Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB.

摘要: Homoisoflavonoids constitute a small class of natural products. In the present study, we investigated anti-inflammatory effect sappanone A (SPNA), homoisoflavanone that is isolated from heartwood Caesalpinia sappan (Leguminosae), in murine macrophages. SPNA inhibited production nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin-6 (IL-6) as well expression inducible synthase (iNOS), cyclooxygenase-2 (COX-2) IL-6 lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, protected C57BL/6 mice LPS-induced mortality. Treatment cells with induced heme oxygenase (HO)-1 protein mRNA increased nuclear translocation factor-E2-related factor 2 (Nrf2) Nrf2 target genes such NAD(P)H:quinone oxidoreductase 1 (NQO1). Knockdown by siRNA blocked SPNA-mediated HO-1 induction. SB203580, p38 mitogen-activated kinase (MAPK) inhibitor, SPNA-induced Nrf2, suggesting induces activating through MAPK pathway. Consistent notion Nrf2/HO-1 pathway has properties, inhibiting significantly abrogated effects LPS-stimulated suppressed κB (NF-κB) activation via Ser 536 phosphorylation transcriptional activity RelA/p65 subunit NF-κB. Taken together, these findings suggest exerts its modulating NF-κB pathways, may be valuable compound to prevent or treat inflammatory diseases.