Xiao Tian, Tao Jie, Tan Jiaoyang, Zhao Zhourong, Yang Liping, Zhang Chao, Duan Xiaohua
Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.
Front Pharmacol. 2025 May 21;16:1571819. doi: 10.3389/fphar.2025.1571819. eCollection 2025.
This study investigated the mechanism of action of Pierre (FRP) in the treatment of chronic urticaria (CU) using a rat model and combinatorial analysis of network pharmacology, metabolomics, and molecular dynamics and dynamics simulation data, providing a rationale for its clinical use.
Twenty-four Sprague-Dawley rats were categorized into control, model, high-dose FRP (40 mg/kg body weight), and low-dose FRP (20 mg/kg body weight) groups. The CU model was induced by ovalbumin. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS) was used to estimate the levels of various components in FRP. The rats in different groups were evaluated for scratching behavior, histopathological changes in the skin tissues based on hematoxylin/eosin staining, and the levels of inflammatory factors and indicators of mast cell degranulation. Metabolomics, network pharmacology, molecular docking and dynamics simulation, and Western blotting were used to analyze the mechanism of action of FRP.
We identified 2,206 compounds in FRP based on UPLC/MS data analysis. Our data showed that the main active components in FRP were palmatine, jatrorrhizine, and coclaurine. FRP administration significantly reduced the scratching frequency, pathological characteristics of skin tissues, levels of inflammatory factors, and the degree of mast cell degranulation. Based on the combined analysis of metabolomics and network pharmacology data, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway was identified as the key target of FRP. Molecular docking and molecular dynamics simulation demonstrated strong and stable binding of Akt with palmatine, jatrorrhizine, and coclaurine. Western blotting confirmed that FRP increased the levels of p-Akt and p-PI3K in skin tissue within the CU model.
FRP significantly alleviated the symptoms and pathological changes of CU by modulating inflammation through upregulation of the PI3K-Akt signaling pathway.
本研究使用大鼠模型以及网络药理学、代谢组学、分子动力学和动力学模拟数据的组合分析，研究了皮埃尔（FRP）治疗慢性荨麻疹（CU）的作用机制，为其临床应用提供理论依据。
将24只Sprague-Dawley大鼠分为对照组、模型组、高剂量FRP（40mg/kg体重）组和低剂量FRP（20mg/kg体重）组。用卵清蛋白诱导CU模型。采用超高效液相色谱-串联质谱（UPLC/MS）法测定FRP中各成分含量。评估不同组大鼠的搔抓行为、苏木精/伊红染色观察皮肤组织的组织病理学变化，以及炎症因子水平和肥大细胞脱颗粒指标。采用代谢组学、网络药理学、分子对接和动力学模拟以及蛋白质免疫印迹法分析FRP的作用机制。
基于UPLC/MS数据分析，我们在FRP中鉴定出2206种化合物。我们的数据表明，FRP中的主要活性成分是巴马汀、药根碱和樟柳碱。给予FRP可显著降低搔抓频率、皮肤组织的病理特征、炎症因子水平以及肥大细胞脱颗粒程度。基于代谢组学和网络药理学数据的联合分析，磷脂酰肌醇3-激酶（PI3K）-蛋白激酶B（Akt）信号通路被确定为FRP的关键靶点。分子对接和分子动力学模拟表明，Akt与巴马汀、药根碱和樟柳碱有强烈且稳定的结合。蛋白质免疫印迹法证实，FRP可提高CU模型皮肤组织中p-Akt和p-PI3K的水平。
FRP通过上调PI3K-Akt信号通路调节炎症，显著减轻CU的症状和病理变化。
