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Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE.

ABSTRACT: Among traditional Chinese medicine injections, intravenous Shuang-Huang-Lian (IV-SHL) has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). The precise mechanisms of IV-SHL-induced IHRs remain ambiguous. In this study, we investigated the mechanisms of SHL injection (SHLI)-induced IHRs. Our data showed that serum total IgE and mouse mast cell protease 1 (MMCP1) levels were higher in the SHLI antiserum; however, these effects of SHLI disappeared in the antibiotic-treated mice. SHLI caused intraplantar vasopermeability and shock during the first local or systemic injection. SHLI-induced nonallergic IHRs were attributed to its intermediate fraction F2 (the extract of Lonicerae Japonicae Flos and Fructus forsythiae), and could be blocked by antagonists for histamine or C5a, rather than PAF or C3a. Eight constituents of F2 were able to directly activate C5 to promote local vasopermeability at the mg/mL level. In conclusion, SHLI-induced IHRs are not mediated by IgE. SHLI or its F2 can directly activate blood C5. Subsequently, C5a is likely to provoke histamine release from its effector cells (e.g., mast cells and basophils), indicating that histamine is a principal effector of IHRs induced by SHLI.

SUBMITTER: Gao Y

PROVIDER: S-EPMC5824823 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE.

Gao Yuan Y Hou Rui R Han Yixin Y Fei Qiaoling Q Cai Runlan R Qi Yun Y

Scientific reports 20180223 1

Among traditional Chinese medicine injections, intravenous Shuang-Huang-Lian (IV-SHL) has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). The precise mechanisms of IV-SHL-induced IHRs remain ambiguous. In this study, we investigated the mechanisms of SHL injection (SHLI)-induced IHRs. Our data showed that serum total IgE and mouse mast cell protease 1 (MMCP1) levels were higher in the SHLI antiserum; however, these effects of SHLI disappeared in the antibi ...[more]

PMID: 29476121

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Project description:BackgroundShuang Huang Lian (SHL) is a traditional Chinese medicine (TCM) formula made from Lonicerae Japonicae Flos, Forsythiae Fructus, and Scutellariae Radix. Despite the widespread use of SHL in clinical practice for treating upper respiratory tract infections (URTIs), the complete component fingerprint and the pharmacologically active components in the SHL formula remain unclear. The objective of this study was to develop an untargeted metabolomics method for component identification, quantitation, pattern recognition, and cross-comparison of various SHL preparation forms (i.e., granule, oral liquid, and tablet).MethodsUltra-high-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) together with bioinformatics were used for chemical profiling, identification, and quantitation of SHL. Multivariate data analyses such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to assess the correlations among the three SHL preparation forms and the reproducibility of the technical and biological replicates.ResultsA UHPLC-QTOF-MS/MS-based untargeted metabolomics method was developed and applied to analyze three SHL preparation forms, consisting of 178 to 216 molecular features. Among the 95 common molecular features from the three SHL preparation forms, quantitative analysis was performed using a single exogenous reference internal standard. Forty-seven of the 95 common molecular features have been identified using various databases. Among the 47 common components, there were 17 flavonoids, 7 oligopeptides, 5 terpenoids, 2 glycosides, 2 cyclohexanecarboxylic acids, 2 spiro compounds, 2 lipids, 2 glycosylglycerol derivatives, and 8 various compounds such as alkyl caffeate ester, aromatic ketone, benzaldehyde, benzodioxole, benzofuran, chalcone, hydroxycoumarin, and purine nucleoside. Five of the 47 common components were designated by the Chinese Pharmacopoeia as the quality markers of medicinal plants of SHL, and 15 were previously reported to have pharmacological activities. Distinct patterns of the three SHL preparation forms were observed in the PCA and PLS-DA plots.ConclusionsThe developed method is reliable and reproducible, which is useful for the profiling, component identification, quantitation, quality assessment of various SHL preparation forms and may apply to the analysis of other TCM formulas.

Project description:Huang-Lian-Jie-Du Decoction (HLJDD) is a "Fangji" made up of well-designed Chinese herb array and widely used to treat ischemic stroke. Here we aimed to investigate pharmacological mechanism by introducing an inter-module analysis to identify an overarching view of target profile and action mode of HLJDD. Stroke-related genes were obtained from OMIM (Online Mendelian Inheritance in Man). And the potential target proteins of HLJDD were identified according to TCMsp (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform). The two sets of molecules related to stroke and HLJDD were respectively imported into STRING database to construct the stroke network and HLJDD network, which were dissected into modules through MCODE, respectively. We analyzed the inter-module connectivity by quantify "coupling score" (CS) between HLJDD-modules (H-modules) and stroke-modules (S-module) to explore the pharmacological acting pattern of HLJDD on stroke. A total of 267 stroke-related proteins and 15 S-modules, 335 HLJDD putative targeting proteins, and 13 H-modules were identified, respectively. HLJDD directly targeted 28 proteins in stroke network, majority (16, 57.14%) of which were in S-modules 1 and 4. According to the modular map based on inter-module CS analysis, H-modules 1, 2, and 8 densely connected with S-modules 1, 3, and 4 to constitute a module-to-module bridgeness, and the enriched pathways of this bridgeness with top significance were TNF signaling pathway, HIF signaling pathway, and PI3K-Akt signaling pathway. Furthermore, through this bridgeness, H-modules 2 and 4 cooperatively work together to regulate mitochondrial apoptosis against the ischemia injury. Finally, the core protein in H-module 4 account for mitochondrial apoptosis was validated by an in vivo experiment. This study has developed an integrative approach by inter-modular analysis for elucidating the "shotgun-like" pharmacological mechanism of HLJDD for stroke.

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Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE.

Publications

Shuang-Huang-Lian injection induces an immediate hypersensitivity reaction via C5a but not IgE.

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