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Planta Med 2013; 79(11): 916-923
DOI: 10.1055/s-0032-1328705
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Anti-apoptotic and Neuroprotective Effects of Oxysophoridine on Cerebral Ischemia Both In Vivo and In Vitro

Chen Rui   *
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
2   Department of Pharmacy, Women and Childrenʼs Hospital of Jinzhou, Jinzhou, China
,
Li Yuxiang   *
3   College of Nursing, Ningxia Medical University, Yinchuan, China
4   Shanghai Pudong New Area Gongli Hospital, Shanghai, China
,
Jiang Ning
4   Shanghai Pudong New Area Gongli Hospital, Shanghai, China
,
Ma Ningtian
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
,
Zhu Qingluan
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
,
Hao Yinju
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
5   Ningxia Engineering and Technology Research Center of Hui Medicine Modernization, Yinchuan, China
,
Zhou Ru
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
6   Ningxia Collaborative Innovation Center of Hui Medicine, Yinchuan, China
,
Ma Lin
7   Ningxia Key Lab of Craniocerbral Diseases of Ningxia Hui Autonomous Region, Yinchuan, China
,
Sun Tao
7   Ningxia Key Lab of Craniocerbral Diseases of Ningxia Hui Autonomous Region, Yinchuan, China
,
Yu Jianqiang
1   Department of Pharmacology, Ningxia Medical University, Yinchuan, China
8   Key Laboratory of Hui Medicine Modernization, Ministry of Education, Yinchuan, China
› Author Affiliations
Further Information

Publication History

received 04 January 2013
revised 16 May 2013

accepted 17 May 2013

Publication Date:
27 June 2013 (online)

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Abstract

In this study, we investigated the neuroprotective effect of oxysophoridine on ischemia and ischemia-like insults. Protection by oxysophoridine was studied at the in vivo level using a model of middle cerebral artery occlusion in mice and at the in vitro level using primary rat hippocampal neuronal cultures exposed to oxygen-glucose deprivation, a model of ischemia-like injury. The behavioral test was performed by using the neurological scores. The infarction volume of brain was assessed in the brain slices stained with 2,3,5-triphenyl tetrazolium chloride. The neuron apoptosis was evaluated by Hoechst 33342 staining. The morphological change in the neurons was examined using a Transmission Electron Microscope (TEM or EM). To evaluate neuron apoptosis, caspase-3, -9, and − 8 activities were measured using assay kits with an ELISA reader. The Western blotting assay was used to evaluate the release of cytochrome c and expression of caspase-3, Bcl-2, and Bax proteins. The quantitative real-time PCR assay was used to evaluate the release of cytochrome c and the expression of caspase-3 mRNA. Oxysophoridine-treated groups (62.5, 125, 250 mg/kg) markedly reduced neurological deficit scores and infarct volumes. Treatment with oxysophoridine (5, 20, 80 µmol/L) significantly attenuated neuronal damage, with evidence of decreased cell apoptosis and decreased cell morphologic impairment. Furthermore, treatment with oxysophoridine could effectively downregulate the expression of cytochrome c and caspase-3 in both mRNA and protein levels, and Bax in the protein level, and induce an increase of Bcl-2 in the protein level. The caspase-3, -9, and -8 activities were also inhibited. These findings suggested that oxysophoridine may be a potential neuroprotective agent for cerebral ischemia injury.

Key words

oxysophoridine - cerebral ischemia - middle cerebral artery occlusion - oxygen-glucose deprivation - apoptosis - neuroprotection - Siphocampylus verticillatus - Campanulaceae

* These authors contributed equally to this work.


 

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