Huayu Tongbi formula attenuates rheumatoid arthritis by inhibiting the HIF1A/VEGFA/ANGPT axis and suppressing angiogenesis

作者：Zifeng Chen, Xiang Guo, Simin Wu, Maojie Wang, Jiaqi Wu, Haifang Du, Huiming Liang, Runyue Huang, Qingchun Huang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156479 · 被引用次数：22 · 研究领域：Traditional Chinese Medicine Analysis、Angiogenesis and VEGF in Cancer、Lipid metabolism and disorders

BACKGROUND: Angiogenesis, integral to the pathogenesis of rheumatoid arthritis (RA), contributes to the advancement of synovial hyperplasia, pannus formation, and bone destruction. The precise effect of the Huayu Tongbi formula (HT), a proven traditional Chinese medicine for RA treatment, on angiogenesis remains uncertain. PURPOSE: To investigate the effects of HT on RA angiogenesis and the potential underlying molecular mechanisms. METHODS: to simulate hypoxic conditions. Human umbilical vein endothelial cells (HUVECs) were cultured with conditioned medium (CM) from RA-FLS supplemented with HT or the HIF1A inhibitor LW-6 to investigate the impact of synovial cell secretions on angiogenesis, encompassing proliferation, migration, adhesion, and lumen formation. Western blot was employed to assess protein levels of hypoxia-inducible factor 1 subunit alpha (HIF1A), vascular endothelial growth factor receptor 2 (VEGFR2), and phosphorylated VEGFR2 (p-VEGFR2). Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify VEGFA secretion, while quantitative real-time PCR (qRT‒PCR) measured mRNA expression of VEGFA, Angiopoietin 1 (ANGPT1), and ANGPT2. In vivo, a collagen-induced arthritis (CIA) model was established. Pathological changes and vessel counts were observed via hematoxylin-eosin (HE) staining, bone structure was evaluated using X-ray, mature and immature vessels were classified via immunofluorescence, and the mechanism was further verified using immunohistochemistry...