title: Pretreatment of 6-shogaol attenuates oxidative stress and inflammation in middle cerebral artery occlusion-induced mice.
abstract: 6-Shogaol can be extracted from ginger and has been shown to exert anti-inflammatory and antioxidant activities, which are potentially relevant to the treatment of central nervous system disorders. Oxidative stress and inflammation are closely associated with ischemic injury and can eventually result in neuronal death. The aim of this study was to evaluate if 6-shogaol exerts neuroprotective activity. To this end, we determined its effects on oxidative stress and inflammation in a mouse model of middle cerebral artery occlusion (MCAO)-induced brain damage. In this model, MCAO was induced in C57BL/6 mice (30-35g, 9 weeks) for 1h, followed by 24h reperfusion. Mice were treated orally with 6-shogaol (0.1ml, 5 or 20mg/kg) once daily for 7 consecutive days prior to MCAO. We found that 6-shogaol significantly reduced neurological deficit scores and the mean infarct area. Moreover, 6-shogaol improved the behavioral deficits in the MCAO group. In addition, 6-shogaol pretreatment dampened MCAO-mediated production of reactive oxygen species and inflammatory cytokines. Mechanistic studies revealed that 6-shogaol inhibits the cysteinyl leukotriene 1 receptor (CysLT1R) and mitogen-activated protein kinase (MAPK) signaling proteins, thus providing a potential pharmacological mechanism for our observations. These results suggest that 6-shogaol can ameliorate the outcomes of MCAO and could thus be used as a potential preventive of stroke.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan 54596, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Na
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan 54596, Republic of Korea.
authors.forename: Kibbeum
authors.initials: K
authors.lastname: Song
authors.affiliation: Central Research and Development, Between Inc., Iksan 54596, Republic of Korea.
authors.forename: Ju-Woon
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan 54596, Republic of Korea. Electronic address: raios@hanmail.net.
authors.forename: Sokho
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, 79 Gobongro, Iksan 54596, Republic of Korea; Central Research and Development, Between Inc., Iksan 54596, Republic of Korea. Electronic address: jkwon@jbnu.ac.kr.
authors.forename: Jungkee
authors.initials: J
authors.lastname: Kwon
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002396:Catechols / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000150:complications; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002396:Catechols; D016207:Cytokines; D017382:Reactive Oxygen Species; D018077:Receptors, Leukotriene; D008315:Malondialdehyde; C040115:shogaol; D020928:Mitogen-Activated Protein Kinases; C083169:leukotriene D4 receptor
keywords: 6-Shogaol; Inflammation; Ischemia; MCAO; Oxidative stress