Nobiletin alleviates myocardial ischemia-reperfusion injury via ferroptosis in rats with type-2 diabetes mellitus

作者全名："Huang, Qin; Tian, Liqun; Zhang, Yi; Qiu, Zhen; Lei, Shaoqing; Xia, Zhong-Yuan"

作者地址："[Huang, Qin; Tian, Liqun; Zhang, Yi; Qiu, Zhen; Lei, Shaoqing; Xia, Zhong-Yuan] Wuhan Univ, Renmin Hosp, Dept Anaesthesiol, Wuhan 430060, Hubei, Peoples R China; [Tian, Liqun] Chongqing Med Univ, Affiliated Hosp 1, Dept Anaesthesiol, Chongqing, Peoples R China; [Zhang, Yi] Shandong First Med Univ, Affiliated Hosp 1, Dept Anaesthesiol, Jinan, Peoples R China; [Zhang, Yi] Shandong Prov Qianfoshan Hosp, Shandong Inst Anesthesia & Resoiratory Crit Med, Jinan, Peoples R China"

通信作者："Xia, ZY (通讯作者)，Wuhan Univ, Renmin Hosp, Dept Anaesthesiol, Wuhan 430060, Hubei, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000997614600001

JCR分区：Q1

影响因子：7.5

年份：2023

卷号：163

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Ferroptosis; Myocardial ischemia-reperfusion injury; Nobiletin; Susceptibility; Type-2 diabetes

摘要："Susceptibility to myocardial ischemia-reperfusion (IR) injury in type-2 diabetes (T2DM) remains disputed, although studies have reported that ferroptosis is associated with myocardial IR injury. Nobiletin, a flavonoid isolated from citrus peels, is an antioxidant that possesses anti-inflammatory and anti-diabetic activities. How-ever, it remains unknown whether nobiletin has any protective effects on susceptibility to myocardial IR injury during T2DM in rats via ferroptosis. To investigate the effects and underlying mechanisms of nobiletin on myocardial IR injury during T2DM, we induced myocardial IR model in rats at T2DM onset vs mature disease. We also established a high-fat high-glucose (HFHG) and hypoxia-reoxygenation (H/R) model in H9c2 cells to imitate abnormal glycolipid metabolism during T2DM. Myocardial injury, oxidative stress and ferroptosis towards myocardial IR in rats with mature T2DM but not at T2DM onset were increased. These changes were restored under treatment with ferrostain-1 or nobiletin. Both ferrostain-1 and nobiletin decreased the expression of ferroptosis-related proteins including Acyl-CoA synthetase long chain family member 4 (ACSL4) and nuclear receptor coactivator 4 (NCOA4) but not glutathione peroxidase 4 (GPX4) in rats with mature T2DM and cells with HFHG and H/R injury. Nobiletin strengthened the effect of si-ACSL4 on inhibiting ACSL4 expression, and also inhibited the effect of Erastin or oe-ACSL4 on increasing ACSL4 expression. Taken together, our data in-dicates that ferroptosis involves in susceptibility to myocardial IR injury in rats during T2DM. Nobiletin has therapeutic potential for alleviating myocardial IR injury associated with ACSL4-and NCOA4-related ferroptosis."

基金机构：National Natural Science Foundation of China [81970722]

基金资助正文："Funding This work was supported by the National Natural Science Foundation of China [grant number: 81970722] . The organization s had no role in study design, data collection and analysis, data interpretation, decision to publish or in the preparation of the manuscript."