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
1秒前
lijall完成签到,获得积分10
2秒前
2秒前
圈儿完成签到,获得积分10
3秒前
3秒前
不配.应助nig采纳,获得10
5秒前
烤地瓜要吃甜完成签到,获得积分10
5秒前
joyce完成签到,获得积分10
6秒前
威武语儿发布了新的文献求助10
6秒前
ringo完成签到,获得积分10
7秒前
wxxx完成签到,获得积分10
7秒前
8秒前
ww完成签到,获得积分10
8秒前
亭语完成签到 ,获得积分0
9秒前
大力的含卉完成签到,获得积分10
9秒前
赘婿应助书生采纳,获得10
9秒前
饱满的大碗完成签到 ,获得积分10
11秒前
Kirin完成签到,获得积分10
11秒前
华仔应助江上清风游采纳,获得10
12秒前
13秒前
13秒前
bkagyin应助dd采纳,获得10
15秒前
Echo完成签到,获得积分10
15秒前
ding应助longyu915采纳,获得80
15秒前
16秒前
笑点低的云朵完成签到,获得积分10
16秒前
16秒前
16秒前
16秒前
17秒前
路漫漫123完成签到,获得积分10
17秒前
17秒前
Kirin发布了新的文献求助10
17秒前
局内人发布了新的文献求助10
17秒前
19秒前
19秒前
YZT8848发布了新的文献求助100
19秒前
一一完成签到,获得积分10
19秒前
ln完成签到,获得积分10
19秒前
Echo发布了新的文献求助200
20秒前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
Write Like a Chemist: A Guide and Resource (第二版) 600
Mixed-anion Compounds 600
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
Earth System Geophysics 500
Aspects of Babylonian celestial divination: the lunar eclipse tablets of Enūma Anu Enlil 500
Geochemistry, 2nd Edition 地球化学经典教科书第二版 401
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 3199867
求助须知:如何正确求助?哪些是违规求助? 2849321
关于积分的说明 8069162
捐赠科研通 2513353
什么是DOI,文献DOI怎么找? 1346191
科研通“疑难数据库(出版商)”最低求助积分说明 640184
邀请新用户注册赠送积分活动 610035