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Neuroprotective Effect of Oxysophocarpine by Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion.
Cell Mol Neurobiol. 2018 Mar; 38(2):529-540.CM

Abstract

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 [Ca2+]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 [Ca2+]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.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China. Pharmacy Department of Yulin First Hospital, Shaanxi, China.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China.Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China.Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China.Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China.College of Nursing, Ningxia Medical University, Yinchuan, China.General Hospital of Ningxia Medical University, 804 Shengli Street, Yinchuan, 750004, China. heyanping_1982@163.com.Department of Pharmacology, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China. yujq910315@163.com. Ningxia Hui Medicine Modern Engineering Research Center, Ningxia Medical University, Yinchuan, China. yujq910315@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28488010

Citation

Zhao, Peng, et al. "Neuroprotective Effect of Oxysophocarpine By Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion." Cellular and Molecular Neurobiology, vol. 38, no. 2, 2018, pp. 529-540.
Zhao P, Chang RY, Liu N, et al. Neuroprotective Effect of Oxysophocarpine by Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion. Cell Mol Neurobiol. 2018;38(2):529-540.
Zhao, P., Chang, R. Y., Liu, N., Wang, J., Zhou, R., Qi, X., Liu, Y., Ma, L., Niu, Y., Sun, T., Li, Y. X., He, Y. P., & Yu, J. Q. (2018). Neuroprotective Effect of Oxysophocarpine by Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion. Cellular and Molecular Neurobiology, 38(2), 529-540. https://doi.org/10.1007/s10571-017-0501-5
Zhao P, et al. Neuroprotective Effect of Oxysophocarpine By Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion. Cell Mol Neurobiol. 2018;38(2):529-540. PubMed PMID: 28488010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective Effect of Oxysophocarpine by Modulation of MAPK Pathway in Rat Hippocampal Neurons Subject to Oxygen-Glucose Deprivation and Reperfusion. AU - Zhao,Peng, AU - Chang,Ren-Yuan, AU - Liu,Ning, AU - Wang,Jing, AU - Zhou,Ru, AU - Qi,Xue, AU - Liu,Yue, AU - Ma,Lin, AU - Niu,Yang, AU - Sun,Tao, AU - Li,Yu-Xiang, AU - He,Yan-Ping, AU - Yu,Jian-Qiang, Y1 - 2017/05/09/ PY - 2017/03/11/received PY - 2017/05/03/accepted PY - 2017/5/11/pubmed PY - 2018/8/28/medline PY - 2017/5/11/entrez KW - Hippocampal neurons KW - Oxygen and glucose deprivation KW - Oxysophocarpine KW - Pro-inflammatory mediators SP - 529 EP - 540 JF - Cellular and molecular neurobiology JO - Cell. Mol. Neurobiol. VL - 38 IS - 2 N2 - 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 [Ca2+]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 [Ca2+]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. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/28488010/Neuroprotective_Effect_of_Oxysophocarpine_by_Modulation_of_MAPK_Pathway_in_Rat_Hippocampal_Neurons_Subject_to_Oxygen_Glucose_Deprivation_and_Reperfusion_ L2 - https://doi.org/10.1007/s10571-017-0501-5 DB - PRIME DP - Unbound Medicine ER -