Cellular and Molecular Neurobiology

, Volume 33, Issue 5, pp 715–722

Xanthotoxol Exerts Neuroprotective Effects Via Suppression of the Inflammatory Response in a Rat Model of Focal Cerebral Ischemia

  • Wei He
  • Weiwei Chen
  • Yumei Zhou
  • Yuantong Tian
  • Fang Liao
Original Paper

Abstract

We previously found that xanthotoxol, one of the major active ingredients in Cnidium monnieri (L.) Cusson, exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema, inhibiting the neutrophil infiltration, and decreasing the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin. The present study was designed to further determine the possible mechanisms of action of neuroprotective properties of xanthotoxol after cerebral ischemia. Transient focal cerebral ischemia/reperfusion model in male Sprague–Dawley rats was induced by 2-h middle cerebral artery occlusion followed by 24-h reperfusion. Xanthotoxol (5 and 10 mg/kg) or vehicle were administered intraperitoneally at 1 and 12 h after the onset of ischemia. At 24 h after reperfusion, we assessed the effect of xanthotoxol on the blood–brain barrier (BBB) permeability, the production of pro-inflammatory mediators such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-8, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the p65 subunit of the transcription factor, nuclear factor-κB (NF-κB) in the cortex after ischemic insult. The results showed that xanthotoxol treatment significantly attenuated BBB disruption, reduced the IL-1β, TNF-α, IL-8 and NO level, and attenuated the iNOS activity compared with vehicle-treated animals. Further, xanthotoxol treatment also significantly prevented the ischemia/reperfusion-induced increase in the protein expression of iNOS, COX-2, and the nuclear NF-κB p65. These results, taken together with those of our previous study, suggest that the neuroprotection may be attributed to the ability of xanthotoxol to attenuate the expression of pro-inflammatory mediators and thereby inhibit the inflammatory response after cerebral ischemia.

Keywords

Xanthotoxol Cerebral ischemia/reperfusion Inflammatory response 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Wei He
    • 1
  • Weiwei Chen
    • 1
  • Yumei Zhou
    • 1
  • Yuantong Tian
    • 1
  • Fang Liao
    • 1
  1. 1.Key Laboratory of Cerebrovascular Pharmacology of Jiangxi Province, Department of PharmacologyGannan Medical CollegeGanzhouPeople’s Republic of China

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