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Screening and identification of Caulis Sinomenii bioactive ingredients with dual‐target NF‐ κ B inhibition and β 2‐ AR agonizing activities
Author(s) -
Sun Dan,
Han Yanqi,
Wang Weiya,
Wang Zengyong,
Ma Xiaoyao,
Hou Yuanyuan,
Bai Gang
Publication year - 2016
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3761
Subject(s) - chemistry , sinomenine , virtual screening , pharmacology , receptor , nf κb , liquiritigenin , biochemistry , signal transduction , pharmacophore , medicine , alternative medicine , pathology
Caulis Sinomenii (CS) is a valuable traditional medicine in China. Its extract can act as an anti‐inflammatory agent and a vascular smooth muscle relaxant. However, the underlying mechanisms remain unknown. In this study, we developed a simple dual‐target method based on ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry combined with a dual‐target bioactive screening assay for anti‐inflammatory and antispasmodic activities to characterize the chemical structure of various bioactive compounds of CS rapidly. Seven potential NF‐ κ B inhibitors were identified, including laudanosoline‐1‐ O ‐xylopyranose, 6‐ O ‐methyl‐laudanosoline‐1‐ O ‐glucopyranoside, menisperine, sinomenine, laurifoline, magnoflorine and norsinoacutin. Furthermore, IL‐6 and IL‐8 assays confirmed the anti‐inflammatory effects of these potential NF‐ κ B inhibitors, in which laudanosoline‐1‐ O ‐ d ‐xylopyranose and menisperine were revealed as novel NF‐ κ B inhibitors. Among the seven identified alkaloids, three potential β 2 ‐adrenergic receptor agonists, including sinomenine, magnoflorine and laurifoline, were characterized using a luciferase reporter system to measure for the activity of β 2 ‐adrenergic receptor agonists. Finally, sinomenine, magnoflorine and laurifoline were identified not only as potential NF‐ κ B inhibitors but also as potential β 2 ‐adrenegic receptor agonists, which is the first time this has been reported. Molecular dynamic simulation and docking results suggest that the three dual‐bioactive constituents could not only inhibit Pseudomonas aeruginosa PAK strain‐induced inflammatory responses via a negative regulation of the Braf protein that participates in MAPK signaling pathway but also activate the β 2 ‐adrenegic receptor. These results suggest that CS extract has dual signaling activities with potential clinical application as a novel drug for asthma.