Inhibitory effect of 9-hydroxy-6,7-dimethoxydalbergiquinol from Dalbergia odorifera on the NF-κB-related neuroinflammatory response in lipopolysaccharide-stimulated mouse BV2 microglial cells is mediated by heme oxygenase-1.
The heartwood of Dalbergia odorifera T. Chen (Leguminosae) is an important source of traditional Korean and Chinese medicines. 9-Hydroxy-6,7-dimethoxydalbergiquinol (HDDQ), a compound isolated from D. odorifera, has various biological activities. The aim of this study was to determine the efficacy of HDDQ in modulating the regulation of anti-inflammatory activity through the upregulation of heme oxygenase (HO)-1 in BV2 microglia. HDDQ inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), and the production of cyclooxygenase (COX)-2 and COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated mouse BV2 microglia. HDDQ also reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production, and suppressed the phosphorylation and degradation of IκB-α and the nuclear translocation of p65 in mouse BV2 microglia in response to LPS. Furthermore, HDDQ upregulated HO-1 expression via nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in mouse BV2 microglia. Using tin protoporphyrin (SnPP), an HO activity inhibitor, we verified that the inhibitory effects of HDDQ on the proinflammatory mediators NO, PGE2, TNF-α, and IL-1β, and nuclear factor kappa B (NF-κB) DNA-binding activity are associated with the induction of HO-1 expression. Our data suggest that HDDQ has therapeutic potential against neurodegenerative diseases caused by neuroinflammation.
Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Republic of Korea.
Dong-Sung
DS
Lee
Bin
B
Li
Samell
S
Keo
Kyoung-Su
KS
Kim
Gil-Saeng
GS
Jeong
Hyuncheol
H
Oh
Youn-Chul
YC
Kim
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C000591712:9-hydroxy-6,7-dimethoxydalbergiquinol; D000498:Allyl Compounds; D000840:Anisoles; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D015232:Dinoprostone
9-hydroxy-6,7-dimethoxydalbergiquinol; BV2 microglia; Dalbergia odorifera; Heme oxygenase-1; Neuroinflammation; Nuclear factor kappa B