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
刚刚
刚刚
嗯哼应助TK采纳,获得20
1秒前
yoowt发布了新的文献求助10
2秒前
南音发布了新的文献求助10
3秒前
lily完成签到,获得积分10
4秒前
6秒前
苏卿应助邹修坤采纳,获得10
6秒前
活泼酸奶完成签到,获得积分10
6秒前
6秒前
冯哒哒发布了新的文献求助10
6秒前
6秒前
科研通AI2S应助cc采纳,获得10
7秒前
FashionBoy应助Lu采纳,获得10
7秒前
隐形曼青应助aa采纳,获得10
7秒前
LALALA卫卫J完成签到,获得积分10
8秒前
泽鑫完成签到,获得积分10
8秒前
魔法签证1993完成签到,获得积分10
8秒前
共享精神应助乔心采纳,获得10
9秒前
小脑袋完成签到,获得积分10
11秒前
11秒前
TK完成签到,获得积分10
11秒前
Cwx2020发布了新的文献求助10
12秒前
杨然发布了新的文献求助10
12秒前
COIN_77完成签到,获得积分10
12秒前
16秒前
展信佳完成签到,获得积分10
16秒前
17秒前
17秒前
18秒前
张涛发布了新的文献求助10
20秒前
21秒前
Lu发布了新的文献求助10
23秒前
丘比特应助sybil采纳,获得10
23秒前
展信佳发布了新的文献求助10
26秒前
生活的狗完成签到,获得积分10
26秒前
CooL完成签到 ,获得积分10
27秒前
28秒前
29秒前
酷波er应助语霖仙采纳,获得10
29秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
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
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 3185915
求助须知:如何正确求助?哪些是违规求助? 2836227
关于积分的说明 8008323
捐赠科研通 2498654
什么是DOI,文献DOI怎么找? 1333703
科研通“疑难数据库(出版商)”最低求助积分说明 636907
邀请新用户注册赠送积分活动 604738