title: Quaternary alkaloid, pseudocoptisine isolated from tubers of Corydalis turtschaninovi inhibits LPS-induced nitric oxide, PGE(2), and pro-inflammatory cytokines production via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells.
abstract: It is well known that pro-inflammatory mediators like nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) contribute to the courses of many inflammatory diseases. In the present study, the authors investigated the anti-inflammatory effects of pseudocoptisine, a quaternary alkaloid with a benzylisoquinoline skeleton, which was isolated from the tubers of Corydalis turtschaninovii by examining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Pseudocoptisine caused dose-dependent reductions in the levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) at both protein and mRNA levels and concomitant decreases in PGE(2) and NO production. In addition, it was found that pseudocoptisine suppressed the production and mRNA expressions of inflammatory cytokines, such as, TNF-alpha and IL-6. Furthermore, molecular data revealed that pseudocoptisine inhibited the LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB). Moreover, this effect was accompanied by decreases in the phosphorylation of inhibitory kappaB (IkappaB)-alpha and in the subsequent blocking of p65 subunit of NF-kappaB translocation to the nucleus. In addition, pseudocoptisine dose-dependently inhibited the phosphorylations of ERK and p38. Taken together, these results suggest that pseudocoptisine reduces levels of the pro-inflammatory mediators, such as, iNOS, COX-2, TNF-alpha, and IL-6 through the inhibition of NF-kappaB activation via the suppression of ERK and p38 phosphorylation in RAW 264.7 cells. These findings reveal in part the molecular basis for the anti-inflammatory properties of pseudocoptisine.
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Dongdaemun-ku, Seoul 130-701, Republic of Korea.
authors: Kyung-Jin
authors: KJ
authors: Yun
authors: Ji-Sun
authors: JS
authors: Shin
authors: Jung-Hye
authors: JH
authors: Choi
authors: Nam-In
authors: NI
authors: Back
authors: Hae-Gon
authors: HG
authors: Chung
authors: Kyung-Tae
authors: KT
authors: Lee
mesh_terms: D000818:Animals; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D031311:Corydalis / Q000737:chemistry; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D035281:Plant Tubers / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry
chemical_list: D044182:Benzylisoquinolines; D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000644:Quaternary Ammonium Compounds; C526231:pseudocoptisine; D009569:Nitric Oxide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone