Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats. 2014

Nodoka Yasuda, and Takayuki Ishii, and Dai Oyama, and Tatsuya Fukuta, and Yurika Agato, and Akihiko Sato, and Kosuke Shimizu, and Tomohiro Asai, and Tomohiro Asakawa, and Toshiyuki Kan, and Shizuo Yamada, and Yasushi Ohizumi, and Naoto Oku
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

Nobiletin, a citrus polymethoxylated flavone, is reported to possess various pharmacological activities such as anticancer, anti-inflammation, and antioxidant effects. Recently, nobiletin was shown to provide therapeutic benefit for the treatment of Alzheimer׳s disease by activating cAMP-response element-binding protein (CREB). In the present study, we investigated whether nobiletin could protect the brain against ischemia-reperfusion (I/R) injury and improve functional outcome in cerebral I/R model rats, since CREB activation is known to protect neuronal cells in cerebral ischemia. Nobiletin was injected twice at 0 and 1h after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. Cerebral I/R induced prominent brain damage in the ischemic hemisphere of t-MCAO rat brains; however, nobiletin treatment significantly reduced the infarct volume and suppressed the brain edema. Immunohistochemical and TUNEL staining indicated that nobiletin treatment significantly suppressed neutrophil invasion into the ischemic region and significantly decreased apoptotic brain cell death in ischemic hemisphere, suggesting that the anti-inflammatory effect and anti-apoptotic effect should be regarded as the neuroprotective mechanism of nobiletin. Moreover, nobiletin treatment ameliorated motor functional deficits in the ischemic rats compared with those deficits of the vehicle-treated group. These results indicate that nobiletin is a potential neuroprotectant for the treatment of cerebral I/R injury.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D001929 Brain Edema Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6) Brain Swelling,Cerebral Edema,Cytotoxic Brain Edema,Intracranial Edema,Vasogenic Cerebral Edema,Cerebral Edema, Cytotoxic,Cerebral Edema, Vasogenic,Cytotoxic Cerebral Edema,Vasogenic Brain Edema,Brain Edema, Cytotoxic,Brain Edema, Vasogenic,Brain Swellings,Cerebral Edemas, Vasogenic,Edema, Brain,Edema, Cerebral,Edema, Cytotoxic Brain,Edema, Cytotoxic Cerebral,Edema, Intracranial,Edema, Vasogenic Brain,Edema, Vasogenic Cerebral,Swelling, Brain
D002546 Ischemic Attack, Transient Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6) Brain Stem Ischemia, Transient,Cerebral Ischemia, Transient,Crescendo Transient Ischemic Attacks,Transient Ischemic Attack,Anterior Circulation Transient Ischemic Attack,Brain Stem Transient Ischemic Attack,Brain TIA,Brainstem Ischemia, Transient,Brainstem Transient Ischemic Attack,Carotid Circulation Transient Ischemic Attack,Posterior Circulation Transient Ischemic Attack,TIA (Transient Ischemic Attack),Transient Ischemic Attack, Anterior Circulation,Transient Ischemic Attack, Brain Stem,Transient Ischemic Attack, Brainstem,Transient Ischemic Attack, Carotid Circulation,Transient Ischemic Attack, Posterior Circulation,Transient Ischemic Attack, Vertebrobasilar Circulation,Transient Ischemic Attacks, Crescendo,Vertebrobasilar Circulation Transient Ischemic Attack,Attack, Transient Ischemic,Attacks, Transient Ischemic,Brainstem Ischemias, Transient,Cerebral Ischemias, Transient,Ischemia, Transient Brainstem,Ischemia, Transient Cerebral,Ischemias, Transient Brainstem,Ischemias, Transient Cerebral,Ischemic Attacks, Transient,TIA, Brain,TIAs (Transient Ischemic Attack),Transient Brainstem Ischemia,Transient Cerebral Ischemia,Transient Cerebral Ischemias,Transient Ischemic Attacks
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000894 Anti-Inflammatory Agents, Non-Steroidal Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents

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