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

Wang, Lu; Huang, Chuyue; Li, Zhili; Hu, Guizhou; Jin, Qi; Fan, Zhun

doi:10.1016/j.heliyon.2023.e13290

Cited by 4 publications

(9 citation statements)

References 22 publications

(23 reference statements)

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“…Exogenous ligands of MRGPRX2 include the cationic polymer compound 48/80 (C48/80), which is commonly used in receptor functional assays, and a variety of drugs approved by the Food and Drug Administration (FDA), such as fluoroquinolones (e.g., ciprofloxacin), neuromuscular blocking agents (e.g., rocuronium, atracurium), opioids (e.g., morphine), and many others [ 4 , 9 , 28 ]. MRGPRX2 can also be activated or inhibited by other exogenous agents, such as bacterial quorum sensing proteins, insect venoms [ 3 , 29 , 30 ], or many different plant xenobiotics ( Figure 1 ) [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]; representatives of which are described in the following part of this review.…”

Section: Pathophysiological Basismentioning

confidence: 99%

“…It has many alleged biological effects, including protective activities against many types of cancer [ 105 ], antibacterial and anti-inflammatory effects [ 105 ]. Licorice extract contains a wide range of bioactive components, including flavonoids such as liquiritin, chalconoids (isoliquiritigenin and licochalcon A), and saponins (glycyrrhizic acid) ( Figure 1 ) [ 31 , 41 , 52 , 105 ]. Recent studies have proposed licorice ingredients as treatment agents for MRGPRX2-mediated anaphylactoid reactions [ 31 , 41 , 52 ].…”

Section: Traditional Chinese Medicines and Plant-derived Compoundsmentioning

confidence: 99%

“…Licorice extract contains a wide range of bioactive components, including flavonoids such as liquiritin, chalconoids (isoliquiritigenin and licochalcon A), and saponins (glycyrrhizic acid) ( Figure 1 ) [ 31 , 41 , 52 , 105 ]. Recent studies have proposed licorice ingredients as treatment agents for MRGPRX2-mediated anaphylactoid reactions [ 31 , 41 , 52 ]. In vitro studies of one of the active licorice flavonoids, liquiritin (LQ), demonstrated suppression of MC activation (intracellular Ca 2+ mobilization assay) and degranulation (β-hexosaminidase and histamine release) [ 41 ].…”

Section: Traditional Chinese Medicines and Plant-derived Compoundsmentioning

confidence: 99%

“…Recent studies have proposed licorice ingredients as treatment agents for MRGPRX2-mediated anaphylactoid reactions [ 31 , 41 , 52 ]. In vitro studies of one of the active licorice flavonoids, liquiritin (LQ), demonstrated suppression of MC activation (intracellular Ca 2+ mobilization assay) and degranulation (β-hexosaminidase and histamine release) [ 41 ]. The compound also showed an in vivo protective effect against anaphylaxis.…”

Section: Traditional Chinese Medicines and Plant-derived Compoundsmentioning

confidence: 99%

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Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

Dziadowiec,

Popiolek,

Kwitniewski

et al. 2024

JoX

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Mast cells (MCs) are immune cells that reside in tissues; particularly in the skin, and in the gastrointestinal and respiratory tracts. In recent years, there has been considerable interest in the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2), which is present on the surface of MCs and can be targeted by multiple exogenous and endogenous ligands. It is potentially implicated in non-IgE-mediated pseudoallergic reactions and inflammatory conditions such as asthma or atopic dermatitis. In this paper, we review natural products and herbal medicines that may potentially interact with MRGPRX2. They mainly belong to the classes of polyphenols, flavonoids, coumarins, and alkaloids. Representative compounds include rosmarinic acid, liquiritin from licorice extract, osthole, and sinomenine, respectively. While evidence-based medicine studies are still required, these compounds have shown diverse effects, such as antioxidant, analgesic, anti-inflammatory, or neuroprotective. However, despite potential beneficial effects, their use is also burdened with risks of fatal reactions such as anaphylaxis. The role of MRGPRX2 in these reactions is a subject of debate. This review explores the literature on xenobiotic compounds from herbal medicines that have been shown to act as MRGPRX2 ligands, and their potential clinical significance.

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Section: Pathophysiological Basismentioning

confidence: 99%

Section: Traditional Chinese Medicines and Plant-derived Compoundsmentioning

confidence: 99%

Section: Traditional Chinese Medicines and Plant-derived Compoundsmentioning

confidence: 99%

Section: Traditional Chinese Medicines and Plant-derived Compoundsmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

Dziadowiec,

Popiolek,

Kwitniewski

et al. 2024

JoX

View full text Add to dashboard Cite

show abstract

“…and treating coughs [32] and allergic reactions. [33] Furthermore, studies suggest that liquiritin is an effective anti-inflammatory and anti-damage drug. Its mechanism involves the downregulation of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6, IL-1β), while upregulating the anti-inflammatory cytokine IL-10.…”

mentioning

confidence: 99%

Liquiritin Ameliorates Painful Diabetic Neuropathy in SD Rats by Inhibiting NLRP3-MMP-9- mediated Reversal of Aquaporin-4 Polarity in The Glymphatic System

Jia,

Li,

et al. 2024

Preprint

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Despite advancements in diabetes treatment, the management of painful diabetic neuropathy (PDN) remains challenging. Our previous research indicated a significant correlation between the expression and distribution of Aquaporin-4 (AQP4) in the spinal glymphatic system and PDN. However, the potential role and mechanism of liquiritin in PDN treatment remain uncertain. This study established a rat model of PDN using a combination of low-dose streptozotocin (STZ) and a high-fat, high-sugar diet. Rats were treated with liquiritin and MCC950 (an NLRP3 inhibitor). We monitored fasting blood glucose, body weight, and mechanical allodynia periodically. The glymphatic system's clearance function was evaluated using Magnetic Resonance Imaging (MRI), and changes in proteins including NLRP3, MMP-9, and AQP4 were detected through immunofluorescence and Western blot techniques. The results indicate that after treatment, PDN rats showed improvements in all measured parameters. Consequently, liquiritin may alleviate PDN by modulating AQP4 expression through the NLRP3-MMP-9 pathway.

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Anti-Inflammatory and Immunoregulatory Effects of Xiaoqinglong Decoction on a Murine Model of Combined Allergic Rhinitis and Asthma Syndrome

Zhao,

Yan,

Wang

et al. 2024

Natural Product Communications

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Background Xiaoqinglong Decoction (XQLD) is a traditional Chinese medicine formula used for the treatment of allergic rhinitis and asthma, including combined allergic rhinitis and asthma syndrome (CARAS), due to its anti-inflammatory and anti-seizure properties. However, the pharmacological activities and the underlying molecular mechanisms of XQLD remain to be elucidated . Hence, we investigated the effects of XQLD against inflammation in an ovalbumin (OVA)-induced CARAS model in BALB/c mice. Methods BALB/c mice were sensitized by intraperitoneal injection and aerosol inhalation of OVA. XQLD or dexamethasone was administered by oral gavage prior to OVA challenge for 7 consecutive days. Specific airway resistance (sRAW) was evaluated 24 h after the final challenge with OVA. Enzyme-linked immunosorbent assay was used to measure the levels of serum inflammatory factors. The nasal mucosa and lung tissue were examined for general morphology and goblet hyperplasia using hematoxylin and eosin or periodic acid Schiff staining. Flow cytometry was employed to analyze the frequencies of helper T lymphocytes in peripheral blood. Immunohistochemistry was performed to determine the expression of transcription factors in helper T lymphocytes and γδ TCR. Results XQLD significantly ameliorated the symptoms of CARAS model mice, suppressed serum levels of interferon-γ, interleukin (IL)-2, IL-4, IL-5, IL-17, while increasing levels of IL-10, transforming growth factor-β. Epithelium impairment, cilia loss, eosinophil infiltration, and goblet cell metaplasia were significantly reduced in the nasal mucosa and lung tissue sections. XQLD restored the balance of Th1/Th2 and Th17/Treg cell frequency in peripheral blood. Furthermore, XQLD down-modulated the expression of GATA-binding protein 3 (GATA3), retinoic acid receptor-related orphan receptor γt, and γδ T cell receptor (TCR) in the nasal mucosa, along with GATA3 and γδ TCR in the lung tissue. Conclusions XQLD alleviated OVA-induced CARAS in BALB/c mice through its anti-allergic effects and modulation of the immune system.

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

Cited by 4 publications

References 22 publications

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

Modulation of the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) by Xenobiotic Compounds and Its Relevance to Human Diseases

Liquiritin Ameliorates Painful Diabetic Neuropathy in SD Rats by Inhibiting NLRP3-MMP-9- mediated Reversal of Aquaporin-4 Polarity in The Glymphatic System

Anti-Inflammatory and Immunoregulatory Effects of Xiaoqinglong Decoction on a Murine Model of Combined Allergic Rhinitis and Asthma Syndrome

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