title: Pulchellamin G, an amino acid-sesquiterpene lactone, from Saussurea pulchella suppresses lipopolysaccharide-induced inflammatory responses via heme oxygenase-1 expression in murine peritoneal macrophages.
abstract: Saussurea pulchella (Asteraceae) is widely distributed in Korea and has been used in Korean folk medicine for the treatment of inflammation, hypertension, hepatitis, and arthritis. Pulchellamin G is an amino acid-sesquiterpene lactone conjugate isolated from S. pulchella. In the present study, we focused on the anti-inflammatory effect of pulchellamin G, which acts by inducing the expression of heme oxygenase (HO)-1. HO-1 plays important roles in cytoprotection since it has antioxidant, anti-inflammatory, antiproliferative, and antiapoptotic properties. Pulchellamin G inhibited the mRNA and protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric oxide (NO), and cyclooxygenase (COX)-2 and COX-derived prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. The compound also reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production and suppressed the phosphorylation and degradation of IκB-α and nuclear translocation of p65 in murine peritoneal macrophages in response to LPS stimulus. The inhibitory effects of pulchellamin G on nuclear factor kappa B (NF-κB) translocation was impaired by co-treatment of the cells with HO activity inhibitor tin protoporphyrin (SnPP). By using SnPP, we verified that the inhibitory effects of pulchellamin G on the pro-inflammatory mediators NO, PGE2, TNF-α, and IL-1β are associated with induction of HO-1 expression. Our data suggest that pulchellamin G might have potent therapeutic effects and it should be considered in the development of treatments for various inflammatory diseases.
authors.affiliation: Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Hyun-Gyu
authors.initials: HG
authors.lastname: Choi
authors.forename: Kyeong
authors.initials: K
authors.lastname: Wan Woo
authors.forename: Dae-Gil
authors.initials: DG
authors.lastname: Kang
authors.forename: Ho-Sub
authors.initials: HS
authors.lastname: Lee
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.forename: Kang
authors.initials: K
authors.lastname: Ro Lee
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D021542:Amino Acids, Neutral / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D030441:Saussurea / Q000737:chemistry*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D045789:Sesquiterpenes, Guaiane / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D021542:Amino Acids, Neutral; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D011524:Protoporphyrins; D012333:RNA, Messenger; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C587698:pulchellamin G; D004247:DNA; D051547:Heme Oxygenase-1
keywords: Anti-inflammatory effect; Heme oxygenase-1; Murine peritoneal macrophages; Pulchellamin G; Saussurea pulchella