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羟基_obtustyrene 可保护神经元细胞免受化学缺氧诱导的细胞死亡。

Hydroxyobtustyrene protects neuronal cells from chemical hypoxia-induced cell death.

机构信息

Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.

Laboratory of Pharmacology, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.

出版信息

J Nat Med. 2018 Sep;72(4):915-921. doi: 10.1007/s11418-018-1224-8. Epub 2018 Jul 9.

Abstract

Hydroxyobtustyrene is a derivative of cinnamyl phenol isolated from Dalbergia odorifera T. Chen. The heartwood, known as 'JiangXiang', is a traditional Chinese medicine. Previous studies showed that hydroxyobtustyrene inhibited the biosynthesis of prostaglandins, which are mediators of neuronal cell death in ischemia. However, it currently remains unclear whether hydroxyobtustyrene protects neurons against ischemic stress. In the present study, we investigated the protective effects of hydroxyobtustyrene against sodium cyanide (NaCN)-induced chemical ischemia. Hippocampal neurons were cultured from the cerebral cortices of E18 Wistar rats. The effects of hydroxyobtustyrene on neuronal survival and trophic effects were estimated under lower and higher cell density conditions. After the treatment of 1 mM NaCN with or without hydroxyobtustyrene, an MTT assay, Hoechst staining, and immunocytochemistry for cyclooxygenase (COX)-2 were performed. Hydroxyobtustyrene increased cell viability under lower, but not normal density conditions. Neither the neurite number nor the length was influenced by hydroxyobtustyrene. NaCN significantly decreased viability and increased fragmentation in cell nuclei, and these changes were prevented by hydroxyobtustyrene. Moreover, NaCN increased the number of COX-2-positive neurons, and this was significantly prevented by the co-treatment with hydroxyobtustyrene. Therefore, hydroxyobtustyrene protected cultured hippocampal neurons against NaCN-induced chemical ischemia, which may be mediated by the inhibition of COX-2 production.

摘要

羟基奥土他汀是从黄檀属香脂中分离出的肉桂基酚衍生物。心材,称为“降香”,是一种传统的中药。先前的研究表明,羟基奥土他汀抑制前列腺素的生物合成,前列腺素是缺血性神经元细胞死亡的介质。然而,目前尚不清楚羟基奥土他汀是否能保护神经元免受缺血应激。在本研究中,我们研究了羟基奥土他汀对氰化钠(NaCN)诱导的化学性缺血的保护作用。将 E18 Wistar 大鼠大脑皮质中的海马神经元进行培养。在较低和较高细胞密度条件下,评估羟基奥土他汀对神经元存活和营养作用的影响。用 1mM NaCN 处理或不处理羟基奥土他汀后,进行 MTT 测定、Hoechst 染色和环氧化酶(COX)-2 的免疫细胞化学染色。羟基奥土他汀在较低密度条件下增加细胞活力,但在正常密度条件下则没有。羟基奥土他汀既不影响神经突的数量,也不影响其长度。NaCN 显著降低细胞活力并增加细胞核碎片,而羟基奥土他汀则能预防这些变化。此外,NaCN 增加了 COX-2 阳性神经元的数量,而羟基奥土他汀的共同处理则显著阻止了这一现象。因此,羟基奥土他汀能保护培养的海马神经元免受 NaCN 诱导的化学性缺血,这可能是通过抑制 COX-2 的产生来介导的。

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