BACKGROUND: Previous studies showed that extracts of Sambucus adnata Wall. have the ability to promote the proliferation and differentiation of osteoblasts, fracture healing, anti-inflammatory and antioxidant effects, which can effectively alleviate the development of osteoarthritis. Vascular endothelial growth factor, on the other hand, is a biomarker for the evaluation of osteoarthritis severity. OBJECTIVE: To investigate the effect and mechanism of two extracts of Sambucus adnata Wall. (methanol extract SAW-ME and dichloromethane extract SAWDCE) on angiogenesis in osteoarthritis. METHODS: (1) Rat models of osteoarthritis were established using anterior cruciate ligament transection and given SAW-ME and SAW-DCE. A sham group was set as a control. Immunohistochemistry and immunofluorescence were used to detect the changes of articular vascular endothelial growth factor A in joint tissue and vascular endothelial growth factor and “H” type blood vessels in serum of osteoarthritis rats. (2) Vascular endothelial cells EA.hy926 were used as the research object and intervened with SAW-ME and SAW-DCE. Cell proliferation was then detected by MTT assay. Vascular endothelial growth factor was used to induce EA.hy926 cells, and the model of angiogenesis was replicated. Cell scratch assay and tube formation assay were performed to study the role and mechanism. (3) EA.hy926 cells were used for transcriptome sequencing to analyze the characteristic changes of cell differential genes and related functions after SAW-DCE intervention. RESULTS AND CONCLUSION: (1) SAW-ME and SAW-DCE downregulated the expression of vascular endothelial growth factor A in the rat knee cartilage and reduced the formation of “H” type vessels in osteoarthritis rats. SAW-ME could significantly decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats (P < 0.05). SAW-DCE could also decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats, but there was no significant change. (2) Both SAW-ME and SAW-DCE significantly inhibited vascular endothelial cell migration and tube formation, and downregulated the expression of Ang1 and Tie2 proteins. (3) Transcriptome sequencing analysis found that abnormal angiogenesis in osteoarthritis was related to the PI3K/AKT signaling pathway. (4) To conclude, SAW-ME and SAW-DCE can inhibit angiogenesis in the rat model of osteoarthritis, and the mechanism may be related to the Ang1/Tie2 and PI3K/AKT signaling pathways. [ABSTRACT FROM AUTHOR]