Asiatic acid alleviates subarachnoid hemorrhage-induced brain injury in rats by inhibiting ferroptosis of neurons via targeting acyl-coenzyme a oxidase 1.

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-11-03 DOI:10.1016/j.neuropharm.2024.110208
Yukun Hu, Jingyu Gu, Xin Jin, Xiaoxiao Wu, Haiying Li, Lei Bai, Jiang Wu, Xiang Li
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Abstract

The occurrence of subarachnoid hemorrhage (SAH) can lead to brain injury, which is a fatal condition with limited effective clinical intervention strategies. The naturally occurring component Asiatic acid (AA), found in the tropical plant Centella asiatica, has been reported to possess neuroprotective properties. The objective of this study was to evaluate the neuroprotective effect of AA following SAH and investigate its potential mechanisms. The SAH model was established in male Sprague-Dawley (SD) rats through intravascular perforation, following a standardized protocol. The administration of AA was performed via gavage following SAH. A lentiviral vector was constructed and utilized for the knockdown of Acyl Coenzyme A Oxidase 1 (ACOX1) Firstly, AA treatment effectively improves brain neurological deficit, neuronal damage, and iron deposition induced by SAH. Furthermore, it has been demonstrated that AA directly interacts with ACOX1, which exhibits decreased expression in neurons following SAH. Additionally, our study reveals AA can reverse SAH-induced reduction in ACOX1 expression, concurrently ameliorating neuronal ferroptosis. This improvement is evidenced by reduced lipid peroxidation, including mitigated GSH depletion, decreased MDA production, and increased GPX4 content and activity. Also, AA enhances mitochondrial constriction while alleviating cristae disruption induced by SAH, providing crucial insights into its neuroprotective effects against neuronal ferroptosis in SAH. Moreover, when ACOX1 is knocked down, the neuroprotective effects of AA are weakened. Collectively, this study elucidated the neuroprotective effect of AA by inhibiting neuronal cell ferroptosis through targeting ACOX1. These findings suggest that AA holds promise as a potential therapeutic candidate for ameliorating SAH-induced brain injury.

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积雪草酸通过靶向酰辅酶A氧化酶1抑制神经元的铁凋亡,从而减轻蛛网膜下腔出血诱发的大鼠脑损伤。
蛛网膜下腔出血(SAH)可导致脑损伤,是一种致命的疾病,但有效的临床干预策略有限。据报道,热带植物积雪草中的天然成分积雪草酸(AA)具有神经保护作用。本研究的目的是评估 AA 在 SAH 后的神经保护作用并研究其潜在机制。按照标准化方案,通过血管内穿孔在雄性 Sprague-Dawley (SD) 大鼠中建立 SAH 模型。SAH 后通过灌胃给予 AA。首先,AA 能有效改善 SAH 引起的脑神经功能缺损、神经元损伤和铁沉积。此外,有研究表明 AA 可直接与 ACOX1 相互作用,而 ACOX1 在 SAH 后的神经元中表达减少。此外,我们的研究发现 AA 可以逆转 SAH 引起的 ACOX1 表达减少,同时改善神经元的铁沉积。这种改善体现在脂质过氧化的减少,包括 GSH 消耗的减轻、MDA 生成的减少以及 GPX4 含量和活性的增加。此外,AA 还能增强线粒体收缩,同时减轻 SAH 引起的嵴破坏,这为其在 SAH 中防止神经元铁骤变的神经保护作用提供了重要的启示。此外,当 ACOX1 被敲除时,AA 的神经保护作用会减弱。总之,本研究阐明了 AA 通过靶向 ACOX1 抑制神经元细胞铁嗜性的神经保护作用。这些发现表明,AA有望成为改善SAH诱导的脑损伤的潜在候选疗法。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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