亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

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
杨枝甘露完成签到,获得积分20
4秒前
醒醒完成签到,获得积分10
12秒前
鳗鱼邪欢完成签到 ,获得积分10
34秒前
追三完成签到 ,获得积分10
36秒前
57秒前
JamesPei应助羊咩咩采纳,获得10
1分钟前
hehe_733完成签到,获得积分10
1分钟前
1分钟前
1分钟前
羊咩咩发布了新的文献求助10
1分钟前
沉默鼠鼠发布了新的文献求助10
1分钟前
羊咩咩完成签到,获得积分10
1分钟前
1分钟前
1分钟前
超级裁缝发布了新的文献求助10
1分钟前
超级裁缝完成签到,获得积分10
1分钟前
1分钟前
pysa发布了新的文献求助10
1分钟前
2分钟前
pysa完成签到,获得积分10
2分钟前
z123完成签到,获得积分10
2分钟前
脑洞疼应助dahai采纳,获得10
2分钟前
北雨完成签到,获得积分10
2分钟前
搜集达人应助科研通管家采纳,获得10
3分钟前
4分钟前
dahai发布了新的文献求助10
4分钟前
苏晓聪完成签到,获得积分10
4分钟前
4分钟前
嗨嗨嗨完成签到 ,获得积分10
4分钟前
dahai完成签到,获得积分10
4分钟前
重要冲发布了新的文献求助10
4分钟前
4分钟前
嗯哼举报小春求助涉嫌违规
4分钟前
4分钟前
大个应助科研通管家采纳,获得10
5分钟前
5分钟前
eth完成签到 ,获得积分10
5分钟前
6分钟前
6分钟前
jun完成签到 ,获得积分10
6分钟前
高分求助中
Spray / Wall-interaction Modelling by Dimensionless Data Analysis 2000
Aspects of Babylonian celestial divination: the lunar eclipse tablets of Enūma Anu Enlil 500
Mathematics and Finite Element Discretizations of Incompressible Navier—Stokes Flows 500
Dictionary of socialism 350
Mixed-anion Compounds 300
Geochemistry, 2nd Edition 地球化学经典教科书第二版 300
Idoxuridine 260
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 3196756
求助须知:如何正确求助?哪些是违规求助? 2845422
关于积分的说明 8054088
捐赠科研通 2510046
什么是DOI,文献DOI怎么找? 1342199
科研通“疑难数据库(出版商)”最低求助积分说明 639340
邀请新用户注册赠送积分活动 608633