Casticin reduces rosacea-related inflammation by inhibiting mast cell activation via Mas-related G protein-coupled receptor X2.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-01-17 DOI:10.1007/s10787-025-01639-8

Tao Jia, Yifan Xia, Mengyao Yi, Xinyue Zhang, Yi Zheng, Delu Che

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引用次数: 0

Abstract

Background: Rosacea is a chronic inflammatory disease characterized by persistent erythema, papules, and pustules, mainly on the skin of the face. Rosacea is difficult to treat; therefore, identifying new treatments is crucial. Mas-related G protein-coupled receptor X2 (MRGPRX2)-mediated mast cell (MC) activation is essential in the pathogenesis of rosacea. Casticin has been shown to exert anti-inflammatory effects; however, it remains unclear whether it can inhibit MRGPRX2 in treating rosacea. This study determined the therapeutic efficacy of casticin against rosacea by inhibiting MRGPRX2-mediated MC activation.

Methods: A mouse model of LL37-induced rosacea-like dermatitis was employed. The pathological changes were evaluated using hematoxylin and eosin (H&E) staining, and MCs and CD4⁺ T cells were observed. Inflammatory mediators were analyzed using ELISA. Mouse skin lesions were collected for transcriptomic sequencing. We used an MRGPRX2-mediated MC degranulation model to evaluate the inhibitory effects of casticin in vitro. Molecular docking analysis, molecular dynamics simulations, and surface plasmon resonance evaluated the binding between casticin and MRGPRX2.

Results: Casticin attenuated the LL37-induced inflammatory phenotype and reactions in rosacea-like dermatitis. RNA-seq data showed that casticin inhibited MC activation in a mouse model of rosacea. Furthermore, casticin significantly reduced CD4 + T-cell infiltration. Moreover, casticin inhibited MC activation as an MRGPRX2 antagonist in vitro and in vivo by influencing the NF-κB signaling pathway.

Conclusion: Our study demonstrated that casticin exhibits therapeutic efficacy against rosacea by inhibiting MC activation via MRGPRX2.

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蓖麻素通过抑制肥大细胞相关G蛋白偶联受体X2激活来减少酒渣鼻相关炎症。

背景：酒渣鼻是一种慢性炎症性疾病，以持续红斑、丘疹和脓疱为特征，主要发生在面部皮肤。酒渣鼻难以治疗；因此，确定新的治疗方法至关重要。mass相关G蛋白偶联受体X2 （MRGPRX2）介导的肥大细胞（MC）激活在酒渣鼻的发病机制中至关重要。蓖麻素已被证明具有抗炎作用；然而，它是否能抑制MRGPRX2治疗酒渣鼻尚不清楚。本研究通过抑制mrgprx2介导的MC激活来确定蓖麻素对酒渣鼻的治疗效果。方法：采用ll37诱导的小鼠酒渣鼻样皮炎模型。采用苏木精和伊红（H&E）染色评价病理变化，观察MCs和CD4+ T细胞的变化。采用ELISA法分析炎症介质。收集小鼠皮肤病变进行转录组测序。我们使用mrgprx2介导的MC脱粒模型来评估蓖麻素的体外抑制作用。分子对接分析、分子动力学模拟和表面等离子体共振评估了蓖麻素与MRGPRX2的结合。结果：蓖麻素减轻了ll37诱导的酒渣鼻样皮炎的炎症表型和反应。RNA-seq数据显示，蓖麻素抑制小鼠酒渣鼻模型的MC激活。此外，蓖麻素显著降低CD4 + t细胞浸润。此外，在体外和体内，蓖麻素作为MRGPRX2拮抗剂通过影响NF-κB信号通路抑制MC的激活。结论：我们的研究表明，蓖麻素通过MRGPRX2抑制MC的激活，具有治疗酒糟鼻的疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]