LC-ESI-TOF-MS-based metabolomic analysis of ginsenoside Rd-induced anaphylactoid reaction in mice

As a major adverse drug reaction associated with traditional Chinese medicine injections (TCMIs), an anaphylactoid reaction has attracted a significant amount of attention from regulatory agencies and research communities. To ensure safe and effective use of TCMIs in the clinic, it is of great importance to identify the causative chemical responsible for the anaphylactoid reaction observed. Ginsenoside Rd (Rd) is one of the main active components in several TCMIs which have been recently reported to cause an anaphylactoid reaction. In this study, the possibility of an Rd-induced anaphylactoid reaction was first evaluated using general toxicological assessments. As a result, the in vitro model showed that Rd treatment could directly induce beta-hexosaminidase release in RBL-2H3 cells through mast cell degranulation. Further in vivo studies revealed that cutaneous vascular permeability and plasma histamine levels were significantly increased in Rd-treated mice, strengthening the fact that Rd could induce an anaphylactoid reaction. Moreover, a comprehensive metabolomic approach was established to investigate the effects of an Rd-induced anaphylactoid reaction in mice using liquid chromatography-electrospray ionization-time-of-flight-mass spectrometry. Our results evinced that alterations in the metabolites related to inflammation and allergy diseases were observed during the early stage of an anaphylactoid reaction, including glycerophospholipids, corticosteroid hormones, bile acids, sterol lipids, and fatty acids, suggesting that the disturbances in lipid metabolism may be involved in the Rd-induced anaphylactoid reaction, such as glycerophospholipid and steroid hormone metabolism. Thus, Rd may be an allergenic factor inducing an anaphylactoid reaction in Rd-contained TCMIs.