Astragaloside IV promotes neuronal axon regeneration by inhibiting the PTEN/AKT pathway

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-01-08 DOI:10.1016/j.brainres.2025.149451

Luning Lin , Chenyang Zhao , Huijuan Lv , Liangrong Zhu , Wangen Wang , Xintian Zheng

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Abstract

Background

Neuronal survival and regeneration are critical aspects of recovery from ischemic brain injuries. Astragaloside IV (AS-IV), a saponin extracted from the traditional Chinese medicine Astragalus membranaceus, has shown promise in promoting neuronal health. This study investigates the effects of AS-IV on neuronal survival and apoptosis post-oxygen-glucose deprivation (OGD), focusing on the modulation of the PTEN/AKT signaling pathway.

Methods

Rat primary neuronal cells were isolated and subjected to OGD to simulate ischemic conditions. Afterwards, cells were treated with low and high doses of AS-IV. Neuronal viability and apoptosis were assessed using MTT and flow cytometry (FCM) assays. Immunofluorescence and Western blot analyses were performed to evaluate the expression of neuronal markers and proteins involved in the PTEN/AKT pathway.

Results

Post-OGD, neuronal cells exhibited decreased viability and increased apoptosis, which were significantly mitigated by AS-IV. Immunofluorescence showed enhanced Tuj1 expression, indicating increased neuronal purity and survival, enhanced NF200 expression, indicating increased axon lengths. FCM results revealed reduced apoptosis rates, particularly with higher doses of AS-IV. Western blot analysis confirmed inhibition of PTEN and activation of AKT, facilitating enhanced neuronal survival and axona regeneration. Additionally, overexpression of PTEN negated the anti-apoptotic effects of AS-IV, underscoring the critical role of the PTEN/AKT pathway in AS-IV mediated neuroprotection.

Conclusion

AS-IV enhances neuronal survival and axona regeneration by modulating the PTEN/AKT pathway, highlighting its potential as a therapeutic agent for ischemic brain injuries. These findings suggest that targeting this pathway could be a strategic focus for developing effective neuroprotective therapies.

Abstract Image

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黄芪甲苷通过抑制PTEN/AKT通路促进神经元轴突再生。

背景：神经元的存活和再生是缺血性脑损伤恢复的关键方面。黄芪甲苷（Astragaloside IV, AS-IV）是一种从中药黄芪中提取的皂苷，具有促进神经细胞健康的作用。本研究探讨AS-IV对氧葡萄糖剥夺（OGD）后神经元存活和凋亡的影响，重点研究其对PTEN/AKT信号通路的调节作用。方法：分离大鼠原代神经细胞，进行OGD模拟缺血状态。然后，用低剂量和高剂量的AS-IV处理细胞。采用MTT和流式细胞术（FCM）检测神经元活力和凋亡。采用免疫荧光和Western blot分析评估PTEN/AKT通路相关神经元标志物和蛋白的表达。结果：ogd后，神经元细胞活力下降，细胞凋亡增加，AS-IV显著缓解。免疫荧光显示Tuj1表达增强，表明神经元纯度和存活率增加；NF200表达增强，表明轴突长度增加。FCM结果显示凋亡率降低，特别是高剂量AS-IV。Western blot分析证实了PTEN的抑制和AKT的激活，促进了神经元存活和轴突再生。此外，PTEN过表达可抑制AS-IV的抗凋亡作用，这表明PTEN/AKT通路在AS-IV介导的神经保护中起着关键作用。结论：as - iv通过调节PTEN/AKT通路增强神经元存活和轴突再生，提示其作为缺血性脑损伤治疗药物的潜力。这些发现表明，靶向这一途径可能是开发有效神经保护疗法的战略重点。

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

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.