title: Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke.
abstract: Oxidative stress and inflammation play an integral role in the pathogenesis of cerebral ischemia that leads to a cascade of events culminating in the death of neurons and their supporting structures. The signaling pathways that link these events are not fully understood. Recent studies have demonstrated a close link between the nuclear factor-κB (NF-κB) signaling pathway and cerebral ischemia/reperfusion (I/R)-induced inflammation. Flavonoids have been suggested to exert human health benefits by anti-oxidant and anti-inflammatory mechanisms. In this study we undertook a pharmacological approach to investigate the ability of naringenin, a potent flavonoid, to prevent oxidative stress and NF-κB-mediated inflammatory brain damage in the rat model of focal cerebral I/R injury. To test this hypothesis, male Wistar rats were pretreated with naringenin once daily for 21 days and then subjected to 1h of middle cerebral artery occlusion followed by 23 h of reperfusion. Naringenin treatment successfully upregulates the antioxidant status, decreases the infarct size and lowers the levels of myeloperoxidase, nitric oxide and cytokines, besides functional recovery returned close to the baseline. Moreover, immunohistochemical and Western blot analyses clearly demonstrated that naringenin treatment limits glial activation and downregulates the NF-κB expression level and their target genes. These results show, prophylactic treatment with naringenin improved functional outcomes and abrogated the ischemic brain injury by suppressing NF-κB-mediated neuroinflammation. The present study suggests that naringenin may be used as a potential neuroprotectant in patients at high risk of ischemic stroke.
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (Fund for the Improvement of Science and Technology Sponsored by DST and Special Assistance Programme Sponsored by UGC), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: S S
authors.initials: SS
authors.lastname: Raza
authors.forename: M M
authors.initials: MM
authors.lastname: Khan
authors.forename: A
authors.initials: A
authors.lastname: Ahmad
authors.forename: M
authors.initials: M
authors.lastname: Ashafaq
authors.forename: F
authors.initials: F
authors.lastname: Islam
authors.forename: A P
authors.initials: AP
authors.lastname: Wagner
authors.forename: M M
authors.initials: MM
authors.lastname: Safhi
authors.forename: F
authors.initials: F
authors.lastname: Islam
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D044950:Flavanones / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018737:Hand Strength / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015398:Signal Transduction / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016207:Cytokines; D044950:Flavanones; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D018696:Neuroprotective Agents; D047492:Peroxisome Proliferator-Activated Receptors; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D009195:Peroxidase; D005978:Glutathione; C005273:naringenin