Arylbenzofuran isolated from Dalbergia odorifera suppresses lipopolysaccharide-induced mouse BV2 microglial cell activation, which protects mouse hippocampal HT22 cells death from neuroinflammation-mediated toxicity.
Neuroinflammation is a key mechanism against infection, injury, and trauma in the central nervous system (CNS). The heartwood of Dalbergia odorifera T. Chen is an important source of traditional Korean and Chinese medicines. (2R, 3R)-Obtusafuran (1) and isoparvifuran (2) are arylbenzofuran compounds isolated from D. odorifera. This study determined the efficacy of (1) and (2) in modulating the regulation of anti-inflammatory activity through the upregulation of heme oxygenase (HO)-1 in BV2 microglia. Compound (1) inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), cyclooxygenase (COX)-2, and COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated mouse BV2 microglia. (2R, 3R)-Obtusafuran (1) also reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production, and these anti-neuroinflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of inhibitor of nuclear factor kappa B-α (IκB-α), and nuclear factor kappa B nuclear (NF-κB) translocation and DNA binding activity. In addition, (1) 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 (1) on the proinflammatory mediators and proteins were associated with the induction of HO-1 expression. Activated microglia-mediated cell death of mouse hippocampal HT22 cells was significantly repressed by (1). Our data suggest that (2R, 3R)-obtusafuran (1) 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
College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 704-701, Republic of Korea. Electronic address: gsjeong@kmu.ac.kr.
Gil-Saeng
GS
Jeong
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D035782:Dalbergia / Q000737:chemistry*; D051547:Heme Oxygenase-1 / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides; D055670:Medicine, Korean Traditional; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000276:immunology / Q000517:prevention & control; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C000593122:isoparvifuran; C000593121:obtusafuran; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
(2R, 3R)-Obtusafuran; BV2 microglia; Dalbergia odorifera; Heme oxygenase-1; Neuroinflammation; Neuroprotection