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

Mollugin, a bioactive phytochemical isolated from Rubia 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 a...

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Bibliographic Details
Published in:European journal of pharmacology 2011-03, Vol.654 (3), p.226-234
Main Authors: Jeong, Gil-Saeng, Lee, Dong-Sung, Kim, Dong-Chun, Jahng, Yurngdong, Son, Jong-Keun, Lee, Seung-Ho, Kim, Youn-Chul
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - drug effects
Animals
Anti-inflammation
anti-inflammatory activity
anti-inflammatory agents
Anti-Inflammatory Agents - pharmacology
anticarcinogenic activity
antimutagenic activity
Antioxidants - pharmacology
antiviral properties
Biological and medical sciences
BV2
Cell Line
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cytokines - metabolism
Enzyme Induction - drug effects
Gene Expression Regulation, Enzymologic - drug effects
Glutamic Acid - toxicity
heme oxygenase (biliverdin-producing)
Heme oxygenase (HO)-1
Heme Oxygenase-1 - biosynthesis
Heme Oxygenase-1 - metabolism
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - enzymology
Hippocampus - metabolism
HT22
inducible nitric oxide synthase
interleukin-6
Lipopolysaccharides - pharmacology
MAP Kinase Signaling System - drug effects
Medical sciences
Mice
Microglia - cytology
Microglia - drug effects
Microglia - enzymology
Microglia - metabolism
mitogen-activated protein kinase
Mollugin
neurodegenerative diseases
Neuropharmacology
Neuroprotection
Neuroprotective agent
Neuroprotective Agents - pharmacology
neuroprotective effect
neurotoxicity
NF-E2-Related Factor 2 - metabolism
Oxidative Stress - drug effects
p38 Mitogen-Activated Protein Kinases - metabolism
Pharmacology. Drug treatments
platelet aggregation
prostaglandin synthase
Pyrans - pharmacology
reactive oxygen species
Reactive Oxygen Species - metabolism
Rubia
Rubia cordifolia
Rubiaceae
tumor necrosis factor-alpha
Up-Regulation - drug effects
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Summary:Mollugin, a bioactive phytochemical isolated from Rubia 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-α 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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2010.12.027