Coix Seed Oil ameliorates synovial angiogenesis in collagen-induced arthritis rats through inhibiting HIF-1α / VEGF-A pathway via SIRT1

Abstract

Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by symmetric arthritis. Coix Seed Oil (CSO) has been shown to reduce inflammation in rheumatoid arthritis (RA). However, the CSO impact on synovial angiogenesis in RA remains unclear. Therefore, this study aimed to study the CSO inhibitory impact on RA synovial angiogenesis and elucidate the corresponding mechanisms. Methods Collagen-induced arthritis (CIA) rat model was established by male Sprague-Dawley rats and then treated with different doses of CSO for four weeks. Arthritis Index (AI), paw swelling, and weight of rats were recorded to assess their clinical symptoms. Hematoxylin and Eosin (H&E) staining, immunohistochemical, and immunofluorescence staining were performed to observe changes in synovial tissues. The serum HIF-1α and VEGF-A protein were evaluated through enzyme-linked immunosorbent assay (ELISA). The FLS was stimulated with TNF-α for developing an in vitro inflammatory model. Cytotoxicity and cell viability were measured using a CCK8 test. Wound healing and Transwell migration experiments were employed to determine FLS migratory ability, together with Immunofluorescence was utilized to assess HIF-1α nuclear translocation within FLS. The SIRT1, HIF-1α, VEGF-A, together with CD31 expression profiles were assessed through Western blot assays. The isolated aortic rings were extracted to observe the CSO inhibitory impact on angiogenesis. Results CSO inhibited angiogenesis, together with HIF-1α and VEGF-A expression within CIA rat synovial tissue. Mechanistically, CSO regulated the HIF-1α / VEGF-A pathway by mediating SIRT1 expression, exerting anti-angiogenic effects in vitro and in vivo. Conclusions This study indicated that CSO could ameliorate synovial angiogenesis in CIA rats through inhibiting HIF-1α / VEGF-A pathway via SIRT1.