title: Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection.
abstract: Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction.
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China. Electronic address: deqiangdou@126.com.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Dou
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Xiaoku
authors.initials: X
authors.lastname: Ran
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life One Road, DD port, Dalian 116600, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000633:toxicity*; D007267:Injections; D008297:Male; D055432:Metabolomics / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D011914:Rats, Inbred BN; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal
keywords: Anaphylactoid reaction; Mechanism; Metabolomics; Proteomics