title: Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide‑stimulated BV2 microglia.
abstract: Microglial activation has been recognized as being vital in the pathogenesis of several neurodegenerative disorders. Therefore, the identification of therapeutic drugs to prevent microglial activation and thus protect against inflammation‑mediated neuronal injury, is required. In the present study, dextromethorphan (DM), a compound widely used in antitussive remedies that has been demonstrated to possess neuroprotective effects, was shown to reduce proinflammatory mediator production in lipopolysaccharide (LPS)‑stimulated BV2 mouse microglial cells. Western blot analysis revealed that DM markedly suppressed the activation of nuclear factor‑κB (NFκB), caspase‑3 signaling and the expression of another inflammation‑inducing factor, heat shock protein 60 (HSP60) and heat shock factor‑1, induced by LPS in BV2 cells. Results from ELISA assay demonstrated that DM reduced the release of HSP60, nitric oxide (NO), inducible NO synthase, tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 induced by LPS in BV2 microglia. These results were confirmed by immunofluorescence, suggesting that DM may exert a neuroprotective and anti‑inflammatory effect by inhibiting microglial activation through the HSP60‑NFκB signaling pathway. Therefore, DM may offer substantial therapeutic benefits in the treatment of neurodegenerative diseases that are accompanied by microglial activation.
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Neurology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Bai
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Feijia
authors.initials: F
authors.lastname: Ding
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Ma
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Ningxia Key Laboratory of Cranial Cerebral Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018834:Chaperonin 60 / Q000032:analysis; D003915:Dextromethorphan / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D018834:Chaperonin 60; C557066:Hspd1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003915:Dextromethorphan; D052247:Nitric Oxide Synthase Type II