title: Pleurotus giganteus (Berk. Karun & Hyde), the giant oyster mushroom inhibits NO production in LPS/H2O2stimulated RAW 264.7 cells via STAT 3 and COX-2 pathways.
abstract: BACKGROUND
  Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H2O2)-induced inflammation on RAW 264.7 macrophages was investigated.
  
  
  METHODS
  The effect of EPG on nitric oxide (NO) production as an indicator of inflammation in RAW 264.7 macrophages was estimated based on Griess reaction that measures nitrite level. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NF-kB activating protein (NKAP), signal transducer and activator of transcription 3 protein (STAT 3) and glutathione peroxidase (GPx) genes were assessed using real time reverse transcription polymerase chain reaction (RT-PCR) approach.
  
  
  RESULTS
  EPG (10 μg/ml) showed the highest reduction in the LPS-induced NO production in RAW 264.7 macrophages and significantly suppressed (p < 0.05) the expression iNOS, STAT 3 and COX-2. There was a significant increase (p < 0.05) in combination of LPS and H2O2- induced iNOS production when compared to the LPS-induced iNOS production in RAW 264.7 macrophages and this concurred with the NO production which was attenuated by EPG at 10 μg/ml. A significant (p < 0.05) down regulation was observed in the combination of LPS and H2O2-induced iNOS and GPx expression by EPG.
  
  
  CONCLUSIONS
  Our data suggest that the anti-inflammatory activity of EPG is mediated via the suppression of the STAT 3 and COX-2 pathways and can serve as potential endogenous antioxidant stimulant.
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.|Mushroom Research Centre, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Asweni
authors.initials: A
authors.lastname: Baskaran
authors.affiliation: Mushroom Research Centre, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.|Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Kek Heng
authors.initials: KH
authors.lastname: Chua
authors.affiliation: Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.|Mushroom Research Centre, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Vikineswary
authors.initials: V
authors.lastname: Sabaratnam
authors.affiliation: Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Mani
authors.initials: M
authors.lastname: Ravishankar Ram
authors.affiliation: Mushroom Research Centre, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia. umah@um.edu.my.|Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. umah@um.edu.my.
authors.forename: Umah Rani
authors.initials: UR
authors.lastname: Kuppusamy
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001685:Biological Factors / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020076:Pleurotus / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D001685:Biological Factors; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: COX-2; Lipopolysaccharide; Macrophage; Mushroom; NO production; Pleurotus giganteus; STAT 3; anti-inflammation