Identification of NF-κB Inhibitors in Xuebijing injection for sepsis treatment based on bioactivity-integrated UPLC-Q/TOF

Abstract

Ethnopharmacological evidence: Inflammation plays an important role in sepsis, and NF-κB is a key mediator of inflammation. Xuebijing (XBJ) injection is a traditional Chinese medicine injection that was widely used in the treatment of sepsis in China. However, the active constituents and mechanism responsible for its actions have not been investigated experimentally.

Aim of the study: To screen the anti-inflammatory components in XBJ injection and investigate the modulation of NF-κB in the treatment of sepsis.

Materials and methods: In this study, the effect of XBJ was assessed in the cecal ligation and puncture (CLP) -induced sepsis model. Subsequently, a bioactivity-integrated ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF) assay system was established for screening potential anti-inflammatory ingredients in XBJ. Ultimately, six active ingredients were confirmed through an in vitro test.

Results: XBJ significantly reduced the mortality rate, anal temperature and expression of TNF-α, IL-1β and IL-6 induced by CLP. Nine potential anti-inflammatory ingredients, including gallic acid, danshensu, protocatechualdehyde, hydroxysafflor yellow A, oxypaeoniflorin, paeoniflorin, safflor yellow A, senkyunolide I and benzoylpaeoniflorin, were found based on the bioactivity-integrated UPLC-Q/TOF assay system. Among these compounds, the NF-κB inhibitor activity of senkyunolide I, safflor yellow A, oxypaeoniflorin, and benzoylpaeoniflorin are first reported here.

Conclusions: XBJ showed significant efficacy in the treatment of sepsis induced by CLP. Multiple targets of the different components were related to these anti-inflammatory effects, which contributed to the treatment of sepsis by XBJ in a clinical setting.