Forsythoside A and Forsythoside B Contribute to Shuanghuanglian Injection-Induced Pseudoallergic Reactions through the RhoA/ROCK Signaling Pathway
| Autor: | Chen Pan, Jiayin Han, Dunfang Wang, Lianmei Wang, Jing Meng, Aihua Liang, Yan Yi, Chunying Li, Chenling Pan, Jingzhuo Tian, Yong Zhao, Suyan Liu, Zhong Xian, Yushi Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular RHOA Rhoa rock signaling Molecular Conformation Shuanghuanglian injection Pharmacology RhoA/ROCK signaling pathway Cell Degranulation Article Catalysis Capillary Permeability Inorganic Chemistry Mice Structure-Activity Relationship Caffeic Acids Glucosides Animals Humans Glycosides Mast Cells Physical and Theoretical Chemistry Molecular Biology Rho-associated protein kinase Spectroscopy rho-Associated Kinases Molecular Structure biology forsythoside E Chemistry Organic Chemistry Degranulation Endothelial Cells General Medicine Computer Science Applications Forsythoside A biology.protein Human umbilical vein endothelial cell Forsythoside B Signal transduction pseudo-allergic reactions rhoA GTP-Binding Protein forsythoside B Drugs Chinese Herbal Signal Transduction forsythoside A |
| Zdroj: | International Journal of Molecular Sciences Volume 20 Issue 24 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms20246266 |
| Popis: | In recent years, hypersensitivity reactions to the Shuanghuanglian injection have attracted broad attention. However, the componential chief culprits inducing the reactions and the underlying mechanisms involved have not been completely defined. In this study, we used a combination of approaches based on the mouse model, human umbilical vein endothelial cell monolayer, real-time cellular monitoring, immunoblot analysis, pharmacological inhibition, and molecular docking. We demonstrated that forsythoside A and forsythoside B contributed to Shuanghuanglian injection-induced pseudoallergic reactions through activation of the RhoA/ROCK signaling pathway. Forsythoside A and forsythoside B could trigger dose-dependent vascular leakage in mice. Moreover, forsythoside A and forsythoside B slightly elicited mast cell degranulation. Correspondingly, treatment with forsythoside A and forsythoside B disrupted the endothelial barrier and augmented the expression of GTP-RhoA, p-MYPT1, and p-MLC2 in a concentration-dependent manner. Additionally, the ROCK inhibitor effectively alleviated forsythoside A/forsythoside B-induced hyperpermeability in both the endothelial cells and mice. Similar responses were not observed in the forsythoside E-treated animals and cells. These differences may be related to the potential of the tested compounds to react with RhoA-GTP&gamma S and form stable interactions. This study innovatively revealed that some forsythosides may cause vascular leakage, and therefore, limiting their contents in injections should be considered. |
| Databáze: | OpenAIRE |
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