通过网络药理学和实验验证探索佛罗里达铁线莲外敷治疗类风湿关节炎的机制

Pharmaceuticals Pub Date : 2024-07-09 DOI:10.3390/ph17070914
Ting Lei, Chang Jiang, Li Zhao, Jizhou Zhang, Qing Xiao, Yanhong Chen, Jie Zhang, Chunquan Zhou, Gong Wang, Jing Han
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引用次数: 0

摘要

佛罗里达铁线莲(CF)是中国东南部的一种民间药材,传统上用于治疗骨关节疾病。然而,其作用机制仍不清楚。本研究采用网络药理学和实验验证的方法探讨了佛甲草治疗类风湿性关节炎(RA)的机制。液相色谱-质谱法(LC-MS/MS)鉴定了50个CF的主要化合物,然后从TCMSP、ETCM、ITCM和SwissTargetPrediction数据库中获得了这些化合物的靶点。从 DisGeNET、OMIM 和 GeneCards 数据库中获得了与 RA 疾病相关的靶点,并利用维恩图获得了 99 个重叠靶点。构建并分析了蛋白质-蛋白质相互作用网络(PPI)、化合物-靶点网络(CT)和化合物-潜在靶基因-信号通路网络(CPS)。结果显示,筛选出的核心化合物为齐墩果酸、油酸、阿魏酸、咖啡酸和丁香酸。通过网络药理学分析预测的核心治疗靶点为 PTGS2 (COX-2)、MAPK1、NF-κB1、TNF 和 RELA,它们分别属于 MAPK 信号通路和 NF-κB 信号通路。动物实验表明,在二甲苯诱导的小鼠耳水肿模型中,CF 的局部应用显示出显著的抗炎活性,并对醋酸诱导的搔痒有很强的镇痛作用。此外,在大鼠佐剂性关节炎(AA)模型中,局部给药 CF 能够缓解脚趾肿胀,改善关节损伤。佐剂性关节炎引起的血清中 IL-6、COX-2、TNF-α、IL-1β 和 RF 含量升高在 CF 治疗后有所降低。Western印迹检测显示,CF可调节ERK和NF-κB通路。这些结果为局部应用CF治疗RA提供了新的视角。
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Exploring the Mechanism of Topical Application of Clematis Florida in the Treatment of Rheumatoid Arthritis through Network Pharmacology and Experimental Validation
Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of its action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography–mass spectrometry (LC-MS/MS) identified 50 main compounds of CF; then, their targets were obtained from TCMSP, ETCM, ITCM, and SwissTargetPrediction databases. RA disease-related targets were obtained from DisGeNET, OMIM, and GeneCards databases, and 99 overlapped targets were obtained using a Venn diagram. The protein–protein interaction network (PPI), the compound–target network (CT), and the compound–potential target genes–signaling pathways network (CPS) were constructed and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. The core therapeutic targets were predicted via network pharmacology analysis as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, and RELA, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in a mouse model of xylene-induced ear edema and had strong analgesic effect on acetic acid-induced writhing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF was able to alleviate toe swelling and ameliorate joint damage. The elevated serum content levels of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may regulate the ERK and NF-κB pathway. The results provide a new perspective for the topical application of CF for treatment of RA.
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