title: Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.
abstract: BACKGROUND
  Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats.
  
  
  METHODS
  Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function.
  
  
  RESULTS
  We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors.
  
  
  CONCLUSIONS
  All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yue-fei
authors.initials: YF
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
authors.forename: Da-kuan
authors.initials: DK
authors.lastname: Gao
authors.forename: Luo-an
authors.initials: LA
authors.lastname: Fu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D031048:Cnidium / Q000737:chemistry; D003374:Coumarins / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002121:Calcium Channel Blockers; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C046627:osthol
keywords: Ischemia–reperfusion injury; Mitochondria; Neuroprotection; Oxidative stress