title: Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells.
abstract: 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.
authors.affiliation: Zoonosis Research Center, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Dong-Chun
authors.initials: DC
authors.lastname: Kim
authors.forename: Yurngdong
authors.initials: Y
authors.lastname: Jahng
authors.forename: Jong-Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D011714:Pyrans; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; C046245:rubimaillin; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases