2. Academic Validation
  3. Involvement of p38 MAPK/cPLA2 and arachidonic acid metabolic pathway in Shengmai injection-induced pseudo-allergic reactions

Involvement of p38 MAPK/cPLA2 and arachidonic acid metabolic pathway in Shengmai injection-induced pseudo-allergic reactions

  • J Ethnopharmacol. 2023 Mar 9;309:116357. doi: 10.1016/j.jep.2023.116357.
Dunfang Wang 1,  Chen Pan 2,  Jiayin Han 3,  Yong Zhao 4,  Suyan Liu 5,  Chunying Li 6,  Yan Yi 7,  Yushi Zhang 8,  Xuan Tang 9,  Aihua Liang 10
Affiliations

Affiliations

  • 1 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: wdf122644@126.com.
  • 2 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: cpan@icmm.ac.cn.
  • 3 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: jyhan@icmm.ac.cn.
  • 4 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: yzhao@icmm.ac.cn.
  • 5 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: syliu@icmm.ac.cn.
  • 6 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: cyli@icmm.ac.cn.
  • 7 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: yyi@icmm.ac.cn.
  • 8 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: yszhang@icmm.ac.cn.
  • 9 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: tangxuan052@sina.com.
  • 10 Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: ahliang@icmm.ac.cn.
PMID: 36906156 DOI: 10.1016/j.jep.2023.116357
Abstract

Ethnopharmacological relevance: Adverse reactions to traditional Chinese medicine injections involve pseudo-allergic reactions (PARs). However, in clinical practice, "immediate allergic reactions" and PARs in response to these injections are not often differentiated.

Aim of the study: This study aimed to clarify the type of reactions produced by Shengmai injections (SMI) and elucidate the possible mechanism.

Materials and methods: A mouse model was used to evaluate vascular permeability. Metabolomic and arachidonic acid metabolite (AAM) analyses were performed using UPLC-MS/MS, and the p38 MAPK/cPLA2 pathway was detected by western blotting.

Results: The first exposure to intravenous SMI rapidly and dose-dependently induced edema and exudative reactions in the ears and lungs. These reactions were not IgE-dependent and were likely to be PARs. Metabolomic analysis showed that endogenous substances were perturbed in SMI-treated mice, in which the arachidonic acid (AA) metabolic pathway was the most affected. SMI substantially increased the levels of AAMs in lung, including prostaglandins (PGs), leukotrienes (LTs), and hydroxy-eicosatetraenoic acids (HETEs). The p38 MAPK/cPLA2 signaling pathway was activated after a single SMI dose. Inhibitors of cyclooxygenase-2 and 5-lipoxygenase Enzymes reduced exudation and inflammation in the ears and lungs of mice.

Conclusion: Production of inflammatory factors that increase vascular permeability may result in SMI-induced PARs, and p38 MAPK/cPLA2 signaling pathway and downstream AA metabolic pathway are involved in the reactions.

Keywords

Arachidonic acid; Metabolomics; Pseudo-allergic reactions; Shengmai injection; Vascular leakage; p38MAPK/cPLA2 signaling pathway.

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