title: Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB.
abstract: Homoisoflavonoids constitute a small class of natural products. In the present study, we investigated the anti-inflammatory effect of sappanone A (SPNA), a homoisoflavanone that is isolated from the heartwood of Caesalpinia sappan (Leguminosae), in murine macrophages. SPNA inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin-6 (IL-6) as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, SPNA protected C57BL/6 mice from LPS-induced mortality. Treatment of RAW264.7 cells with SPNA induced heme oxygenase (HO)-1 protein and mRNA expression and increased nuclear translocation of the nuclear factor-E2-related factor 2 (Nrf2) as well as the expression of Nrf2 target genes such as
  quinone oxidoreductase 1 (NQO1). Knockdown of Nrf2 by siRNA blocked SPNA-mediated HO-1 induction. SB203580, p38 mitogen-activated protein kinase (MAPK) inhibitor, blocked SPNA-induced HO-1 expression and nuclear translocation of Nrf2, suggesting that SPNA induces HO-1 expression by activating Nrf2 through the p38 MAPK pathway. Consistent with the notion that the Nrf2/HO-1 pathway has anti-inflammatory properties, inhibiting HO-1 significantly abrogated the anti-inflammatory effects of SPNA in LPS-stimulated RAW264.7 cells. Moreover, SPNA suppressed LPS-induced nuclear factor κB (NF-κB) activation via inhibiting Ser 536 phosphorylation and transcriptional activity of RelA/p65 subunit of NF-κB. Taken together, these findings suggest that SPNA exerts its anti-inflammatory effect by modulating the Nrf2 and NF-κB pathways, and may be a valuable compound to prevent or treat inflammatory diseases.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Suhyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Sol-Yip
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Young-Yeon
authors.initials: YY
authors.lastname: Choo
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Okwha
authors.initials: O
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Phuong Thao
authors.initials: PT
authors.lastname: Tran
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea.
authors.forename: Cuong To
authors.initials: CT
authors.lastname: Dao
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea.
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea. Electronic address: jhlee36@kangwon.ac.kr.
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D029911:Caesalpinia; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008565:Membrane Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D014934:Wood
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D007529:Isoflavones; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C577686:interleukin-6, mouse; C000601074:sappanone A; D009569:Nitric Oxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D015232:Dinoprostone
keywords: Anti-inflammation; Heme oxygenase-1; Homoisoflavonoids; NF-κB; Nrf2; Sappanone A