title: Monascus-fermented metabolite monascin suppresses inflammation via PPAR-γ regulation and JNK inactivation in THP-1 monocytes.
abstract: Fermentation products of the fungus Monascus offer valuable therapeutic benefits and have been used extensively for centuries in Asia. The aim of this study is to investigate the inhibitory effect of the Monascus-fermented metabolite monascin (MS) on the molecular mechanism of ovalbumin (OVA)-induced inflammation in the human THP-1 monocyte cell line. We found that 1, 5, and 25 μM of MS significantly attenuated several proinflammatory mediators, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression as well as nitric oxide (NO) and prostaglandin E(2) (PGE(2)) formation caused by OVA stimulation. Further, 5 and 25 μM of MS significantly reduced the generation of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) at both the protein and mRNA levels. MS (5 and 25 μM) decreased OVA-induced phosphorylation of mitogen-activated protein kinase (MAPK) c-Jun NH(2)-terminal kinase (JNK), but not that of extracellular signal-regulated kinase (ERK) or p38 kinase. We used the peroxisome proliferator activated receptor-γ (PPAR-γ) antagonist GW9662 to show that MS inhibit JNK phosphorylation through increased expression of PPAR-γ. Thus, the metabolites from Monascus fermentation may serve as a dietary source of anti-inflammatory agents.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan.
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Lee
authors.forename: Te-Han
authors.initials: TH
authors.lastname: Liao
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsu
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D005285:Fermentation; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032741:Monascus / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010047:Ovalbumin / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D017931:DNA Primers; D006575:Heterocyclic Compounds, 3-Ring; D047495:PPAR gamma; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C517880:monascin