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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (6): 763-773.doi: 10.12092/j.issn.1009-2501.2025.06.005

• 基础研究 • 上一篇    下一篇

基于网络药理学、分子对接及动物实验探讨毛建茶黄酮提取物改善痛风性关节炎的作用机制

杨卫东1,王瑞麒1,王海花2,叶田香1,程生辉1,李会芳1,郝旭亮3   

  1. 1山西中医药大学中药与食品工程学院,晋中  030619,山西;2山西药科职业学院,太原  030031,山西;3山西中医药大学附属医院,太原  030024,山西
  • 收稿日期:2024-06-11 修回日期:2024-09-05 出版日期:2025-06-26 发布日期:2025-06-09
  • 通讯作者: 李会芳,女,博士,教授,硕士生导师,研究方向:中药药理与毒理研究。 E-mail: sunshine_613@163.com 郝旭亮,男,博士,教授,主任药师,硕士生导师,研究方向:中药药效物质基础及作用机制研究、中药新药及健康产品开发研究。 E-mail: hxliang-01@163.com
  • 作者简介:杨卫东,男,在读硕士研究生,研究方向:中药药理与毒理研究。 E-mail: yangweidong22@163.com
  • 基金资助:
    山西省技术创新中心项目(202104010911024);青年歧黄学者支持项目;山西省科技创新人才团队项目(重点)(202204051002028)

Flavonoid extract from Dracocephalum rupestre hance in improving gouty arthritis: study based on network pharmacology, molecular docking and animal experiment

YANG Weidong1, WANG Ruiqi1, WANG Haihua2, YE Tianxiang1, CHENG Shenghui1, LI Huifang1, HAO Xuliang3   

  1. 1College of TCM and FOOD Engineer, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, Shanxi, China; 2Shanxi Pharmaceutical Vocational College, Taiyuan 030031, Shanxi, China; 3Shanxi Academy of Traditional Chinese Medicine, Taiyuan 030024, Shanxi, China
  • Received:2024-06-11 Revised:2024-09-05 Online:2025-06-26 Published:2025-06-09

摘要:

目的:通过网络药理学、分子对接及体内动物实验,探究毛建茶黄酮提取物(Flavonoid extract from Dracocephalum rupestre hance,DRHF)治疗痛风性关节炎的作用机制。方法:从文献检索挖掘DRHF主要活性化学成分、靶点,使用Gene Cards和OMIM数据库获得痛风性关节炎疾病靶点,利用韦恩在线工具获得药物与疾病交集靶点。利用Cytoscape软件构建蛋白互作关系(PPI)等相关网络图,利用Metascape数据库对共有交集靶点进行GO及KEGG富集分析。通过Coderre法建立痛风性关节炎大鼠模型;观察大鼠踝关节肿胀度,步态行为评分,苏木素-伊红(HE)染色。ELISA法和Real-time PCR法检测网络药理学预测的关键靶点,观察DRHF对痛风性关节炎治疗作用的分子机制及关键靶点的影响。结果:经筛选共得到7个活性化合物,129个DRHF治疗痛风性关节炎的候选靶点,其中核心靶点有IL-6、IL-1β、PPARG、EGFR、RELA、TNF等,KEGG富集结果提示DRHF可能通过PI3K-Akt、TNF、IL-17等信号通路发挥作用。动物实验结果:HE染色显示各给药组滑膜组织增厚不明显,滑膜细胞增生、炎性细胞浸润的情况明显改善;与正常组比较,模型组血清TNF、IL-6、IL-1β水平显著升高(P<0.05),滑膜组织中PPARG、IL-6、RELA mRNA显著升高;与模型组比较,毛建茶黄酮提取物低剂量组(DRHF-L)(0.45 g/kg)、毛建茶黄酮提取物高剂量组(DRHF-H)(0.9 g/kg)TNF、IL-6、IL-1β水平显著降低(P<0.05);滑膜组织中PPARG、IL-6、RELA mRNA显著降低。结论:毛建茶黄酮提取物通过下调IL-6、PPARG、RELA mRNA表达,降低IL-6、IL-1β、TNF等水平,抑制IL-17/PI-3K/TNF信号通路,进而治疗痛风性关节炎。

关键词: 毛建茶黄酮提取物, 痛风性关节炎, 网络药理学, 实验验证

Abstract:

AIM: To investigate the mechanism of flavonoid extract from Dracocephalum rupestre hance (DRHF) in the treatment of gouty arthritis through network pharmacology, molecular docking and animal experiment. METHODS: Literature retrieval was used to explore the main active chemical components and targets of DRHF. Gouty arthritis disease targets were obtained using Gene Cards and OMIM databases, and drug-disease intersecting targets were obtained using Wayne online tools. protein-protein interactions (PPI) and other related network diagrams were constructed using Cytoscape software. GO and KEGG enrichment analyses were performed on the shared intersecting targets using Metascape database. A rat model of gouty arthritis was established by Coderre method; the swelling degree of ankle joint, gait behaviour scores of rats were observed, and hematoxylin-eosin (HE) staining was performed. ELISA and real-time PCR were used to detect the key targets predicted by the network pharmacology, and the effects of DRHF on the molecular mechanism and key targets of gouty arthritis were observed. RESULTS: A total of 7 active compounds and 129 candidate targets for the treatment of GA were obtained, including IL-6, IL-1β, RELA, TNF, PPARG, etc. and the KEGG enrichment results suggested that DRHF may be involved in PI3K-Akt, TNF, IL-17 and other signal transduction pathways. Animal results: HE staining showed that the thickening of synovial tissue was not obvious in each administered group, and synovial cell proliferation and inflammatory cell infiltration were significantly improved; compared with the normal group, the serum levels of TNF, IL-6, and IL-1β in the model group were significantly higher (P<0.05), and the mRNA of PPARG, IL-6 , and RELA in the synovial tissues were significantly higher; compared with the model group, the levels of TNF, IL-6, and IL-1β were significantly lower (P<0.05) in the low group of DRHF (0.45 g/kg) and high group of DRHF (0.9 g/kg), TNF, IL-6, IL-1β levels were significantly reduced (P<0.05); PPARG, IL-6 , RELA mRNA in synovial tissue were significantly reduced. CONCLUSION: DRHF inhibits IL-17/PI-3K/TNF signaling pathway by down-regulating the expression of IL-6, PPARG and RELA mRNA, decreasing the levels of IL-6, IL-1β and TNF, and then treating gouty arthritis.

Key words: Dracocephalum rupestre hance, gouty arthritis, network pharmacology, experimental validation

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