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Improvement of cerebral ischemia/reperfusion injury by daucosterol palmitate-induced neuronal apoptosis inhibition via PI3K/Akt/mTOR signaling pathway.
Metabolic Brain Disease ( IF 3.6 ) Pub Date : 2020-05-04 , DOI: 10.1007/s11011-020-00575-6
Huiyuan Zhang 1 , Yamin Song 1 , Cong Feng 2
Affiliation  

Traditional Chinese medicine has growing importance in the treatment of ischemia stroke due to its abundance and low drug resistance. In this study, we aim to investigate the therapeutic potential of daucosterol palmitate against ischemia stroke, as well as its neuro-protective mechanism. The dose-response effects of daucosterol palmitate in the protection from brain damage were evaluated in a cerebral ischemia/reperfusion (I/R) rat model. The correlation of neuro-protective effects of daucosterol palmitate with apoptosis inhibition was examined and the possible signaling targets were identified. Our findings revealed that daucosterol palmitate treatment after 2 h' ischemia significantly lowered brain damage, and neuronal cell apoptosis caused by I/R injury in a dose-response mode (20, 40 and 80 mg/kg). Western blot analysis indicated that daucosterol palmitate could reverse the effects of I/R injury on protein expression of PI3K and mTOR, and phosphorylation of Akt. Contrarily, inactivation of PI3K using wortmannin dramatically antagonized the effect of daucosterol palmitate for I/R injury. With these findings, it supports the application potential of daucosterol palmitate in the treatment of ischemia stroke. Besides, the PI3K/Akt/mTOR pathway might be potential cellular targets for daucosterol palmitate.

中文翻译:

棕榈甾醇棕榈酸酯通过PI3K/Akt/mTOR信号通路抑制神经元凋亡改善脑缺血/再灌注损伤。

中医药因其丰富且耐药性低而在缺血性脑卒中的治疗中越来越重要。在这项研究中,我们旨在研究豆蔻甾醇棕榈酸酯对缺血性中风的治疗潜力及其神经保护机制。在脑缺血/再灌注 (I/R) 大鼠模型中评估了棕榈甾醇棕榈酸酯在防止脑损伤方面的剂量反应效应。检查了棕榈甾醇棕榈酸酯的神经保护作用与细胞凋亡抑制的相关性,并确定了可能的信号靶点。我们的研究结果表明,缺血2小时后的棕榈甾醇棕榈酸酯治疗显着降低了脑损伤,以及以剂量反应模式(20、40和80 mg / kg)I / R损伤引起的神经元细胞凋亡。Western blot分析表明,棕榈甾醇棕榈酸酯可以逆转I/R损伤对PI3K和mTOR蛋白表达以及Akt磷酸化的影响。相反,使用渥曼青霉素使 PI3K 失活显着拮抗了棕榈甾醇棕榈酸酯对 I/R 损伤的作用。有了这些发现,它支持了豆蔻甾醇棕榈酸酯在治疗缺血性中风中的应用潜力。此外,PI3K / Akt / mTOR 通路可能是豆蔻甾醇棕榈酸酯的潜在细胞靶点。它支持了豆蔻甾醇棕榈酸酯在治疗缺血性中风中的应用潜力。此外,PI3K / Akt / mTOR 通路可能是豆蔻甾醇棕榈酸酯的潜在细胞靶点。它支持了豆蔻甾醇棕榈酸酯在治疗缺血性中风中的应用潜力。此外,PI3K / Akt / mTOR 通路可能是豆蔻甾醇棕榈酸酯的潜在细胞靶点。
更新日期:2020-05-04
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