title: Oxymatrine attenuated hypoxic-ischemic brain damage in neonatal rats via improving antioxidant enzyme activities and inhibiting cell death.
abstract: Oxymatrine (OMT), an active constituent of Chinese herb Sophora flavescens Ait, has been proved to possess anti-tumor, anti-oxidant, anti-inflammatory, and anti-apoptotic activities. Previous study has demonstrated that OMT had protective roles on multiple in vitro and in vivo brain injury models including regulation of apoptosis-related proteins caspase-3, Bax and Bcl-2. In this study, we investigated whether this protective effect could apply to neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with the left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37 °C. In sham group rats, neither ligation nor hypoxia was performed. After two successive days intraperitoneal injection with OMT (30, 60 and 120 mg/kg), Nimodipine (1 mg/kg), and saline, brain infarct volume was estimated, histomorphology changes were performed by hematoxylin-eosin (HE) staining as well as electron microscopy. In addition, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), as well as production of malondialdehyde (MDA) were assayed in ipsilateral hemisphere homogenates to evaluate the redox status after hypoxic-ischemic. Expression of apoptosis-related proteins Caspase-3, Bax and Bcl-2 in brain were analyzed by western-blot analysis and immunofluorescence. Administration of OMT significantly decreased brain infarct volume and the percentage of injured cells, and ameliorated histopathology and morphological injury as well. Furthermore, OMT obviously increased the activities of SOD, GSH-Px, CAT and T-AOC, and decreased MDA content. Western-blot analysis showed a marked decrease in Caspase-3 expression and increase in the ratio of Bcl-2/Bax after OMT (120 mg/kg) post-treatment as compared with hypoxic-ischemic group. These results suggest that OMT exerts a neuroprotective effect against hypoxic-ischemic brain damage in neonatal rats, which is likely to be mediated through increasing anti-oxidant enzyme activities and inhibiting cell death.
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Wan-Xia
authors.initials: WX
authors.lastname: Yao
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Hai-Qi
authors.initials: HQ
authors.lastname: Qiao
authors.affiliation: Medical Sci-tech Research Center, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Shu-Jing
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Ningxia Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: College of Nursing, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China; Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan 750004, China. Electronic address: yujq910315@163.com.
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Yu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D011807:Quinolizines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029909:Sophora; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000975:Antioxidants; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines
keywords: Antioxidant enzyme; Cell death; Hypoxic-ischemia; Neonatal; Neuroprotection; Oxymatrine