Isoliensinine alleviates cardiac apoptosis by activating the PI3K/AKT Pathway: Insights from in Vivo and in Vitro Studies

IF 7.3 1区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY

Food Science and Human Wellness Pub Date : 2026-01-01 DOI:10.26599/fshw.2025.9250865

Meizhu Wu, Lingqi Chen, Zhi Guo, Hongshu Liu, Yi Xie, Guosheng Lin, Qiaoyan Zeng, Shilan Chen, Rongji Chen, Yi Huang, Farman Ali, Dawei Lian, Aling Shen, Jun Peng

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Abstract

This study investigated the cardioprotective effects of Isoliensinine, a bisbenzylisoquinoline alkaloid from Nelumbo nucifera Gaertn, and its underlying mechanisms. Spontaneous hypertensive rats (SHR) received Isoliensinine (2.5, 5, 10 mg/kg/day) or valsartan (10 mg/kg/day) for 10 weeks, with Wistar-Kyoto rats as controls. Cardiac function, histopathology, apoptosis, and transcriptomic changes were evaluated in vivo and in Angtension II (AngII)-stimulated H9c2 cardiomyocytes in vitro. Isoliensinine significantly improved left ventricular function, and ameliorated pathological cardiac damage in SHR. Transcriptomic analysis revealed that Isoliensinine reversed 111 up-regulated and 127 down-regulated transcripts in cardiac tissues of SHR, with enrichment of pathways related to apoptosis and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Both in vivo and in vitro experiments confirmed that Isoliensinine reduced cardiomyocyte apoptosis and restored PI3K/AKT phosphorylation. Cellular thermal shift assay (CETSA) and molecular docking supported potential binding of Isoliensinine to PI3K and AKT. Co-treatment with PI3K/AKT activator 740Y-P did not negate the effects of Isoliensinine, suggesting pathway specificity. These findings indicated that Isoliensinine alleviates hypertensive cardiac dysfunction by inhibiting cardiomyocyte apoptosis primarily through modulation of the PI3K/AKT pathway and may serve as a promising therapeutic agent for hypertension.

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异连体肌氨酸通过激活PI3K/AKT通路减轻心脏凋亡：来自体内和体外研究的见解

本研究探讨了莲子双苄基异喹啉生物碱异连体碱的心脏保护作用及其机制。自发性高血压大鼠（SHR）接受异连体碱（2.5、5、10 mg/kg/天）或缬沙坦（10 mg/kg/天）治疗10周，Wistar-Kyoto大鼠为对照。在体内和体外Angtension II （AngII）刺激的H9c2心肌细胞中评估心功能、组织病理学、细胞凋亡和转录组学变化。异连肌氨酸可显著改善SHR患者的左心室功能，改善病理性心脏损伤。转录组学分析显示，异连体氨酸逆转了SHR心脏组织中111个上调转录本和127个下调转录本，并富集了凋亡相关通路和磷酸肌肽3激酶(PI3K)/蛋白激酶B （AKT）信号通路。体内和体外实验均证实异连肠氨酸可减少心肌细胞凋亡，恢复PI3K/AKT磷酸化。细胞热移实验（CETSA）和分子对接支持异连体氨酸与PI3K和AKT的潜在结合。与PI3K/AKT激活剂740Y-P联合治疗并没有否定异连体氨酸的作用，这表明了途径的特异性。这些发现表明，异连体氨酸主要通过调节PI3K/AKT通路抑制心肌细胞凋亡，从而减轻高血压心功能障碍，可能是一种有前景的高血压治疗剂。

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来源期刊

Food Science and Human Wellness Agricultural and Biological Sciences-Food Science

CiteScore

8.30

自引率

5.70%

发文量

审稿时长

28 days

期刊介绍： Food Science and Human Wellness is an international peer-reviewed journal that provides a forum for the dissemination of the latest scientific results in food science, nutriology, immunology and cross-field research. Articles must present information that is novel, has high impact and interest, and is of high scientific quality. By their effort, it has been developed to promote the public awareness on diet, advocate healthy diet, reduce the harm caused by unreasonable dietary habit, and directs healthy food development for food industrial producers.