Cynandione A mitigates ischemic injuries in rats with cerebral ischemia.

Abstract

Cynandione A, an acetophenone from the roots of Cynanchum auriculatum and other species in the genus attenuates neurotoxicity of a variety of neurotoxic agents such as l-glutamate in vitro. In this study, we sought to further characterize the neuroprotective effects of cynandione A and other acetophenones from the roots of C. auriculatum in pheochromocytoma tumor cell line PC12 and investigate whether cynandione A protected against ischemic injuries in rats with experimentally induced cerebral ischemia. Viability assays using the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophen-yl)-2H-tetrazolium monosodium salt method and lactate dehydrogenase (LDH) release assays showed that cynandione A dose-dependently attenuated glutamate-induced cytotoxicity. Comparative proteomic analysis by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight MS/MS of PC12 cells treated with cynandione A showed 10 μM cynandione A caused broad changes in protein expression in PC12 cells including down-regulation of high mobility group box 1 (HMGB1) and dihydropyrimidinase-like 2 (DPYSL2). Immunoblotting studies showed that 10 μM cynandione A aborted glutamate-induced increase in DPYSL2 and HMGB1 levels in PC12 cells and 30 mg/kg cynandione A also attenuated the rise in HMGB1 levels and mitigated DPYSL2 cleavage in brain tissues of rats with cerebral ischemia. Furthermore, rats with cerebral ischemia treated with 30 mg/kg cynandione A exhibited markedly improved neurological deficit scores at 24 and 72 h compared with control and a 7.2% reduction in cerebral infarction size at 72 h (p < 0.05 vs. control). Our findings demonstrated that cynandione A mitigated ischemic injuries and should be further explored as a neuroprotective agent for ischemic stroke.

• Authors: Rongcai Yue, Xing Yuan, Xiaojun Liu, Jigang Zhang, Peng Jiang, Cheng He, Lei Shan, Yizhi Yu, Weidong Zhang
• Journal: Journal of neurochemistry (J Neurochem) Vol. 121 Issue 3 Pg. 451-64 (May 2012) ISSN: 1471-4159 [Electronic] England
• PMID: 22309483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Chemical References

• Biphenyl Compounds
• Free Radical Scavengers
• HMGB1 Protein
• Intercellular Signaling Peptides and Proteins
• Nerve Tissue Proteins
• Neuroprotective Agents
• Picrates
• collapsin response mediator protein-2
• cynandione A
• 1,1-diphenyl-2-picrylhydrazyl
• Glutathione Peroxidase
• Superoxide Dismutase
• Glutathione

Topics

• Animals
• Biphenyl Compounds (therapeutic use)
• Blotting, Western
• Brain (pathology)
• Brain Ischemia (drug therapy, pathology)
• Cell Survival (drug effects)
• Cynanchum (chemistry)
• Databases, Genetic
• Electrophoresis, Gel, Two-Dimensional
• Free Radical Scavengers (pharmacology)
• Glutathione (metabolism)
• Glutathione Peroxidase (metabolism)
• HMGB1 Protein (biosynthesis, genetics)
• Immunohistochemistry
• Intercellular Signaling Peptides and Proteins (biosynthesis, genetics)
• Male
• Nerve Tissue Proteins (biosynthesis, genetics)
• Neuroprotective Agents (therapeutic use)
• PC12 Cells
• Picrates
• Plant Roots (chemistry)
• Rats
• Rats, Sprague-Dawley
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Superoxide Dismutase (metabolism)