REVIEW article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1670739
Advances in MRGPRX2-Mediated Anaphylactoid Reactions to Traditional Chinese Medicine Injections
Provisionally accepted
- 1Jiangsu University, Zhenjiang, China
- 2Zhenjiang Center for Food and Drug Supervision and Inspection, Zhenjiang, China
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Traditional Chinese medicine injections (TCMIs) play an irreplaceable role in emergency treatment because of their rapid onset and high bioavailability. However, the incidence of non-IgE-mediated anaphylactoid reactions induced by TCMIs is high, accounting for the majority of acute allergic reactions, and posing a serious threat to clinical drug safety. Previous studies have identified the human Mas-related G protein-coupled receptor X2 (MRGPRX2) as the key receptor that mediates these reactions. This review discusses the crucial role of the mast cell surface receptor MRGPRX2 in TCMI-induced anaphylactoid reactions. Regarding research methodologies, approaches utilizing CRISPR/Cas9 technology or hematopoietic stem cell transplantation to construct humanized MRGPRX2 mouse models have been summarized. These models effectively addressed the issue of false negatives caused by species variation. Furthermore, an in vitro screening system based on LAD2 cells and the HEK293 overexpression system is described. Combined with calcium influx assays and histamine release measurements, this system enables precise identification of sensitizing bioactive compounds. Clinical studies indicate that MRGPRX2 polymorphisms and racial differences can affect receptor function, potentially altering sensitivity to TCMI-induced anaphylactoid reactions. Optimization strategies have been proposed based on underlying mechanisms, including the implementation of risk-stratified precision medication regimens guided by MRGPRX2 genetic screening. In summary, elucidating MRGPRX2 mechanisms, constructing relevant models, and developing intervention strategies provides a solid scientific foundation for enhancing TCMI safety, offering insights into reducing the risk of clinical anaphylactoid reactions.
Keywords: MRGPRX2, Anaphylactoid reactions, Traditional Chinese medicine injections, Humanized mouse models, Genetic polymorphisms
Received: 23 Jul 2025; Accepted: 03 Sep 2025.
Copyright: © 2025 Zhang, Ouyang, Zhang, Yin, Gu and Wei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuan Gu, gu_yuan123@163.com
Yuan Wei, ywei@ujs.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.