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

International Immunopharmacology
2013.0

Abstract

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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production, and suppressed the phosphorylation and degradation of IkappaB-alpha 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-alpha, and IL-1beta, and nuclear factor kappa B (NF-kappaB) 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. CI - (c) 2013.

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