The plant‐derived alkaloid aloperine prevents ischemia/reperfusion injury‐induced sudden cardiac death

医学 药理学 再灌注损伤 心肌保护 缺血 内科学 心脏病学 钾通道
作者
Zhaoyang Hu,Jiaxue Li,Quanhua Liu,Rían W. Manville,Geoffrey W. Abbott
出处
期刊:The FASEB Journal [Wiley]
卷期号:37 (7) 被引量:5
标识
DOI:10.1096/fj.202300253r
摘要

Sudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from Sophora alopecuroides plants, exhibits antioxidant, anti-inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury-associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion-provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage-gated potassium (Kv) channels were performed using two-electrode voltage clamp analysis of cloned channels expressed in Xenopus laevis oocytes. Aloperine pretreatment (10 mg/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK-MB, α-HBDH, and cTnI post-I/R, and stimulated phosphorylation of ventricular ERK1/2 and STAT-3, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1/2 (with U0126) or STAT-3 (with Ag490) abolished aloperine-induced anti-arrhythmic effects and ERK1/2 and STAT-3 phosphorylation. Interestingly, while aloperine (100 μM) had no effect on cloned Kv4.3 activity, aloperine (1 μM and up) negative-shifted the voltage dependence of hERG activation by ~10 mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti-arrhythmic effects against myocardial ischemia and reperfusion injury-induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1/2/STAT-3 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
桐桐应助杰森斯坦虎采纳,获得10
刚刚
科研通AI2S应助ktx采纳,获得10
刚刚
张羊羔发布了新的文献求助10
2秒前
2秒前
莫凡发布了新的文献求助10
2秒前
morii发布了新的文献求助10
3秒前
ybma发布了新的文献求助30
4秒前
民族风发布了新的文献求助10
6秒前
6秒前
脑洞疼应助DRX采纳,获得10
7秒前
7秒前
8秒前
9秒前
紫陌东门完成签到,获得积分10
10秒前
大模型应助迷路的煎蛋采纳,获得10
10秒前
Hi完成签到,获得积分10
11秒前
feifan123发布了新的文献求助10
11秒前
老迟到的可兰完成签到 ,获得积分10
12秒前
morii发布了新的文献求助10
12秒前
充电宝应助ljie采纳,获得10
12秒前
李健的小迷弟应助吴斯采纳,获得10
12秒前
asdfqwer发布了新的文献求助10
12秒前
13秒前
打打应助冷傲凝琴采纳,获得10
14秒前
14秒前
14秒前
14秒前
笑点低白秋完成签到,获得积分10
14秒前
张羊羔完成签到,获得积分10
15秒前
15秒前
16秒前
照妖镜发布了新的文献求助20
17秒前
搜集达人应助1908采纳,获得10
18秒前
盐茄茄发布了新的文献求助10
19秒前
19秒前
20秒前
清秀寇完成签到,获得积分10
20秒前
柠木完成签到 ,获得积分10
20秒前
21秒前
21秒前
高分求助中
Evolution 3rd edition 1500
保险藏宝图 1000
Lire en communiste 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 700
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 700
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3183068
求助须知:如何正确求助?哪些是违规求助? 2833280
关于积分的说明 7993179
捐赠科研通 2495413
什么是DOI,文献DOI怎么找? 1331490
科研通“疑难数据库(出版商)”最低求助积分说明 636300
邀请新用户注册赠送积分活动 603474