Voacangine protects hippocampal neuronal cells against oxygen–glucose deprivation/reoxygenation-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling

IF 2.7 4区医学 Q3 TOXICOLOGY

Journal of Applied Toxicology Pub Date : 2024-04-26 DOI:10.1002/jat.4615

Ying Li, Yan Sun, Jianghong Wang, Xiaolong Wang, Wenjie Yang

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引用次数: 0

Abstract

Voacangine, a naturally occurring alkaloid, has been testified to display beneficial effects on a variety of human diseases, but its role in ischemic stroke is unclear. The impacts of voacangine on oxygen–glucose deprivation/reoxygenation (OGD/R)-tempted hippocampal neuronal cells are investigated. The bioinformatics analysis found that voacangine is a bioactive ingredient that may have good effects on ischemic stroke. KEGG pathways analysis found that voacangine may regulate ischemic stroke through modulating the PI3K-Akt-FoxO signaling pathway. Voacangine could mitigate OGD/R-tempted cytotoxicity in HT22 cells. Voacangine mitigated OGD/R-tempted oxidative stress in HT22 cells by diminishing reactive oxygen species level and enhancing superoxide dismutase level. Voacangine mitigated OGD/R-tempted ferroptosis in HT22 cells. Voacangine promoted activation of the PI3K-Akt-FoxO signaling in OGD/R-induced HT22 cells. Inactivation of the PI3K-Akt-FoxO signaling pathway reversed the protective effects of voacangine against OGD/R-tempted oxidative stress, cytotoxicity, and ferroptosis in HT22 cells. In conclusion, voacangine protects hippocampal neuronal cells against OGD/R-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling.

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伏安康定通过激活PI3K-Akt-FoxO信号传导，保护海马神经元细胞免受氧-葡萄糖剥夺/复氧引起的氧化应激和铁变态反应的影响。

沃卡因是一种天然生物碱，已被证实对多种人类疾病有益处，但它在缺血性中风中的作用尚不清楚。本研究探讨了voacangine对缺氧-葡萄糖剥夺/复氧（OGD/R）诱导的海马神经元细胞的影响。生物信息学分析发现，voacangine 是一种生物活性成分，可能对缺血性中风有良好的疗效。KEGG通路分析发现，voacangine可通过调节PI3K-Akt-FoxO信号通路来调节缺血性中风。Voacangine能减轻OGD/R诱导的HT22细胞毒性。通过降低活性氧水平和提高超氧化物歧化酶水平，Voacangine减轻了OGD/R诱导的HT22细胞氧化应激。Voacangine可减轻HT22细胞中OGD/R诱导的铁变态反应。Voacangine 促进了 OGD/R 诱导的 HT22 细胞中 PI3K-Akt-FoxO 信号的激活。PI3K-Akt-FoxO信号通路的失活逆转了沃卡金碱对OGD/R诱导的HT22细胞氧化应激、细胞毒性和铁细胞沉降的保护作用。总之，奥卡因通过激活PI3K-Akt-FoxO信号通路，保护海马神经元细胞免受OGD/R引起的氧化应激和铁中毒的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Applied Toxicology 医学-毒理学

CiteScore

7.00

自引率

6.10%

发文量

145

审稿时长

1 months

期刊介绍： Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.