title: Identification of nuclear factor-κB inhibitors in the folk herb Rhizoma Menispermi via bioactivity-based ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analysis.
abstract: BACKGROUND
  Rhizoma Menispermi (RM) is the dried root of Menispermum dauricum DC, which is traditionally used to treat swelling and pain for sore throat, enteritis and rheumatic arthralgia in the clinic, but its bioactive compounds remain unclear.
  
  
  METHODS
  In this study, RM extract was administered orally to ICR mice followed by challenging with an intratracheal Pseudomonas aeruginosa suspension. Then mortality, histological features of lung, and inflammatory cytokines were evaluated. RM treatment significantly ameliorated Pseudomonas aeruginosa-induced acute lung inflammation and reduced levels of inflammatory mediators. To screen for potential anti-inflammatory constituents of the RM extract, a simple and rapid method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) coupled with a luciferase reporter assay system to detect nuclear factor-κB (NF-κB) activity was established.
  
  
  RESULTS
  Using this system, seven potential NF-κB inhibitors were detected, including sinomenine, norsinoacutin, N-norsinoacutin-β-D-glucopyranoside, 6-O-methyl-laudanosoline-13-O-glucopyranoside, magnoflorine, laurifloline and dauricinoline. Furthermore, IL-6 and IL-8 assays confirmed the anti-inflammatory effects of these potential NF-κB inhibitors, in which norsinoacutin, 6-O-methyl-laudanosoline-13-O-glucopyranoside laurifloline, dauricinoline and N-norsinoacutin-β-D-glucopyranoside were revealed as new NF-κB inhibitors.
  
  
  CONCLUSIONS
  This method of UPLC-Q/TOF coupled with the luciferase reporter assay system was initially applied to the study of RM and was demonstrated to represent a simple, rapid and practical approach to screen for anti-inflammatory compounds. This study provided useful results for further investigation on the anti-inflammatory mechanism of RM.
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.forename: Mengge
authors.initials: M
authors.lastname: Zhou
authors.forename: Xuhui
authors.initials: X
authors.lastname: Ying
authors.forename: Binfeng
authors.initials: B
authors.lastname: Cheng
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China. houyy@nankai.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D057809:HEK293 Cells; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D031603:Menispermum / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011014:Pneumonia / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B