title: Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine.
abstract: Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Department of Emergency Medicine, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Jiann-Hwa
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Taiwan; Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Taiwan.
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. Electronic address: thtsai@ym.edu.tw.
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy / Q000473:pathology; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001713:Biphenyl Compounds; C497251:Ddit3 protein, rat; D007202:Indicators and Reagents; D017705:Lignans; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C005498:magnolol; D051742:Transcription Factor CHOP; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D051058:Oncogene Protein v-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Akt; Inducible NO synthase; Magnolol; NF-κB; Stroke animal model; p38 mitogen-activated protein kinases