Monascus-fermented metabolite monascin suppresses inflammation via PPAR-γ regulation and JNK inactivation in THP-1 monocytes |
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Authors: | Wei-Hsuan Hsu Bao-Hong LeeTe-Han Liao Ya-Wen HsuTzu-Ming Pan |
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Institution: | Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan |
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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 E2 (PGE2) 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 NH2-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. |
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Keywords: | COX-2 cyclooxygenase-2 DMSO dimethyl sulfoxide EDTA ethylenediaminetetraacetic acid ELISA enzyme-linked immunosorbent assay ERK extracellular signal-regulated kinase FBS fetal bovine serum HPLC high-performance liquid chromatography IL-6 interleukin-6 iNOS inducible nitric oxide synthase JNK c-Jun NH2-terminal kinase MAPK mitogen-activated protein kinase MS monascin MTT 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide NO nitric oxide OVA ovalbumin PGE2 prostaglandin E2 PMSF phenylmethylsulfonyl fluoride PPAR-α peroxisome proliferator activated receptor-alpha PPAR-γ peroxisome proliferator activated receptor-gamma SDS sodium dodecyl sulfate TLC thin layer chromatography TNF-α tumor necrosis factor-α |
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