Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
10.16438/j.0513-4870.2023-0591
- VernacularTitle:基于代谢组学结合生物信息学探讨热毒宁注射液与青霉素注射液联用致类过敏反应的潜在致敏原及作用机制
- Author:
Yu-long CHEN
1
;
You ZHAI
1
;
Xiao-yan WANG
2
,
3
;
Wei-xia LI
2
,
3
;
Hui ZHANG
2
;
Ya-li WU
2
;
Liu-qing YANG
2
;
Xiao-fei CHEN
2
;
Shu-qi ZHANG
2
;
Lu NIU
2
;
Ke-ran FENG
1
;
Kun LI
1
;
Jin-fa TANG
2
,
3
;
Ming-liang ZHANG
2
Author Information
1. Henan University of Chinese Medicine, Zhengzhou 450046, China
2. Henan Province Engineering Research Center for Clinical Application, Evaluation and Transformation of Traditional Chinese Medicine, Henan Provincial Key Laboratory for Clinical Pharmacy of Traditional Chinese Medicine, Henan Province Engineering Research Center of Safety Evaluation and Risk Management of Traditional Chinese Medicine, Department of Pharmacy, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China
3. Provincial and Ministerial Co-construction Collaborative Innovation Center for Prevention and Treatment of Respiratory Diseases with Traditional Chinese Medicine of Henan University of Chinese Medicine, Zhengzhou 450046, China
- Publication Type:Research Article
- Keywords:
rug combination;
pseudo-allergic reaction;
Reduning injection;
benzylpenicillin sodium for injection;
metabolomics;
bioinformatics
- From:
Acta Pharmaceutica Sinica
2024;58(2):382-394
- CountryChina
- Language:Chinese
-
Abstract:
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.