Baicalin induces Mrgprb2-dependent pseudo-allergy in mice

Wang, Jue; Zhang, Yongjing; Che, Delu; Zeng, Yingnan; Wu, Yuanyuan; Qin, Qiaohong; Wang, Nan

doi:10.1016/j.imlet.2020.07.006

Cited by 16 publications

(12 citation statements)

References 31 publications

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“…Another natural compound present in traditional Chinese medicine is baicalin, which has been reported to activate MCs via MRGPRX2 in a concentration-dependent manner. These pseudo-allergy reactions induced by baicalein were absent in MPGPRB2-knockout mice [ 116 ].…”

Section: Pharmacology Of Mas-related G Protein-coupled Receptors X 2 (Mrgprx2)mentioning

confidence: 99%

Unlocking the Non-IgE-Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2)

Kumar

Duraisamy

Chow

2021

Cells

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Mas-related G-protein coupled receptor member X2 (MRGPRX2) is a class A GPCR expressed on mast cells. Mast cells are granulated tissue-resident cells known for host cell response, allergic response, and vascular homeostasis. Immunoglobulin E receptor (FcεRI)-mediated mast cell activation is a well-studied and recognized mechanism of allergy and hypersensitivity reactions. However, non-IgE-mediated mast cell activation is less explored and is not well recognized. After decades of uncertainty, MRGPRX2 was discovered as the receptor responsible for non-IgE-mediated mast cells activation. The puzzle of non-IgE-mediated pseudo-allergic reaction is unlocked by MRGPRX2, evidenced by a plethora of reported endogenous and exogenous MRGPRX2 agonists. MRGPRX2 is exclusively expressed on mast cells and exhibits varying affinity for many molecules such as antimicrobial host defense peptides, neuropeptides, and even US Food and Drug Administration-approved drugs. The discovery of MRGPRX2 has changed our understanding of mast cell biology and filled the missing link of the underlying mechanism of drug-induced MC degranulation and pseudo-allergic reactions. These non-canonical characteristics render MRGPRX2 an intriguing player in allergic diseases. In the present article, we reviewed the emerging role of MRGPRX2 as a non-IgE-mediated mechanism of mast cell activation in pseudo-allergic reactions. We have presented an overview of mast cells, their receptors, structural insight into MRGPRX2, MRGPRX2 agonists and antagonists, the crucial role of MRGPRX2 in pseudo-allergic reactions, current challenges, and the future research direction.

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Section: Pharmacology Of Mas-related G Protein-coupled Receptors X 2 (Mrgprx2)mentioning

confidence: 99%

Unlocking the Non-IgE-Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2)

Kumar

Duraisamy

Chow

2021

Cells

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“…Other than body-produced peptides, MRGPRX2 was shown to bind with diverse externally delivered agonists such as insect venom chemical components and many drugs [ 27 ]. Therefore, MRGPRX2 inhibitors are expected to be tested in MC-related medical conditions with few effective therapeutic agents, such as postoperative pain, migraine, and drug-induced acute pseudo allergic reactions [ 28 ].…”

Section: Mast Cell Disordersmentioning

confidence: 99%

Mast Cells in the Mammalian Testis and Epididymis—Animal Models and Detection Methods

Himelreich-Perić

Katušić-Bojanac

Hohšteter

et al. 2022

IJMS

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Mast cells (MCs) are an evolutionary well-conserved type of cells, mediating and modulating allergic responses in innate immunity and tissue remodeling after chronic inflammation. Among other tissues, they inhabit both the testis and epididymis. In the testis, MCs usually appear in the interstitial compartment in humans, but not in other standard experimental models, like rats and mice. MCs seem to be responsible for testicular tissue fibrosis in different causes of infertility. Although experimental animal models follow the effect on MC activation or penetration to the interstitial tissue like in humans to some extent, there is an inconsistency in the available literature regarding experimental design, animal strain, and detection methods used. This comprehensive review offers an insight into the literature on MCs in mammalian testes and epididymides. We aimed to find the most suitable model for research on MC and offer recommendations for future experimental designs. When using in vivo animal models, tunica albuginea incorporation and standard histological assessment need to be included. Domesticated boar strains kept in modified controlled conditions exhibit the highest similarity to the MC distribution in the human testis. 3D testicular models are promising but need further fine-tuning to become a valid model for MC investigation.

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“…4B; Table 6), which demonstrated to be mitochondrial toxic. As summarized in Table 4, baicalin and rutin are the main components in SHL injection causing the anaphylactoid reaction (Wang et al 2020;Zhang et al 2017). Baicalin, also present in YZH injection, has been reported to induce kidney damage and renal brosis (Cai et al 2017).…”

Section: In Vitro Validation Of Mitochondrial Toxicity Of Identi Ed T...mentioning

confidence: 99%

A dual in vitro approach for systematic analysis of mitochondrial toxicity in traditional Chinese medicine injections

Shen

Guo

Ma³

et al. 2022

Preprint

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Background There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Objectives To establish a dual in vitro mitochondrial toxicity assay approach for systematically evaluating mitochondrial toxicity of TCM injections. Methods Using this dual in vitro approach, the effect of TCM injections exposure on ATP depletion in HepG2 cells was examined by the conventional “glucose/galactose” assay. The cytotoxicity of TCM injections on HCT116 WT and HCT116 SCO2 KO cell lines was determined by sulforhodamine B (SRB) colorimetric assay. Subsequently, mitochondrial toxicity of ingredients in identified TCM injections was validated by combining molecular docking analysis with experimental validation. Results Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in 4 TCM injections by combining molecular docking analysis with experimental validation. Conclusions Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.

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Baicalin induces Mrgprb2-dependent pseudo-allergy in mice

Cited by 16 publications

References 31 publications

Unlocking the Non-IgE-Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2)

Unlocking the Non-IgE-Mediated Pseudo-Allergic Reaction Puzzle with Mas-Related G-Protein Coupled Receptor Member X2 (MRGPRX2)

Mast Cells in the Mammalian Testis and Epididymis—Animal Models and Detection Methods

A dual in vitro approach for systematic analysis of mitochondrial toxicity in traditional Chinese medicine injections

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