竹节人参总皂苷对类风湿关节炎的抗血管生成作用是通过靶向缺氧诱导因子-1α/血管内皮生长因子/血管生成素-1轴介导的。
The antiangiogenic effect of total saponins of Panax japonicus C.A. Meyer in rheumatoid arthritis is mediated by targeting the HIF-1α/VEGF/ANG-1 axis.
作者信息
Guo Xiang, Zhang Jinkai, Feng Zhitao, Ji Jinyu, Shen Xiaolan, Hou Xiaoqiang, Mei Zhigang
机构信息
Third-Grade Pharmacological Laboratory on Chinese Medicine Approved By State Administration of Traditional Chinese Medicine, College of Medicine and Health Science, China Three Gorges University, Yichang, Hubei, 443002, China; The Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, 51006, China.
Third-Grade Pharmacological Laboratory on Chinese Medicine Approved By State Administration of Traditional Chinese Medicine, College of Medicine and Health Science, China Three Gorges University, Yichang, Hubei, 443002, China.
出版信息
J Ethnopharmacol. 2024 Oct 28;333:118422. doi: 10.1016/j.jep.2024.118422. Epub 2024 Jun 3.
ETHNOPHARMACOLOGICAL RELEVANCE
Traditional Chinese herbal medicine Panax japonicus C.A. Meyer has a long history in clinical treatment of rheumatoid arthritis (RA). Total saponins of Panax japonicus C.A. Meyer (TSPJs) were extracted from the root of Panax japonicus C.A. Meyer, and its anti-rheumatism mechanism is still unclear.
AIM OF THE STUDY
To investigate whether TSPJs attenuated synovial angiogenesis in RA and explore the potential mechanisms.
MATERIALS AND METHODS
Potential TSPJs targets involving gene function were predicted by network pharmacology related databases. Bioinformatics analysis and molecular docking technology were used to predict the mechanism of TSPJs in the treatment of RA. The predicted results were validated by cell experiments and a collagen-induced arthritis (CIA) mouse model.
RESULTS
Bioinformatics analysis results showed that TSPJs may inhibit RA-related angiogenesis through the hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) pathways. In vitro, different doses of TSPJs showed a good inhibitory effect on the tube formation of EA.hy926 cells. The results of the cellular thermal shift assay indicated that TSPJs can bind to the HIF-1α, VEGFA, and angiopoietin-1 (ANG-1) proteins. In vivo, the administration of TSPJs alleviated the symptoms of CIA mice, including the arthritis index, hind paw thickness, and swollen joint count. The histological results demonstrated that TSPJs inhibited inflammation, angiogenesis, bone damage, and cartilage destruction. Furthermore, TSPJs decreased the number of vessels and the expression level of CD31. The mechanistic results revealed that TSPJs decreased the expression of HIF-1α, VEGFA, and ANG-1 in the serum or synovial tissues of CIA mice.
CONCLUSION
These results suggest that TSPJs effectively inhibit angiogenesis in RA, and the mechanism may be related to inhibiting the HIF-1α/VEGF/ANG-1 axis.
民族药理学相关性
传统中药三叶参在类风湿性关节炎（RA）的临床治疗中有着悠久的历史。三叶参总皂苷（TSPJs）从三叶参的根部提取，其抗风湿机制仍不清楚。
研究目的
研究TSPJs是否能减轻RA中的滑膜血管生成并探索潜在机制。
材料与方法
通过网络药理学相关数据库预测涉及基因功能的潜在TSPJs靶点。利用生物信息学分析和分子对接技术预测TSPJs治疗RA的机制。通过细胞实验和胶原诱导性关节炎（CIA）小鼠模型验证预测结果。
结果
生物信息学分析结果表明，TSPJs可能通过缺氧诱导因子-1（HIF-1）和血管内皮生长因子（VEGF）途径抑制RA相关的血管生成。在体外，不同剂量的TSPJs对EA.hy926细胞的管腔形成显示出良好的抑制作用。细胞热位移分析结果表明，TSPJs能与HIF-1α、VEGFA和血管生成素-1（ANG-1）蛋白结合。在体内，给予TSPJs可减轻CIA小鼠的症状，包括关节炎指数、后爪厚度和肿胀关节数。组织学结果表明，TSPJs抑制炎症、血管生成、骨损伤和软骨破坏。此外，TSPJs减少了血管数量和CD31的表达水平。机制研究结果显示，TSPJs降低了CIA小鼠血清或滑膜组织中HIF-1α、VEGFA和ANG-1的表达。
结论
这些结果表明，TSPJs能有效抑制RA中的血管生成，其机制可能与抑制HIF-1α/VEGF/ANG-1轴有关。
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