title: Bioactivity-integrated ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in Chinese medicinal preparation Chuanbeipipa dropping pills.
abstract: A simple and dual-target method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with dual-bioactive [nuclear factor-κB (NF-κB) and β2 -adrenergic receptor] luciferase reporter assay systems was developed to rapidly characterize the chemical structure of various bioactive compounds of TCM preparations. Chuanbeipipa dropping pills, a traditional Chinese medicine preparation used for the clinical therapy of chronic obstructive lung disease and cough caused by bronchial catarrh, was analyzed with this method. Potential anti-inflammatory and spasmolytic constituents were screened using NF-κB and β2 -adrenergic receptor activity luciferase reporter assay systems and simultaneously identified according to the time-of-flight mass spectrometry data. One β2-adrenergic receptor agonist (ephedrine) and two structural types of NF-κB inhibitors (platycosides derivatives and ursolic acid derivatives) were characterized. Platycodin D3 and E were considered new NF-κB inhibitors. Further cytokine and chemokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors. Compared with conventional fingerprints, activity-integrated fingerprints that contain both chemical and bioactive details offer a more comprehensive understanding of the chemical makeup of plant materials. This strategy clearly demonstrated that multiple bioactivity-integrated fingerprinting is a powerful tool for the improved screening and identification of potential multi-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, Tianjin, China.
authors.forename: Linyi
authors.initials: L
authors.lastname: Dong
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Binfeng
authors.initials: B
authors.lastname: Cheng
authors.forename: Yaoshu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014162:Transfection
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D018343:Receptors, Adrenergic, beta-2; D008156:Luciferases
keywords: Chuanbeipipa dropping pills; UPLC-Q-TOF MS/MS; multiple-bioactivity-integrated fingerprinting; nuclear factor-κB inhibitors; β2 adrenergic receptor agonists