title: Identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in Chinese medicinal preparation Fuzilizhong pills using UPLC with quadrupole time-of-flight MS.
abstract: BACKGROUND
  Fuzilizhong Pills (FZLZ), a modified form of a famous traditional Chinese medicine (TCM) Lizhong Wan in Treatise on Febrile Diseases and consisting of Panax ginseng C.A.Mey. (Ren Shen), Aconitum carmichaelii Debx. (Fu Zi, Zhi), Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. (Gan Cao), Atractylodes macrocephala Koidz. (Bai Zhu) and Zingiber offcinale Rosc. (Gan Jiang), show strong clinical therapeutic effects for dyspnea and pulmonary oedema. However, the bioactive compounds are still unclear. In this study, FZLZ was analysed using a rapid detection method to identify its anti-inflammatory and spasmolytic constituents.
  
  
  OBJECTIVE
  To develop a simple screening method to detect the anti-inflammatory and spasmolytic constituents of FZLZ.
  
  
  METHODS
  Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry combined with dual-bioactive (NF-κB and β2 -adrenergic receptor) luciferase reporter assay systems was employed.
  
  
  RESULTS
  Two β2 -adrenergic receptor agonists (salsolinol and higeramine) and three terpenoidal analogues of NF-κB inhibitors such as ginsenosides derivatives, triperpenoids derivatives and diester-diterpenoid aconitum alkaloid derivatives were characterised. Mesaconitine, flaconitine, ginsenosides Rb2, Rf, Rg2, F1 and Ro were considered to be new NF-κB inhibitors. Furthermore, IL-8 detection by enzyme linked immunosorbent assay confirmed the anti-inflammatory effects of the potential NF-κB inhibitors.
  
  
  CONCLUSIONS
  Compared with conventional fingerprints, activity-integrated fingerprints that contain both chemical and bioactive details offer a more comprehensive understanding of the chemical composition of plant materials. This strategy clearly demonstrated that dual bioactivity-integrated fingerprinting is a powerful tool for the improved screening and identification of potential dual-target lead compounds in complex herbal medicines.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), College of Pharmacy, Tianjin Medical University, 300070, Tianjin, China.
authors.forename: Linyi
authors.initials: L
authors.lastname: Dong
authors.forename: Binfeng
authors.initials: B
authors.lastname: Cheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Hongquan
authors.initials: H
authors.lastname: Duan
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
mesh_terms: D031841:Aconitum / Q000737:chemistry; D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017930:Genes, Reporter; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D008156:Luciferases; D013058:Mass Spectrometry / Q000379:methods*; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005894:Panax / Q000737:chemistry; D013997:Time Factors
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D008156:Luciferases
keywords: Dual-bioactivity-integrated fingerprinting; Fuzilizhong pills; UPLC-QTOF/MS/MS; nuclear factor-κB inhibitors; β2 adrenergic receptor agonists