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
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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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