Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells

Title
Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells
Author(s)
이승호손종근장영동김윤철[김윤철]김동춘[김동춘]이동성[이동성]정길생[정길생]
Keywords
NITRIC-OXIDE PRODUCTION; OXIDATIVE STRESS; RUBIA-CORDIFOLIA; CARBON-MONOXIDE; INFLAMMATORY MEDIATORS; RAW264.7 MACROPHAGES; GENE-EXPRESSION; RAT-BRAIN; TNF-ALPHA; KAPPA-B
Issue Date
201103
Publisher
ELSEVIER SCIENCE BV
Citation
EUROPEAN JOURNAL OF PHARMACOLOGY, v.654, no.3, pp.226 - 234
Abstract
Mollugin, a bioactive phytochemical isolated from Rabic, cordifolia L (Rubiaceae), exhibits antimutagenic activity, antitumor activity, antiviral activity, and inhibitory activity in arachidonic acid- and collagen-induced platelet aggregation. In this study, we investigated the effects of mollugin as a neuroprotective agent in glutamate-induced neurotoxicity in the mouse hippocampal HT22 cell line and as an anti-inflammatory agent in lipopolysaccharide-induced microglial activation in BV2 cells. Mollugin showed potent neuroprotective effects against glutamate-induced neurotoxicity and reactive oxygen species generation in mouse hippocampal HT22 cells. In addition, the anti-inflammatory effects of mollugin were demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-alpha and interleukin-6). Furthermore, we found that the neuroprotective and anti-inflammatory effects of mollugin were linked to the up-regulation of the expression of heme oxygenase (HO)-1 and the activity of HO in HT22 and BV2 cells. In addition, the effects of mollugin resulted in the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) in HT22 and BV2 cells. Furthermore, mollugin also activated the p38 mitogen-activated protein kinase (MAPK) pathway both in HT22 and BV2 cells. These results suggest that mollugin may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation. (C) 2011 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/25560http://dx.doi.org/10.1016/j.ejphar.2010.12.027
ISSN
0014-2999
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약학대학 > 약학부 > Articles
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