title: 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.affiliation: Key Laboratory of Cerebrovascular Pharmacology of Jiangxi Province, Department of Pharmacology, Gannan Medical College, Ganzhou, People's Republic of China. hewei8286291@yahoo.com.cn
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yuantong
authors.initials: Y
authors.lastname: Tian
authors.forename: Fang
authors.initials: F
authors.lastname: Liao
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D011564:Furocoumarins / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D011564:Furocoumarins; D018696:Neuroprotective Agents; D051996:Transcription Factor RelA; C021768:xanthotoxol; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat