Neuroprotective Effect of Oxysophocarpine by Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen–Glucose Deprivation and Reperfusion

• Published in: Cellular and molecular neurobiology Vol. 38; no. 2; pp. 529 - 540
• Main Authors: Zhao, Peng, Chang, Ren-Yuan, Liu, Ning, Wang, Jing, Zhou, Ru, Qi, Xue, Liu, Yue, Ma, Lin, Niu, Yang, Sun, Tao, Li, Yu-Xiang, He, Yan-Ping, Yu, Jian-Qiang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2018; Springer Nature B.V
• Subjects: Alkaloids - pharmacology; Animals; Animals, Newborn; Biomedical and Life Sciences; Biomedicine; Calcium (intracellular); Calcium (mitochondrial); Cell Biology; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Cells, Cultured; Dose-Response Relationship, Drug; Female; Glucose - deficiency; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; IL-1β; Inflammation; Intracellular; Ischemia; JNK protein; L-Lactate dehydrogenase; Lactic acid; Male; MAP kinase; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Membrane potential; Mitochondria; Neonates; Neurobiology; Neurons; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Neuroprotective Agents - pharmacology; Neurosciences; Original Research; Oxygen; Rats; Rats, Sprague-Dawley; Reperfusion; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; Rodents; Signal transduction; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Hippocampal neurons; Pro-inflammatory mediators; Oxysophocarpine; Oxygen and glucose deprivation
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-017-0501-5

Oxysophocarpine (OSC), an alkaloid isolated from Sophora flavescens Ait, has been traditionally used as a medicinal agent based on the observed pharmacological effects. In this study, the direct effect of OSC against neuronal injuries induced by oxygen and glucose deprivation (OGD) in neonatal rat primary-cultured hippocampal neurons and its mechanisms were investigated. Cultured hippocampal neurons, which were exposed to OGD for 2 h followed by a 24 h reoxygenation, were used as an in vitro model of ischemia and reperfusion. 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to confirm neural damage and to further evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca 2+ ] i and mitochondrial membrane potential (MMP) were measured to determine the intracellular mechanisms and to further estimate the degree of neuronal damage. Changes in expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, p-ERK1/2, p-JNK1/2, and p-p38 MAPK were also observed in the in vitro model. It was shown that OSC (0.8, 2, or 5 µmol/L) significantly attenuated the increased absorbance of MTT, and the release of LDH manifests the neuronal damage by the OGD/R. Meanwhile, the pretreatment of the neurons during the reoxygenation period with OSC significantly increased MMP; it also inhibited [Ca 2+ ] i the elevation in a dose-dependent manner. Furthermore, the pretreatment with OSC (0.8, 2, or 5 µmol/L) significantly down-regulated expressions of IL-1β, TNF-α, p-ERK1/2, p-JNK1/2, and p-p38 MAPK in neonatal rat primary-cultured hippocampal neurons induced by OGD/R injury. In conclusion, OSC displays a protective effect on OGD-injured hippocampal neurons by attenuating expression of inflammatory factors via down-regulated the MAPK signaling pathway.