title: Involvement of heme oxygenase-1 induction in the cytoprotective and immunomodulatory activities of 6,4'-dihydroxy-7-methoxyflavanone in murine hippocampal and microglia cells.
abstract: 6,4'-Dihydroxy-7-methoxyflavanone (DMF), a biologically active compound, was isolated from the heartwood of Dalbergia odorifera T. Chen (Leguminosae). The present study proposed to examine the role of DMF as an anti-oxidative and anti-inflammatory heme oxygenase-1 (HO-1) inducer in mouse hippocampal HT22 cells and BV2 microglia cells. The effect of DMF on cell viability was determined by MTT assay and the effects of DMF on pro-inflammatory enzymes and cytokines were analyzed by western blot and ELISA. Parameters such as DMF induced HO-1 protein immunocontents, HO activity and mitogen-activated protein kinases (MAPK) activation were also measured. DMF increased cellular resistance to oxidative injury caused by glutamate-induced cytotoxicity in HT22 cells, via JUN N-terminal kinase (JNK) pathway dependent HO-1 expression. Furthermore, DMF suppressed the lipopolysaccharide (LPS)-induced expression of pro-inflammatory enzymes and inflammatory mediators in BV2 microglia. DMF suppressed production of nitric oxide (NO), prostaglandin E2 (PGE(2)), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), through extracellular signal-regulated kinase (ERK) pathway dependent HO-1 expression. This study indicates that DMF effectively modulates the regulation of anti-oxidative and anti-inflammatory action, via up-regulation of HO-1 in HT22 cells and BV2 microglia. These results suggest that DMF possesses therapeutic potentials against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.
authors: Standardized Material Bank for New Botanical Drugs; College of Pharmacy, Wonkwang University, Iksan, Republic of Korea.
authors: Bin
authors: B
authors: Li
authors: Dong-Sung
authors: DS
authors: Lee
authors: Gil-Saeng
authors: GS
authors: Jeong
authors: Youn-Chul
authors: YC
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; 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*; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000166:cytology*; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C571779:6,4'-dihydroxy-7-methoxyflavanone; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D044950:Flavanones; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D051547:Heme Oxygenase-1; C028610:flavanone