Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKβ/Nrf2/HO-1 Signal Axis.

doi:10.1007/s11064-022-03783-x

科研成果详情

题名	Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKβ/Nrf2/HO-1 Signal Axis.
作者	Shen, Mengya1,2; Zheng, Yuantie2,3; Li, Ge2; Chen, Yinqi1,2; Huang, Lili 2,4; Wu, Jianzhang1,2; Hong, Chenglv5
发表日期	2023-02
发表期刊	Neurochemical research 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Cerebral ischemia–reperfusion injury Heme oxygenase-1 IkappaB kinase beta Nuclear erythroid 2-related factor 2 Oxidative stress
其他关键词	NF-KAPPA-B ; OXIDATIVE STRESS ; ENDOTHELIAL DYSFUNCTION ; IN-VITRO ; 3,4-DIHYDROXYACETOPHENONE ; NRF2 ; INFLAMMATION ; CROSSTALK ; DISCOVERY ; ANALOGS
摘要	Antioxidants represent a potential therapy for cerebral ischemia-reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H2O2)-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKβ) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKβ plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKβ/Nrf2/HO-1 signal axis. Inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI
资助项目	Project of Wenzhou Sci-Tech Bureau[Y20190655];National Natural Science Foundation of China[82003755];Medical Technology Program of Ningbo[2019Y07];Zhejiang Province Natural Science Fund of China[LGF20H310002];
出版者	SPRINGER/PLENUM PUBLISHERS
出版地	NEW YORK
ISSN	0364-3190
EISSN	1573-6903
卷号	48 期号:2 页码:579-590
DOI	10.1007/s11064-022-03783-x
页数	12
WOS类目	Biochemistry & Molecular Biology ; Neurosciences
WOS研究方向	Biochemistry & Molecular Biology ; Neurosciences & Neurology
WOS记录号	WOS:000868372700002
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2022-10
URL	查看原文
PubMed ID	36243818
SCOPUSEID	2-s2.0-85139826090
通讯作者地址	[Wu, Jianzhang]School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China ; [Huang, Lili]Lihuili Hospital Affiliated to Ningbo University,Zhejiang,Ningbo,315100,China ; [Hong, Chenglv]Department of Cardiovascular,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Biochemistry;Cellular and Molecular Neuroscience
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/166914
专题	眼视光学院（生物医学工程学院）、附属眼视光医院药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院附属第一医院_心血管内科
通讯作者	Huang, Lili; Wu, Jianzhang; Hong, Chenglv
作者单位	1.The Eye Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 2.School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 3.The Second Affiliated Hospital,Yuying Children’s Hospital of the Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 4.Lihuili Hospital Affiliated to Ningbo University,Zhejiang,Ningbo,315100,China; 5.Department of Cardiovascular,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
第一作者单位	眼视光学院（生物医学工程学院）、附属眼视光医院; 药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）; 附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	眼视光学院（生物医学工程学院）、附属眼视光医院
推荐引用方式 GB/T 7714	Shen, Mengya,Zheng, Yuantie,Li, Ge,et al. Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKβ/Nrf2/HO-1 Signal Axis.[J]. Neurochemical research,2023,48(2):579-590.
APA	Shen, Mengya., Zheng, Yuantie., Li, Ge., Chen, Yinqi., Huang, Lili., ... & Hong, Chenglv. (2023). Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKβ/Nrf2/HO-1 Signal Axis.. Neurochemical research, 48(2), 579-590.
MLA	Shen, Mengya,et al."Dual Antioxidant DH-217 Mitigated Cerebral Ischemia-Reperfusion Injury by Targeting IKKβ/Nrf2/HO-1 Signal Axis.".Neurochemical research 48.2(2023):579-590.