ReferenceID 5501
Inhibitory function of Shikonin on MRGPRX2-mediated pseudo-allergic reactions induced by the secretagogue
Phytomedicine
BACKGROUND: Mast cells (MCs) are crucial effectors in allergic disorders by secreting inflammatory mediators. The Mas-related G-protein-coupled receptor X2 (Mrgprx2) was shown to have a key role in IgE-independent allerg
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- Reference Id
- 5501
- Evidence Id
- 22091
- Core Evidence Id
- 22091
- Source Reference Id
- 4246
- Herb2 Reference Id
- HBREF005043
- Subject Paper Key
- HBIN030442_32032836
- Pubmed Id
- 32032836
- Doi
- 10.1016/j.phymed.2019.153149
- Paper Title
- Inhibitory function of Shikonin on MRGPRX2-mediated pseudo-allergic reactions induced by the secretagogue
- Paper Abstract
- BACKGROUND: Mast cells (MCs) are crucial effectors in allergic disorders by secreting inflammatory mediators. The Mas-related G-protein-coupled receptor X2 (Mrgprx2) was shown to have a key role in IgE-independent allergic reactions. Therefore, potential drug candidates that directly target Mrgprx2 could be used to treat pseudo-allergic diseases. Shikonin, an active ingredient derived from Lithospermum erythrorhizon Sieb. et Zucc has been used for its anti-inflammatory properties since ancient China. PURPOSE: To investigate the inhibitory effects of Shikonin on IgE-independent allergy both in vitro and in vivo, as well as the mechanism underlying its effects. METHODS/STUDY DESIGNS: The anti-anaphylactoid activity of Shikonin was evaluated in PCA and systemic anaphylaxis models, Calcium imaging was used to assess intracellular Ca2+ mobilization. The release of cytokines and chemokines was measured using enzyme immunoassay kits. Western blot analysis was conducted to investigate the molecules of PLCgamma-PKC-IP3 signaling pathway. The analytical method of surface plasmon resonance was employed to study the interaction between Shikonin and potential target protein Mrgprx2. RESULTS: Shikonin can suppress compound 48/80 (C48/80)-induced PCA, active systemic anaphylaxis, and MCs degranulation in mice in a dose-dependent manner. In addition, Shikonin reduced C48/80-induced calcium flux and suppressed LAD2 cell degranulation via PLCgamma-PKC-IP3 signaling pathway. Moreover, Shikonin was found to inhibit C48/80-induced Mrgprx2 expression in HEK cells, displaying specific interactions with the Mrgprx2 protein. CONCLUSION: Shikonin could be a potential antagonist of Mrgprx2, thereby inhibiting pseudo-allergic reactions through Ca2+ mobilization.
- Journal
- Phytomedicine
- Publish Year
- 2020
- Experiment Subject
- mouse; hek cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Pseudo-allergic Diseases; Allergic Disorders
- Paper Title Cn
- Paper Title En
- Inhibitory function of Shikonin on MRGPRX2-mediated pseudo-allergic reactions induced by the secretagogue
- Bilingual Status
- semi_complete