title: Identification of NF-κB Inhibitors in Xuebijing injection for sepsis treatment based on bioactivity-integrated UPLC-Q/TOF.
abstract: BACKGROUND
  Inflammation plays an important role in sepsis, and NF-κB is a key mediator of inflammation. Xuebijing (XBJ) injection is a traditional Chinese medicine injection that was widely used in the treatment of sepsis in China. However, the active constituents and mechanism responsible for its actions have not been investigated experimentally.
  
  
  OBJECTIVE
  To screen the anti-inflammatory components in XBJ injection and investigate the modulation of NF-κB in the treatment of sepsis.
  
  
  METHODS
  In this study, the effect of XBJ was assessed in the cecal ligation and puncture (CLP) -induced sepsis model. Subsequently, a bioactivity-integrated ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF) assay system was established for screening potential anti-inflammatory ingredients in XBJ. Ultimately, six active ingredients were confirmed through an in vitro test.
  
  
  RESULTS
  XBJ significantly reduced the mortality rate, anal temperature and expression of TNF-α, IL-1β and IL-6 induced by CLP. Nine potential anti-inflammatory ingredients, including gallic acid, danshensu, protocatechualdehyde, hydroxysafflor yellow A, oxypaeoniflorin, paeoniflorin, safflor yellow A, senkyunolide I and benzoylpaeoniflorin, were found based on the bioactivity-integrated UPLC-Q/TOF assay system. Among these compounds, the NF-κB inhibitor activity of senkyunolide I, safflor yellow A, oxypaeoniflorin, and benzoylpaeoniflorin are first reported here.
  
  
  CONCLUSIONS
  XBJ showed significant efficacy in the treatment of sepsis induced by CLP. Multiple targets of the different components were related to these anti-inflammatory effects, which contributed to the treatment of sepsis by XBJ in a clinical setting.
authors.affiliation: College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Mengge
authors.initials: M
authors.lastname: Zhou
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Han
authors.forename: Lu
authors.initials: L
authors.lastname: Xing
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Zhao
authors.forename: Linyin
authors.initials: L
authors.lastname: Dong
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002853:Chromatography, Liquid / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; C549376:Xuebijing