Clematichinenoside AR alleviates rheumatoid arthritis by inhibiting synovial angiogenesis through the...

Clematichinenoside AR (CAR) is an effective monomer component of Clematis chinensis Osbeck, which has therapeutic effects on rheumatoid arthritis (RA), but its specific mechanism is still not fully elucidated.

This study elucidated whether CAR alleviated RA by inhibiting synovial angiogenesis and revealed its molecular mechanism.

Arthritis indicators and H&E staining were used to evaluate the therapeutic effects of CAR on collagen-induced arthritis (CIA) rats, and the IHC, IF, EdU-Hoechst, tunel, flow cytometry, wound healing and transwell assay were used to investigate the effects of CAR on synovial angiogenesis. The co-culture model of RA fibroblast-like synoviocytes (FLSs) and human umbilical vein endothelial cells (HUVECs) was established. Tube formation, western blot, RT-qPCR and other related methods were used to evaluate the specific mechanism of CAR.

CAR alleviated arthritis pathology and inhibited angiogenesis in CIA rats. CAR inhibited the proliferation, migration and invasion of RA FLSs, and promoted their apoptosis. Importantly, overexpression of HIF-1α inversed the inhibitory impact of CAR on the expression of HIF-1α, VEGFA, VEGFR2, and ANG2, as well as the inhibitory effects of CAR on the expression of CD31/34 and the HUVEC tube formation. Molecular docking, molecular dynamics, and experimental verification confirmed that CAR has a strong binding affinity with HIF-1α, further indicating that HIF-1α was a target of CAR for anti-angiogenesis.

CAR had a good inhibitory effect on RA, and its mechanism was inhibition of synovial angiogenesis through the HIF-1α/VEGF/ANG2 axis.