Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in downregulating nuclear factor-kappa B pathway by Garcinol.
Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica fruit rind and other species. Recent studies have demonstrated that garcinol exhibited antioxidative effects in vitro. In this study, we found that garcinol inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated macrophages. Western blot analyzes and gel-shift assays revealed that garcinol strongly blocks the activation of eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B)-induced by LPS. Moreover, transient transfection experiments showed that garcinol inhibited the NF-kappa B-dependent transcriptional activity. Based on these data, we demonstrated that inhibition of LPS-induced NF-kappa B activation occurred through suppressing the phosphorylation of I kappa B alpha and p38 mitogen-activated kinase (MAPK). Garcinol also lowers the LPS-induced increase of intracellular reactive oxygen species (ROS), which contributes to the activation of NF-kappa B. The NF-kappa B signaling pathway leads to inflammatory reaction and our results suggest that garcinol suppresses the expression of iNOS in this pathway.
Liao
Chiung-Ho
CH
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 10018, Taiwan.
Sang
Shengmin
S
Liang
Yu-Chih
YC
Ho
Chi-Tang
CT
Lin
Jen-Kun
JK
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020672:I-kappa B Proteins; D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013729:Terpenes; D000072000:NF-KappaB Inhibitor alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; C054597:garcinol