Simultaneous identification of the anaphylactoid components from traditional Chinese medicine injections using rat basophilic leukemia 2H3 and laboratory of allergic disease 2 dual‐mixed/cell membrane chromatography model

Abstract

Traditional Chinese medicine (TCM) has been used for prevention and treatment of various diseases for many decades. TCM injection is a new dosage form, with incidence of anaphylactoid reactions increasing every year. In this study, the rat basophilic leukemia 2H3 (RBL-2H3) and laboratory of allergic disease 2 (LAD2) dual-mixed/CMC was established and was coupled with an HPLC-ESI-IT-TOF-MS system to identify the potential allergenic components in Haqing injection. Cinobufagin, piperine, osthole, praeruptorin A, and schizandrin A were screened from Haqing injection via this coupled system. Competitive binding assay showed piperine, praeruptorin A, and schizandrin A acting on MrgprX2 and cinobufagin and osthole act on the IgE receptor. The release of mediators of anaphylaxis results showed cinobufagin and osthole can cause anaphylactoid reactions by triggering the release of β-hexosaminidase and histamine via IgE-R. Praeruptorin A and schizandrin A could promote the release of β-hexosaminidase and histamine via MrgprX2 receptor. In summary, the dual-mixed/CMC model can significantly improve the efficiency of target component identification from a complex sample. When combined with competitive binding assay and validation of biological activities, this model enables accurate determination of the dual-target components, offering improved methods for quality control of TCM injections.

Therapeutic Potential of MRGPRX2 Inhibitors on Mast Cells

“…It also suppresses MRGPRX2 expression on the plasma membrane, and thus, MRGPRX2 is inhibited through a complex mechanism [ 153 ]. In addition, Osthole has also been reported to bind to IgE receptors, which may indicate an anti-inflammatory effect of dual action on MCs [ 154 ]. In addition, dexamethasone, a well-known anti-inflammatory drug, inhibits MC activation through downregulating Gαi and MRGPRX2 downstream signals induced by basic secretagogues [ 155 ].…”

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

“…Exogenous ligands of MRGPRX2 include the cationic polymer compound 48/80 (C48/80), which is commonly used in receptor functional assays, and a variety of drugs approved by the Food and Drug Administration (FDA), such as fluoroquinolones (e.g., ciprofloxacin), neuromuscular blocking agents (e.g., rocuronium, atracurium), opioids (e.g., morphine), and many others [ 4 , 9 , 28 ]. MRGPRX2 can also be activated or inhibited by other exogenous agents, such as bacterial quorum sensing proteins, insect venoms [ 3 , 29 , 30 ], or many different plant xenobiotics ( Figure 1 ) [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]; representatives of which are described in the following part of this review.…”

“…Praeruptorins have many beneficial physiological effects in the treatment of upper respiratory tract infections, cardiovascular, immune, and nervous system diseases [ 106 ]. One of these biological compounds is praeruptorin A, which exhibits several bioactive properties ( Table 1 ) and has been studied in the context of MC activation via MRGPRX2 [ 38 ]. A competitive binding assay showed that this compound competes with ciprofloxacin for binding to MRGPRX2, suggesting that it may interact directly with the receptor [ 38 ].…”

Application progress of immobilized biomembrane in the discovery of active compounds of natural products

“…Using multiple CMs to prepare a CM chromatographic column can reduce the aforementioned disadvantage. According to this view, Han et al proposed the double mixture/CMC model for the first time (Han et al, 2018). The rat basophilic leukemia 2H3 (RBL‐2H3) and laboratory of allergic disease 2 (LAD2) dual‐mixed/CMC was created in their investigation, and it was connected with an HPLC‐ESI‐IT‐TOF‐MS system to detect probable allergenic components in Haqing injection, and cinobufagin, piperine, osthole, praeruptorin A, and schizandrin A were screened out.…”