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Inhibitory function of Shikonin on MRGPRX2-mediated pseudo-allergic reactions induced by the secretagogue.
Phytomedicine ( IF 6.7 ) Pub Date : 2019-12-16 , DOI: 10.1016/j.phymed.2019.153149 Jue Wang 1 , Yongjing Zhang 2 , Chaomei Li 2 , Yuanyuan Ding 2 , Shiling Hu 2 , Hongli An 3
Phytomedicine ( IF 6.7 ) Pub Date : 2019-12-16 , DOI: 10.1016/j.phymed.2019.153149 Jue Wang 1 , Yongjing Zhang 2 , Chaomei Li 2 , Yuanyuan Ding 2 , Shiling Hu 2 , Hongli An 3
Affiliation
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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 PLCγ-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 PLCγ-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.
更新日期：2019-12-17
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