title: Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons.
abstract: Neurons are damaged following prolonged exposure to high concentrations of corticosterone, particularly during chronic inflammatory and immune diseases. One of the main mechanisms underlying neuronal injury is apoptosis. In the present study the neuroprotective effects of icariin, an active natural ingredient from the Chinese plant Epimedium sagittatum maxim against corticosterone-induced apoptosis were examined in primary cultured rat hippocampal neuronal cells. Pre-treatment of neuronal cells with icariin suppressed corticosterone-induced cytotoxicity in a dose-dependent manner. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling assay (TUNEL) labeling demonstrated that icariin significantly reduced TUNEL-positive cell numbers induced by exposure of cultured neurons to corticosterone. Moreover, icariin markedly inhibited corticosterone-induced mitochondrial dysfunction, including improved mitochondrial membrane potential and inhibition of caspase-3 activation. Using western blot analysis, corticosterone activated p38MAPK, extracellular regulated kinase 1/2(ERK1/2) ,and c-jun N-terminal protein kinase 1(JNK1) ,while icariin blocked p38 MAPK, but not JNK1 or ERK1/2. Pharmacological approaches showed that the activation of p38MAPK plays a critical role in corticosterone-induced mitochondrial dysfunction and apoptosis. Taken together, the present results suggest that the protective effects of icariin on apoptosis in hippocampal neuronal cells are potentially mediated through blockade of p38 MAPK phosphorylation.
authors.affiliation: Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai, China 200040.
authors.forename: Baojun
authors.initials: B
authors.lastname: Liu
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhang
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Jiang
authors.initials: J
authors.lastname: Tao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Huang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
authors.forename: Yuxue
authors.initials: Y
authors.lastname: Cao
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Dong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D003345:Corticosterone / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D018696:Neuroprotective Agents; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D018696:Neuroprotective Agents; D011725:Pyridines; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C093642:SB 203580; C056599:icariin; D003345:Corticosterone