Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases
Abstract
1. Introduction
2. Pathophysiological Basis
2.1. Mast Cell Characteristics
2.2. Structure and Regulation of MRGPRX2 Function
2.3. Role of MRGPRX2 in MC-Driven Skin Diseases
3. Traditional Chinese Medicines and Plant-Derived Compounds
3.1. TCM Compounds in Evidence-Based Medicine and Their Potential for Use in Humans
3.2. Polyphenols
3.2.1. Salvanolic Acid C and Isosalvanolic Acid C
3.2.2. Rosmarinic Acid
3.3. Flavonoids
3.3.1. Baicalin
3.3.2. Liquiritin from Licorice Extract
3.3.3. Fisetin
3.4. Coumarins
3.4.1. Praeruptorin A
3.4.2. Osthole
3.5. Alkaloids
3.5.1. Sinomenine
3.5.2. Piperine
Compound | Experimental Model or Methods | Primary Outcome Measure | Key Conclusions about Compound Activity | References | MRGPRX2 Inhibition and/or Activation | EC50 and/or IC50 for MRGPRX2 (Experimental Model and Assay) | Cmax in Plasma |
---|---|---|---|---|---|---|---|
Salvianolic acid | Molecular docking, molecular dynamics | Inhibition of PI3K and mTOR | A candidate for in vitro experiments in breast cancer studies | [89] | Activation * [37] | EC50 = 15.70 ± 4.62 μM (MPMC, β-hexosaminidase release assay) [37] | 171.48 ± 9.42 ng/mL 1 (0.00024 μM) [158] |
Rosmarinic acid | Mouse and rat models | Behavioral tests | Antinociceptive and anti-inflammatory activity | [130] | Inhibition [72] /no effect [35,40] 2 | IC50 = 1.8 mM (MRGPRX2-HEK293 cells, retention time on CMC column) [40] IC50 cannot be calculated (MRGPRX2-HEK293 cells, intracellular Ca2+ mobilization assay) [35] | |
Carrageenan-induced pleurisy and paw edema tests in rats | Behavioral tests | Potential for anti-inflammatory and antinociceptive activity | [129] | ||||
PC12 cells | Amyloid β-induced cellular reactive oxygen species generation | A candidate for neuroprotective treatment of Alzheimer’s disease | [159] | 162.20 ± 40.20 nmol/L (0.162 mM) [160] | |||
Mouse model of cardiac fibrosis | Morphological examination, echocardiography | Promising as a therapeutic agent against cardiac fibrosis | [161] | ||||
Baicalin | Mouse model of anxiety/ depression | Depression-like behaviors | Improvement of anxiety/ depression-like behaviors | [162] | Activation * [33,133] | NA | - |
Rat model of peridontitis | Toll-like receptor expression | Potential for treatment of periodontitis | [163] | ||||
Mouse model | Tumor growth | Potential for treatment of lung cancer | [87] | ||||
Liquiritin | Rat model | Cell viability, inflammatory cytokine expression | Beneficial impact on pressure ulcers | [164] | Inhibition [41] | NA | - |
Rat model | Behavioral tests | Potential for treatment of bone cancer pain | [165] | ||||
PC12 cells | Expression of proteins involved in signalling pathway | Neuroprotective activity | [166] | ||||
Diabetic mouse model | α-glucosidase inhibition | Potential for treating diabetes | [167] | ||||
H9C2 cells | Cell viability level | Cardioprotective effect | [168] | ||||
Fisetin | Male C57bl/6 J mice | Histopathological and serological injury markers | Protection against septic acute kidney injury | [142] | Inhibition [42] | NA | - |
Prostate and lung adenocarcinoma cells | Inhibition of the PI3K/AKT and the mTOR pathways | Potential as adjuvant with chemotherapeutic drugs | [143] | ||||
Osthole | Pulmonary inflammation induced in mice | Inflammatory parameters in BAL fluid | Potential for inhibition of inflammation in chronic obstructive pulmonary disease | [169] | Inhibition [34]/activation [38] 3 | NA | - |
Mouse model | Itch–scratch response | Antipruritic activity | [170] | ||||
Mouse monocyte-macrophage cells | Inflammatory mediators’ level | Potential for treatment of ulcerative colitis | [92] | ||||
Model of middle cerebral artery occlusion in rats | Determination of the infarct area | Potential for neuroprotective therapy in ischemic stroke | [93] | ||||
Bleomycin induced pulmonary fibrosis in rats | Expression of inflammatory mediators | Beneficial effects in tested model | [171] | ||||
Cervical cancer cell lines | Cancer cell viability, proliferation, and migration and invasion | Potential as adjuvant treatment for cervical cancer | [172] | ||||
Human gastric cancer cells | Cell proliferation and apoptosis | Potential for inhibition of gastric cancer cells proliferation | [88] | ||||
Osteosarcoma cell lines | Cell viability | Potential for osteosarcoma treatment | [173] | ||||
Tumor-bearing mice | Survival days | Potential for developing antitumor drugs | [174] | ||||
Diabetic mice | PPAR activation | Potential for treatment of diabetes | [175] | ||||
Skeletal muscle cells | Expression of AMP-activated protein kinase and glucose transporter 4 | Potential for treatment of diabetes | [176] | ||||
Praeruptorin A | Mouse macrophages | Expression of NF-κB-related proteins | Potential as a drug for viral infection | [177] | Activation [38] | NA | - |
Human hepatocellular carcinoma | Migration and invasion of tested cells | Potential as a therapeutic agent in human hepatocellular carcinoma | [178] | ||||
Sinomenine | Rat neuron–glial cultures | Expression of TNF-α, prostaglandin E2, and reactive oxygen species | Potential for treatment of inflammation-mediated neuro-degenerative diseases | [179] | Activation [32,39,43,153,155] | EC50 = 2.16 µM (LAD2 cells, intracellular Ca2+ mobilization assay) [32] EC50 = 1.84 µM (MRGPRX2-HEK293 cells, intracellular Ca2+ mobilization assay) [32] EC50 = 2.77 ± 0.44 µM (MRGPRX2-HEK293 cells, intracellular Ca2+ mobilization assay) [153] EC50 = 2318 ± 314 µM (MrgprB2-HEK293 cells, intracellular Ca2+ mobilization assay) [153] | |
Rats and mice models | Behavioral tests | Analgesic effect in rodent models | [180] | 123 ± 22 ng/mL (0.00037 µM) [181] | |||
Human bladder cancer cell line | P-glycoprotein expression | A candidate for treatment of bladder cancer | [182] | ||||
Mouse model of middle cerebral artery occlusion | Brain edema, neuronal apoptosis, neurological deficiency | A candidate for stroke therapy | [183] | ||||
Microglial cells | Amyloid β-induced levels of reactive oxygen species and nitric oxide | Potential for treatment of Alzheimer’s diseases | [184] | ||||
Piperine | Cervical cancer and non-tumoral cell lines | Cell proliferation, viability, and migration | Potential as complementary treatment in cervical cancer | [185] | Inhibition [36,38] | NA | - |
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Dziadowiec, A.; Popiolek, I.; Kwitniewski, M.; Porebski, G. Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases. J. Xenobiot. 2024, 14, 380-403. https://doi.org/10.3390/jox14010024
Dziadowiec A, Popiolek I, Kwitniewski M, Porebski G. Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases. Journal of Xenobiotics. 2024; 14(1):380-403. https://doi.org/10.3390/jox14010024
Chicago/Turabian StyleDziadowiec, Alicja, Iwona Popiolek, Mateusz Kwitniewski, and Grzegorz Porebski. 2024. "Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases" Journal of Xenobiotics 14, no. 1: 380-403. https://doi.org/10.3390/jox14010024
APA StyleDziadowiec, A., Popiolek, I., Kwitniewski, M., & Porebski, G. (2024). Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases. Journal of Xenobiotics, 14(1), 380-403. https://doi.org/10.3390/jox14010024