICANCE: Euxanthone protected HUVECs against the oxidative and inflammatory damage induced by ox-LDL, indicating its potential as a novel therapeutic agent for AS. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/30890405/Cytoprotective_effects_of_euxanthone_against_ox_LDL_induced_endothelial_cell_injury_is_mediated_via_Nrf2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(19)30196-1 DB - PRIME DP - Unbound Medicine ER -