title: Neuroprotective effects of INM-176 against lipopolysaccharide-induced neuronal injury.
abstract: Neuroinflammation plays a critical role in the etiology of chronic neurodegenerative diseases such as Alzheimer's disease. INM-176 is a standardized ethanolic extract of Angelica gigas, which has been traditionally used as a tonic to treat anemia. In the present study, we investigated whether INM-176 exhibits neuroprotective activities against lipopolysaccharide (LPS)-induced neuronal damage in vitro and in vivo. In primary microglial cells, INM-176 significantly inhibited LPS-induced nitric oxide release and expression of tumor necrosis factor-α and interleukin-1β. The expression levels of inducible nitric oxide synthase and cylcooxygenase-2 in BV2 microglial cells were markedly upregulated by LPS, but this increased expression was counteracted by INM-176. LPS-mediated neuronal damage in an organotypic hippocampal slice culture was also attenuated by the administration of INM-176. In addition, LPS (1 μg/2 μl, i.c.v.)-induced cognitive dysfunction in mice, as determined by passive avoidance and Y-maze tasks, was significantly attenuated by the administration of INM-176. Furthermore, the activation of microglia or astrocytes by LPS in the hippocampal regions of mice was suppressed by INM-176. These results suggest that the neuroprotective and cognition ameliorating effects of INM-176 against LPS-induced damage are mediated, in part, by its anti-inflammatory activities.
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, #1 Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Hoon-Ji
authors.initials: HJ
authors.lastname: Jung
authors.forename: Min-Sook
authors.initials: MS
authors.lastname: Son
authors.forename: Jun Man
authors.initials: JM
authors.lastname: Jung
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: In Ho
authors.initials: IH
authors.lastname: Jung
authors.forename: Yong-Baik
authors.initials: YB
authors.lastname: Cho
authors.forename: Eunjoo H
authors.initials: EH
authors.lastname: Lee
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D029969:Angelica; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2