ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1600435
This article is part of the Research TopicMechanisms and Novel Therapeutic Targets and Approaches for Mitochondrial Dysfunction in Neurological and Cardiovascular DiseasesView all 6 articles
Gypenoside XLIX inhibiting PI3K/AKT/FOXO1 signaling pathway mediated neuronal mitochondrial autophagy to improve patients with ischemic stroke
Provisionally accepted
Yonglei Liu1
Hongdie Mao2Zhengguang Sha2Jishuai Zhao2Hui Cai2Rong Xi2Zhenzhu Zhao2Xiaoling Yin2Lin Yang2Changyun Liu1*- 1Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- 2The First Affiliated Hospital of Dali University, Dali, Yunnan, China
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Stroke remains a leading cause of mortality and disability worldwide, with limited treatment options highlighting the need for alternative therapies. Mitochondrial autophagy plays a crucial role in stroke pathology, presenting a potential therapeutic target. Gypenoside XLIX demonstrated mitochondrial protective effects. However, its efficacy in preventing mitochondrial damage in neuronal cells remained unclear. Therefore, this study investigated the role and mechanism of Gypenoside XLIX in alleviating ischemic stroke injury. We evaluated the neuroprotective effects of Gypenoside XLIX using cellular oxygen-glucose deprivation (OGD) and middle cerebral artery occlusion (MCAO) rat models. The bioinformatic analyses revealed that Gypenoside XLIX interacts with the PI3K-Akt signaling pathway. In OGD cells, Gypenoside XLIX facilitated autophagic flux and reduces apoptosis and reactive oxygen species (ROS) levels. Additionally, Gypenoside XLIX upregulated p-PI3K and p-AKT while downregulating FOXO1 protein expression. In MCAO rats, Gypenoside XLIX markedly decreased the infarct size, brain edema rate, and cell apoptosis, while enhancing mitochondrial membrane potential, oxidative stress indicators (SOD, GSH-Px, and CAT), and autophagic flux. These results suggest that Gypenoside XLIX might alleviate ischemic stroke injury by activating the PI3K/AKT/FOXO1 pathway, which in turn promotes mitochondrial autophagy and reduces neuronal apoptosis.
Keywords: ischemic stroke, gypenoside XLIX, Mitochondrial autophagy, FoxO1, PI3K/AKT
Received: 26 Mar 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Liu, Mao, Sha, Zhao, Cai, Xi, Zhao, Yin, Yang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Changyun Liu, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China
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