title: Microfractionation bioactivity-based ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in an alkaloidal extract of the folk herb Alstonia scholaris.
abstract: Traditional Chinese medicines (TCMs) are generally considered complementary or alternative remedies in most Western countries. The constituents of TCMs are hard to define, and their efficacy is difficult to appraise. Thus, the development of suitable methods for evaluating the relationship between bioactivity and the chemical makeup of complex TCM mixtures remains a great challenge. In the present work, the bioactivity-integrated fingerprints of alkaloidal leaf extracts of Alstonia scholaris, a folk medicinal herb for chronic respiratory diseases, were established by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF). This method was coupled with two dual-luciferase reporter assay systems to show nuclear factor-κB (NF-κB) inhibition and β(2) adrenergic receptor (β(2)AR) activation. Using UPLC-Q/TOF, 18 potential candidates were identified according to unique mass spectrometric fragmentation. After in vitro biological evaluation, several indole alkaloids with anti-inflammatory and anti-asthmatic properties were found, including akuammidine, (E)-alstoscholarine, and (Z)-alstoscholarine. Compared with conventional fingerprints, the microfractionation based bioactivity-integrated fingerprints that contain both chemical and bioactivity details offer a more comprehensive understanding of the chemical makeup 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: College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.forename: Xuelin
authors.initials: X
authors.lastname: Cao
authors.forename: Liqiang
authors.initials: L
authors.lastname: Wang
authors.forename: Binfeng
authors.initials: B
authors.lastname: Cheng
authors.forename: Linyi
authors.initials: L
authors.lastname: Dong
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Luo
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000032:analysis*; D031051:Alstonia / Q000737:chemistry*; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D026121:Indole Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013058:Mass Spectrometry / Q000379:methods; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D026121:Indole Alkaloids; D016328:NF-kappa B; D010936:Plant Extracts