Neuroprotective effects of INM-176 against lipopolysaccharide-induced neuronal injury

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2012-05, Vol.101 (3), p.427-433
• Main Authors: Park, Se Jin, Jung, Hoon-Ji, Son, Min-Sook, Jung, Jun Man, Kim, Dong Hyun, Jung, In Ho, Cho, Yong-Baik, Lee, Eunjoo H., Ryu, Jong Hoon
• Format: Article
• Language: English
• Subjects: Angelica; Animals; Anti-inflammation; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Astrocytes - drug effects; Astrocytes - physiology; Avoidance Learning - drug effects; Cells, Cultured; Cognition - drug effects; Cyclooxygenase 2 - metabolism; Hippocampus - drug effects; Hippocampus - injuries; Hippocampus - physiopathology; INM-176; Interleukin-1beta - biosynthesis; Lipopolysaccharide; Lipopolysaccharides - toxicity; Maze Learning - drug effects; Memory; Mice; Mice, Inbred ICR; Microglia - drug effects; Microglia - physiology; Neuroprotection; Neuroprotective Agents - pharmacology; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - metabolism; Plant Extracts - pharmacology; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2012.02.003

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 (1μg/2μl, 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. ► INM-176 suppresses LPS-induced release of proinflammatory and cytotoxic factors. ► INM-176 blocked LPS-induced neuronal damage in the hippocampal slice culture. ► INM-176 ameliorates LPS-induced cognitive impairment via blockade of gliosis.