Xanthotoxol exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

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.

• Authors: Wei He, Weiwei Chen, Yumei Zhou, Yuantong Tian, Fang Liao
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 33 Issue 5 Pg. 715-22 (Jul 2013) ISSN: 1573-6830 [Electronic] United States
• PMID: 23619720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Furocoumarins
• Neuroprotective Agents
• Transcription Factor RelA
• xanthotoxol
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Blood-Brain Barrier (drug effects, pathology)
• Brain Edema (complications, drug therapy, enzymology, pathology)
• Brain Ischemia (complications, drug therapy, pathology)
• Cell Nucleus (drug effects, metabolism)
• Cerebral Cortex (drug effects, enzymology, pathology)
• Cerebral Infarction (complications, drug therapy, enzymology, pathology)
• Cyclooxygenase 2 (metabolism)
• Cytokines (metabolism)
• Disease Models, Animal
• Furocoumarins (pharmacology, therapeutic use)
• Inflammation (complications, pathology)
• Male
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Permeability (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications, drug therapy, enzymology, pathology)
• Transcription Factor RelA (metabolism)