KEAP1 inhibitor-scutellarin-based liposomes serve as an antioxidant switch foroxidative stress induced by ischemic stroke injury  

作　　者：Kai-Rui Liu Jun-Li Ba Yun Wang Sheng-Tao Hu Lu Gao Xiao-Ning Gao Chang-Hua Kou Jun Kang 

机构地区：[1]School of Life Sciences,Faculty of Medicine,Tianjin University,Tianjin 300072,China [2]Hepatobiliary Pancreatic Center,Xuzhou Central Hospital,Xuzhou 221009,China [3]School of Basic Medical Science,Beijing Health Vocational College,Beijing 102402,China

出　　处：《Traditional Medicine Research》2025年第4期11-20,共10页TMR传统医学研究

基　　金：Medical andHealth Project (2023, No. KC23178).

摘　　要：Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.

关 键 词：oxidative stress SCUTELLARIN liposomes KEAP1 NRF2 

分 类 号：R74[医药卫生—神经病学与精神病学]