Dataset Information

Liquiritin inhibits MRGPRX2-mediated pseudo-allergy through the PI3K/AKT and PLCγ signaling pathways.

ABSTRACT: Liquiritin is a natural flavone with a variety of pharmacological effects derived from the medicinal food homology plant Glycyrrhiza uralensis Fisch. As a kind of lethal allergic reactions, pseudo-allergic reactions (PARs) arise from the Mas-related G protein coupled receptor X2 (MRGPRX2)-triggered fast degranulation of mast cells (MCs). In the current work, the anti-pseudo-allergy action and potential mechanisms of liquiritin were explored in vivo and in vitro. Liquiritin suppressed the calcium influx and degranulation elicited by Compound 48/80 (C48/80) in mouse peritoneal mast cells (MPMCs). In mice, liquiritin also inhibited the C48/80-elicited hind paw extravasation, as well as the elevations in TNF-α and histamine levels. Molecular docking combined with detection of HEK293T cells expressing human MRGPRX2 showed that liquiritin was a potential MRGPRX2 antagonist and inhibited PARs through the PI3K/AKT and PLCγ signaling pathways downstream of MRGPRX2. The present work opens a new avenue for the PARs management.

SUBMITTER: Wang L

PROVIDER: S-EPMC9932484 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Liquiritin inhibits MRGPRX2-mediated pseudo-allergy through the PI3K/AKT and PLCγ signaling pathways.

Wang Lu L Huang Chuyue C Li Zhili Z Hu Guizhou G Qi Jin J Fan Zhimin Z

Heliyon 20230131 2

Liquiritin is a natural flavone with a variety of pharmacological effects derived from the medicinal food homology plant Glycyrrhiza uralensis Fisch. As a kind of lethal allergic reactions, pseudo-allergic reactions (PARs) arise from the Mas-related G protein coupled receptor X2 (MRGPRX2)-triggered fast degranulation of mast cells (MCs). In the current work, the anti-pseudo-allergy action and potential mechanisms of liquiritin were explored in vivo and in vitro. Liquiritin s ...[more]

PMID: 36816265

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Project description:Glioblastoma is a high-grade glioma with poor prognosis even after surgery and standard therapy. Here, we asked whether carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, exert its anti-neoplastic effect on glioblastoma cells via PI3K/Akt/mTOR signaling. Therefore, glioblastoma cells from the lines U87 and T98G were exposed to carnosine, to the mTOR inhibitor rapamycin and to the PI3K inhibitor Ly-294,002. Pyruvate dehydrogenase kinase (PDK4) expression, known to be a target of PI3K/Akt/mTOR, and which is also affected by carnosine, was analyzed by RT-qPCR, and reporter gene assays with the human PDK4 promoter were performed. Cell viability was assessed by cell-based assays and mTOR and Akt phosphorylation by Western blotting. Rapamycin and Ly-294,002 increased PDK4 mRNA expression in both cell lines but significance was only reached in U87. Carnosine significantly increased expression in both lines. A significant combinatorial effect of carnosine was only detected in U87 when the dipeptide was combined with Ly-294,002. Reporter gene assays revealed no specific effect of carnosine on the human PDK4 promoter, whereas both inhibitors increased reporter gene expression. Rapamycin reduced phosphorylation of mTOR, and Ly-294,002 that of Akt. A significant reduction of Akt phosphorylation was observed in the presence of carnosine in U87 but not in T98G, and carnosine had no effect on mTOR phosphorylation. Cell viability as determined by ATP in cell lysates was reduced only in the presence of carnosine. We conclude that carnosine's anti-neoplastic effect is independent from PI3K/Akt/mTOR signaling. As the dipeptide reduced viability in tumor cells that do not respond to PI3K or mTOR inhibitors, it appears to be worth to further investigate the mechanisms by which carnosine exerts its anti-tumor effect and to consider it for therapy, especially as it is a naturally occurring compound that has already been used for the treatment of other diseases without indication of side-effects.

Dataset Information

Liquiritin inhibits MRGPRX2-mediated pseudo-allergy through the PI3K/AKT and PLCγ signaling pathways.

Publications

Liquiritin inhibits MRGPRX2-mediated pseudo-allergy through the PI3K/AKT and PLCγ signaling pathways.

Similar Datasets

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