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.

Bioactivity-based antioxidative components screening and evaluation in grape seed proanthocyanidin extract

“…Diverse bioactivity-integrated UPLC-Q/TOF MS analysis systems have been established in our laboratory. An analysis system coupled with the NF-jB luciferase reporter assay system has been applied successfully to the identification of NF-jB inhibitors in many types of plant extracts and multiherb medicines (Jiang et al 2014;Gao et al 2015;Han et al 2015). Recently, our UPLC-Q/TOF MS system combined with the dual-luciferase reporter assay for intracellular calcium also successfully screened out synergistic bronchodilators from a traditional Chinese medicine (Hou et al 2014).…”

Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells

“…The results demonstrated that CYT treatment decreased the levels of TNF-α, IL-1β and IL-6 in LPS-induced CMECs. An increasing number of studies have revealed that the NF-κB signaling pathway serves an important role in regulating inflammatory responses ( 16 , 24 ). NF-κB is comprised of NF-κB p50 and NF-κB p65 subunits, which are generally localized in the cytoplasm together with its inhibitor, IκB.…”