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希考苷 A 可通过抑制氧化应激和激活 Nrf2 保护 PC12 细胞免受 OGD/R 损伤。

Sikokianin A from protects PC12 cells against OGD/R-induced injury via inhibiting oxidative stress and activating Nrf2.

机构信息

School of Pharmacy and Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University , Xuzhou , China.

Physical Education College, Jilin Sport University , Changchun , China.

出版信息

Nat Prod Res. 2019 Dec;33(23):3450-3453. doi: 10.1080/14786419.2018.1480019. Epub 2018 May 28.

Abstract

Ischemic cerebral stroke is a severe cause of human death and disability. Natural products play an important role in the discovery of novel therapy for cerebral ischemia. Herein, we investigate the neuroprotective effects of sikokianin A identifiedfrom using PC12 cell exposed to OGD/R. The results revealed sikokianin A can improve the poor viability and release of intracellular LDH in PC12 cells induced by OGD/R. Further studies have demonstrated the increased ROS and MDA together with reduced SOD activity were attenuated by sikokianin A. Meanwhile, decreased mitochondrial membrane potential, activated Caspase-3, down-regulated Bcl-2 and up-regulated Bax were reversed. These results indicate the protective effects of sikokianin A are associated with inhibiting oxidative stress and apoptosis resulting from OGD/R. Additionally, sikokianin A can activate Nrf2 and downstream HO-1 in PC12 cells treated by OGD/R, which implied Nrf2/HO-1 signaling pathway was involved in the protective effects of sikokianin A.

摘要

缺血性脑卒中是导致人类死亡和残疾的严重原因。天然产物在发现治疗脑缺血的新疗法方面发挥着重要作用。本文从 中鉴定出的石杉堿甲素,研究了其对 OGD/R 诱导的 PC12 细胞的神经保护作用。结果表明,石杉堿甲素可以改善 OGD/R 诱导的 PC12 细胞活力下降和细胞内 LDH 的释放。进一步的研究表明,石杉堿甲素可以减轻 OGD/R 引起的 ROS 和 MDA 增加以及 SOD 活性降低。同时,线粒体膜电位降低、Caspase-3 激活、Bcl-2 下调和 Bax 上调也得到了逆转。这些结果表明,石杉堿甲素的保护作用与抑制 OGD/R 引起的氧化应激和细胞凋亡有关。此外,石杉堿甲素可以激活 OGD/R 处理的 PC12 细胞中的 Nrf2 和下游的 HO-1,这表明 Nrf2/HO-1 信号通路参与了石杉堿甲素的保护作用。

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