Zheng Yi, Yi Mengyao, Jia Tao, Xia Yifan, Zhang Yuxin, Zeng Weihui, Che Delu
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Eur J Pharmacol. 2025 Sep 15;1003:177988. doi: 10.1016/j.ejphar.2025.177988. Epub 2025 Jul 22.
Rosacea is a chronic inflammatory disease characterised by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Mas-related G protein-coupled receptor X2 (MRGPRX2), suggested as a key receptor in the pathogenesis and inflammation of rosacea, is a potential therapeutic target to treat rosacea. Antibiotics are used to treat rosacea; however, drugs for targeted treatment are lacking. Few studies have investigated drugs that inhibit MRGPRX2 expression in rosacea. Neochamaejasmin B (NCB), the most abundant component in the dried roots of the toxic perennial herb Stellera chamaejasme L., exhibits various pharmacological activities, including anti-inflammatory effects. However, the pharmacological mechanism of NCB remains unclear. In this study, we investigated the effect of NCB on the inhibition of MRGPRX2 activation in an LL-37-induced rosacea mouse model. Hematoxylin and eosin staining, immunohistochemistry, and immunofluorescence staining were used to evaluate the effects of NCB on pathogenesis. Inflammatory mediators were measured using RNA sequencing and enzyme-linked immunosorbent assay. The MRGPRX2-mediated mast cell (MC) degranulation model, molecular docking, molecular dynamics simulations, and surface plasmon resonance were used to evaluate the inhibitory effect of NCB on MRGPRX2. Finally, the downstream signalling pathway of MRGPRX2 was analyzed by western blotting. NCB reduced the pathogenesis and inflammation of rosacea in vivo by inhibiting MC activation and MRGPRX2-mediated MC activation in vitro. NCB showed a strong binding affinity for MRGPRX2 and inhibited NF-κB pathway activation. Our study showed that NCB reduced the pathogenesis and inflammation of rosacea by inhibiting MRGPRX2 activation.
酒渣鼻是一种慢性炎症性疾病，其特征为面部红斑、毛细血管扩张、丘疹、脓疱和眼部表现。Mas相关G蛋白偶联受体X2（MRGPRX2）被认为是酒渣鼻发病机制和炎症中的关键受体，是治疗酒渣鼻的潜在治疗靶点。抗生素用于治疗酒渣鼻；然而，缺乏靶向治疗药物。很少有研究调查抑制酒渣鼻中MRGPRX2表达的药物。新狼毒素B（NCB）是有毒多年生草本植物瑞香狼毒干燥根中含量最丰富的成分，具有多种药理活性，包括抗炎作用。然而，NCB的药理机制仍不清楚。在本研究中，我们在LL-37诱导的酒渣鼻小鼠模型中研究了NCB对MRGPRX2激活的抑制作用。采用苏木精-伊红染色、免疫组织化学和免疫荧光染色来评估NCB对发病机制的影响。使用RNA测序和酶联免疫吸附测定法测量炎症介质。采用MRGPRX2介导的肥大细胞（MC）脱颗粒模型、分子对接、分子动力学模拟和表面等离子体共振来评估NCB对MRGPRX2的抑制作用。最后，通过蛋白质免疫印迹分析MRGPRX2的下游信号通路。NCB通过抑制体内MC激活和体外MRGPRX2介导的MC激活来减轻酒渣鼻的发病机制和炎症。NCB对MRGPRX2表现出很强的结合亲和力，并抑制NF-κB通路激活。我们的研究表明，NCB通过抑制MRGPRX2激活来减轻酒渣鼻的发病机制和炎症。
