Yang et al investigatedPsoralidin a coumestan derivative iso

Yang et al. investigatedPsoralidin 39, a coumestan derivative isolated from the seed of Psoralea corylifolia, regarding its effects on IR-induced pulmonary inflammation. Psoralidin 39 inhibited the IR-induced COX- 2 expression and PGE(2) production through regulation of PI3K/Akt and NF-κB pathway. Also, psoralidin 39 blocked IR-induced LTB(4) production, and it was due to direct interaction of psoralidin and 5-lipoxygenase activating protein (FLAP) in 5-LOX pathway. IR-induced fibroblast migration was notably attenuated in the presence of psoralidin. Further, in vivo results from mouse lung indicate that psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1. The findings reveal a regulatory mechanism of IR-induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that psoralidin could be useful as a potential lead compound for development of a better radiopreventive agent against radiation-induced normal tissue injury [73]. Yan et al. explored Auraptene 33 isolated from Poncirus trifoliate, a traditional Chinese medicinal plant used for treating inflammation-related diseases to evaluate their activity against prostaglandins E2 (PGE2) and cyclooxygenase-2 (COX-2) on lipopolysaccharide (LPS)-stimulated RAW 264.7 GX-674 by comparing it with aspirin as a positive control group. Auraptene 33significantly inhibited the production of PGE2 on LPS-stimulated macrophage cells. The auraptene 33 treated group had a higher COX-2 mRNA expression but relatively lower COX-2 protein level which implied that auraptene 33 suppressed the post-transcriptional expression of COX- 2 protein but not the transcriptional process [74]. Bae et al. investigated the use of Heracleum (H) moellendorffii Hance-derived Dehydrogeijerin 40 and geijerin 41 on suppression of lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage cell lines, Raw 264.7 cells. Dehydrogeijerin 40 reduced nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production from LPS-stimulated Raw 264.7 cells, but on the other hand, geijerin 41 did not reduce NO production, Pre-treatment of Raw 264.7 cells with dehydrogeijerin 40 reduced the production of cyclooxygenase-2 (COX-2) and pro-inflammatory cytokine, indicating that dehydrogeijerin 40 significantly inhibits the inflammatory activity of activated macrophages [75]. Rim et al. investigated the anti-inflammatory effects of Nodakenin 42, a coumarin isolated from the roots of Angelicae gigas, by examining its in vitro inhibitory effects on inducible nitric-oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and mouse peritoneal macrophages and it’s in vivo effects on LPS-induced septic shock in mice. The results indicated that nodakenin 42 concentration-dependently inhibits iNOS and COX-2 at the protein, mRNA, and promoter binding levels, and these inhibitions cause attendant decreases in the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Furthermore, it was found that nodakenin inhibits the production and mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β induced by LPS. Molecular data reveals that nodakenin 42 suppressed the transcriptional activity and translocation of nuclear factor-κB (NF-κB) by inhibiting inhibitory κB-α degradation and IκB kinase-α/β phosphorylation, the authors concluded that nodakenin 42 down-regulates the expression of the proinflammatory iNOS, COX-2, TNF-α, IL-6, and IL-1β genes in macrophages by interfering with the activation of TRAF6, thus preventing NF-κB activation [76]. Kwon et al. reported isolation of Fraxin 43 along with three other flavanoids from the roots of Ulmus macrocarpa Hance (Ulmaceae),a traditional medicine for the treatment of inflammation, It was observed that NO production was reduced and the expressions of iNOS and COX-2 and their mRNA were inhibited by the addition of Fraxin 43 [77].