研究动态
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基于网络药理学和体外实验的祛风止痛胶囊抗类风湿关节炎的潜在机制。

The Potential Mechanisms of Qufeng Zhitong Capsule against Rheumatoid Arthritis Based on Network Pharmacology and In Vitro Experiments.

发表日期:2024
作者: Haili Lin, Xiaokang Du, Yilu Wang, Chengsong Cai, Jin Gao, Haiyan Xiang, Feng Pan
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

祛风止痛胶囊(QFZTC)是一种传统中药配方,对类风湿性关节炎(RA)具有潜在的治疗功效。本研究旨在阐明 QFZTC 对 RA 的潜在作用和机制。 QFZTC 的活性化合物和靶标是从草药成分靶标 (HIT)、中药系统药理学数据库和分析平台 (TCMSP) 和中药综合数据库 (TCMID) 数据库中检索的。在 GeneCards 和 DisGeNET 数据库中搜索了 RA 相关目标。使用STRING数据库建立蛋白质-蛋白质相互作用(PPI)网络。对 hub 目标进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 富集分析。对中心靶标和活性化合物进行分子对接。采用高效液相色谱 (HPLC) 来表征 QFZTC 中的活性化合物。培养 RA 成纤维细胞样滑膜细胞 (RA-FLS),并用含 QFZTC 的血清处理,其中检测到促炎细胞因子和中枢靶标。通过细胞计数试剂盒 8 (CCK-8) 测定法测定细胞活力。 QFZTC 针对 RA 总共鉴定了 360 种活性化合物和 445 个潜在靶点。蛋白质-蛋白质相互作用 (PPI) 网络确定了五个中心靶点:白细胞介素 6 (IL6)、IL1B、VEGFA、JUN 和肿瘤坏死因子 (TNF)。 GO 和 KEGG 分析表明 MAPK 通路可能是 QFZTC 治疗 RA 的关键信号通路。分子对接表明木犀草素、山奈酚、杨梅素与TNF有良好的亲和力,并经HPLC鉴定。体外实验证实 QFZTC 抑制 RA 的细胞活力和炎症。这项研究揭示了 QFZTC 治疗 RA 的活性化合物和分子靶点。 QFZTC 是一种有前途的药物,通过抑制炎症反应来改善 RA。
Qufeng Zhitong capsule (QFZTC) is a traditional Chinese herbal formula with potential therapeutic efficacy in rheumatoid arthritis (RA). This study seeks to clarify the potential effects and mechanisms of QFZTC against RA. Active compounds and targets of QFZTC were retrieved from the Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID) databases. RA-related targets were searched on GeneCards and DisGeNET databases. Protein-protein interaction (PPI) network was established using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were performed on hub targets. Molecular docking was conducted on hub targets and active compounds. High-performance liquid chromatography (HPLC) was applied to characterize the active compounds in QFZTC. RA-fibroblast like synoviocytes (RA-FLSs) were cultured and treated by QFZTC-containing serum, in which proinflammatory cytokines and hub targets were detected. Cell viability was determined by cell counting kit-8 (CCK-8) assay. A total of 360 active compounds and 445 potential targets are identified for QFZTC against RA. Protein-protein interaction (PPI) network determined five hub targets, interleukin 6 (IL6), IL1B, VEGFA, JUN, and tumor necrosis factor (TNF). GO and KEGG analyses revealed that the MAPK pathway may be a critical signaling in QFZTC treating RA. Molecular docking showed that luteolin, kaempferol, and myricetin has good affinity with TNF, and they were identified by HPLC. In vitro experiments confirmed that QFZTC restrained the cell viability and inflammation in RA. This study revealed the active compounds and molecular targets for QFZTC treating RA. QFZTC is a promising drug and ameliorates RA by inhibiting inflammatory response.