Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.
Eur J Pharmacol. 2024 May 5;970:176465. doi: 10.1016/j.ejphar.2024.176465. Epub 2024 Mar 11.
Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects.
Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium.
This study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 μg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups.
On the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin.
Arglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose.
Arglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.
ArgLabin 是一种植物生物碱（倍半萜内酯），可用作抗癌药物。它具有潜在的抗糖尿病和抗动脉粥样硬化作用。
ArgLabin 作为多种疾病的抗炎药物具有治疗作用，因此引起了特别关注。由于 ArgLabin 抑制表皮生长因子受体（EGFR）酪氨酸激酶，因此对其产生心脏毒性的担忧是合理的。本研究旨在探讨 ArgLabin 对心肌的保护作用。
本研究旨在评估 ArgLabin 在大鼠心肌坏死实验模型中对心肌的影响。在异丙肾上腺素（ISO）诱导的心肌坏死模型组和自身组中，研究了不同剂量的 ArgLabin（2.5、5 和 10μg/kg）作为预处理 21 天的效果。
第 22 天，进行血流动力学、组织病理学、电子显微镜、氧化应激标志物、炎症介质、凋亡标志物、炎症小体介质和 Western blot 分析，以评估 ArgLabin 的作用。
ArgLabin 预处理可改善低剂量异丙肾上腺素诱导的大鼠心肌坏死模型中的血流动力学参数和组织病理学发现。ArgLabin 的给药改变了心肌结构，并通过激活 NFκB/MAPK 通路调节心肌功能，导致心肌损伤，随着剂量的增加而加剧。
ArgLabin 通过依赖炎症小体的途径发挥部分心脏保护作用，并通过非依赖炎症小体的途径介导损伤。
