title: Identification of NF-κB inhibitors in Qishenyiqi dropping pills for myocardial infarction treatment based on bioactivity-integrated UPLC-Q/TOF MS.
abstract: Qishenyiqi dropping pills (QSYQ) are a type of standardized cardiovascular multiherb medicine for the treatment of myocardial infarction (MI). Knowledge concerning the systemic identification of nuclear factor-kappa B (NF-κB) inhibitors of QSYQ is generally lacking. Therefore, it is necessary to establish an effective method to screen the bioactive components of NF-κB inhibition. In the present study, a rat model of coronary artery ligation was used to assess the cardioprotective effects of QSYQ. The electrocardiograms, histopathology of heart tissues and serum biochemical indicators, such as brain natriuretic peptide, cardiac troponin I and inflammatory cytokines, were measured. Subsequently, ultra-performance liquid chromatography quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF MS) combined with the NF-κB luciferase reporter assay system was applied to screen the potential anti-inflammatory compounds in QSYQ. The results revealed that the administration of QSYQ could improve heart function, ameliorate neutrophil infiltration and diminish the levels of inflammatory cytokines in MI rats. Furthermore, 22 compounds were determined to be potential NF-κB inhibitors. In conclusion, NF-κB inactivation and cytokine suppression might be the main mechanisms of QSYQ for MI treatment. The method of UPLC-Q/TOF MS combined with a bioactive human cell functional evaluation system was proved to be a simple and effective strategy for screening bioactive compounds in traditional Chinese medicine prescriptions.
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.|Department of Traditional Chinese Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, People's Republic of China.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Han
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: Mengge
authors.initials: M
authors.lastname: Zhou
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: Lu
authors.initials: L
authors.lastname: Xing
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.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: Gang
authors.initials: G
authors.lastname: Bai
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.|Department of Chemistry, Tsinghua University, Beijing, 100084, People's Republic of China.
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008516:Medicine, Chinese Traditional; D009203:Myocardial Infarction / Q000188:drug therapy*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B
keywords: NF-κB inhibition; Qishenyiqi dropping pills; UPLC-Q/TOF; anti-inflammatory; myocardial infarction