Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK pathways in LPS-stimulated mouse macrophages.
We use the LPS-stimulated macrophage as a model of inflammation to investigate the anti-inflammatory effects of tomatidine and solasodine, whose structures resemble glucocorticoids. We found that tomatidine exhibited a more potent anti-inflammatory effect than solasodine. Tomatidine could decrease inducible nitric oxide synthase and cyclooxygenase-2 expression through suppression of I-kappaBalpha phosphorylation, NF-kappaB nuclear translocation and JNK activation, which in turn inhibits c-jun phosphorylation and Oct-2 expression. Here, we demonstrate that tomatidine acts as an anti-inflammatory agent by blocking NF-kappaB and JNK signaling, and may possibly be developed as a useful agent for the chemoprevention of cancer or inflammatory diseases.
Chiu
Feng-Lan
FL
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1 Section 1, Jen-ai Road, Taipei 10018, Taiwan.
Lin
Jen-Kun
JK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D004144:Diosgenin / Q000737:chemistry / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D050813:Octamer Transcription Factor-2 / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction; D012991:Solanaceous Alkaloids / Q000737:chemistry / Q000494:pharmacology; D014053:Tomatine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D050813:Octamer Transcription Factor-2; D016755:Proto-Oncogene Proteins c-jun; D012991:Solanaceous Alkaloids; D000072000:NF-KappaB Inhibitor alpha; C003677:tomatidine; D009569:Nitric Oxide; D014053:Tomatine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D004144:Diosgenin; D015232:Dinoprostone; C012037:solasodine