title: Rosmarinic acid protects against experimental diabetes with cerebral ischemia: relation to inflammation response.
abstract: BACKGROUND
  Inflammatory activation plays a vital role in the pathophysiological mechanisms of stroke, exerting deleterious effects on the progression of tissue damage and may lead to the vascular damage in diabetes. The objectives of this study were to determine the effects of rosmarinic acid (RA) on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic diabetic stroke in vivo.
  
  
  METHODS
  For oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were incubated with RA. For an in vivo experiment, diabetic rats were subjected to middle cerebral artery occlusion (MACO) for 40 minutes followed by reperfusion for 23 h.
  
  
  RESULTS
  Treatment of SH-SY5Y cells with RA reduced the OGD-induced apoptosis and cytotoxicity, blocked TNF-α-induced nuclear transcription factor κB (NF-κB) activation, and decreased high-mobility group box1 (HMGB1) expression. At doses higher than 50 mg/kg, RA produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). RA (50 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h and 5 h after I/R. RA 50 mg/kg attenuated histopathological damage, decreased brain edema, inhibited NF-κB activation and reduced HMGB1 expression.
  
  
  CONCLUSIONS
  These data show that RA protects the brain against I/R injury with a favorable therapeutic time-window by alleviating diabetic cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and the NF-κB signaling pathway.
authors: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, People's Republic of China.
authors: Haiyun
authors: H
authors: Luan
authors: Zechun
authors: Z
authors: Kan
authors: Yong
authors: Y
authors: Xu
authors: Changjun
authors: C
authors: Lv
authors: Wanglin
authors: W
authors: Jiang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use*; D053630:Depsides / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D000097123:Rosmarinic Acid