Deciphering biochemical basis of Qingkailing injection-induced anaphylaxis in a rat model by time-dependent metabolomic profiling based on metabolite polarity-oriented analysis

Abstract

Ethnopharmacological relevance: Qingkailing injection (QKLI) is prepared from eight traditional Chinese medicinal materials or their extracts, which is widely used in clinical practice to treat the upper respiratory inflammation, pneumonia, high fever and viral encephalitis, nonetheless, suffering from serious anaphylaxis.

Aim of study: This study aims to develop an integrative metabolomics approach for deciphering the biochemical basis of QKLI induced anaphylaxis (QKLI-IA).

Materials and methods: The accuracy of animal modeling, the coverage of detected metabolites and the timeliness of pathological reaction are three key factors for revealing the biochemical basis of disease with untargeted metabolomics. In this study, firstly, the allergic rats (responders) were first screened by passive cutaneous anaphylaxis experiment and then were utilized for modeling. To cover a wider range of metabolites, a large-scale untargeted metabolomics based on metabolites polarity-oriented analysis was performed using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, to evaluate the timeliness of QKLI-IA, a time-dependent metabolomic profiling including the early, mid and late anaphylaxis stages of QKLI-IA, was performed.

Results: Corresponding to early, mid and late anaphylaxis stages of QKLI-IA, 14, 9 and 4 potential biomarkers were identified, respectively. Metabolism pathway analysis revealed that QKLI-IA resulted in dynamic changes in serum amino acid, fatty acid, glycerolipid, and phospholipid metabolisms. Twenty-four metabolites were found with identical fluctuating trends across the three stages of QKLI-IA. The results indicate that the pathogenesis of QKLI-IA is closely related to arachidonic acid metabolism.

Conclusion: This research provides a methodology reference for revealing the biochemical basis of disease using metabolomic profiling and offers a new insight to understand the pathogenesis of QKLI-IA.

Keywords: Anaphylaxis; Arachidonic acid; Biomarkers; Metabolomics; Qingkailing injection.