@article{Wu2026, 
author = {Meizhu Wu and Lingqi Chen and Zhi Guo and Hongshu Liu and Yi Xie and Guosheng Lin and Qiaoyan Zeng and Shilan Chen and Rongji Chen and Yi Huang and Farman Ali and Dawei Lian and Aling Shen and Jun Peng},
title = {Isoliensinine alleviates cardiac apoptosis by activating the PI3K/AKT Pathway: Insights from in Vivo and in Vitro Studies},
year = {2026},
journal = {Food Science and Human Wellness},
keywords = {Hypertension, PI3K/AKT pathway, Cardiac injury, Cardiomyocyte apoptosis, Isoliensinine},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250865},
doi = {10.26599/FSHW.2025.9250865},
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.}
}