title: 3,4-Dihydroxytoluene, a metabolite of rutin, inhibits inflammatory responses in lipopolysaccharide-activated macrophages by reducing the activation of NF-κB signaling.
abstract: BACKGROUND
  Saussurea involucrata (Kar. et Kir.) (S. involucrate), is a rare traditional Chinese medicinal herb. Rutin and hispidulin as well as their metabolites are flavonoids of the flavonol type that abound in S. involucrata, which has been reported to inhibit nonoxidative advanced glycation end products which was involved in physiological inflammation. This study aims to investigate the role of 3,4-dihydroxytoluene (DHT), a metabolite of rutin, in inflammatory inhibition and its involved mechanism.
  
  
  METHODS
  This study utilized lipopolysaccharide (LPS) stimulated murine macrophage cell line RAW 264.7 as inflammatory model. The inhibitory effects of DHT were evaluated by the expression level of several inflammation markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 after LPS treatment. In addition, underlying mechanisms, the activation of mitogen-activated protein kinases (MAPKs) and NF-κB, were also investigated.
  
  
  RESULTS
  Our results showed that DHT significantly suppressed the LPS-induced production of nitric oxide (NO), iNOS, and COX-2 in a dose-dependent manner without cytotoxicity. DHT also reduced the generation of proinflammatory cytokines majorly in tumor necrosis factor (TNF)-α and minor in interleukin (IL)-1β and IL-6. In addition, LPS-stimulated I-κBα phosphorylation and degradation followed by translocation of the nuclear factor κB (NF-kB)-p65 from the cytoplasm to the nucleus were attenuated after DHT treatment.
  
  
  CONCLUSIONS
  Combined, the results suggest that DHT might exert anti-inflammatory effects in vitro in LPS stimulated RAW 264.7 macrophages and is potential in adjuvant treatment in inflammation disease.
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.forename: Chao Yuan
authors.initials: CY
authors.lastname: Yu
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Shen-Lung Road, Ilan 260, Taiwan. a221865880@yahoo.com.tw.
authors.forename: Yi-Lin Sophia
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002396:Catechols / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012431:Rutin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002396:Catechols; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; C018599:4-methylcatechol; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D012431:Rutin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases