Ginsenoside Compound K Inhibits Wnt/β‐Catenin Signaling and Anti‐Angiogenesis, Alleviating Joint Injury in Rats With Adjuvant Arthritis

Objective To explore the effect and mechanism of GCK on synovial angiogenesis in AA rats. Methods After establishing the rat model of adjuvant arthritis, it was divided into the AA group, the GCK group (80 mg·kg −1 ·d −1 ), and the methotrexate (MTX, 0.5 mg·kg −1 ·3d −1 ) group. Meanwhile, the normal group was set as the control. The body weight, overall score, degree of paw swelling, number of paw swellings, and arthritis index of the rats were recorded. Body weight, arthritis score, and paw swelling were measured. Knee joint blood flow was assessed via ultrasound; synovial, splenic, and arterial pathology via HE staining; CD31 expression via immunohistochemistry; and serum levels of IL‐1β, IL‐6, and VEGF via ELISA. In vitro experiments used TNF‐α to stimulate EA.hy926 cells to simulate the inflammatory environment. Scratch healing experiments, Transwell, and matrix gelation tube experiments were used to evaluate the effect of GCK on angiogenesis. The content of VEGF in the cell supernatant was detected by ELISA. The expressions of β‐catenin, GSK‐3β, p‐GSK‐3 β, cyclin D1, and VEGF proteins were detected by WB. The nuclear translocation of β‐catenin was detected by cell immunofluorescence. Result GCK significantly alleviated synovial inflammation and joint injury in AA rats, inhibited TNF‐α‐induced endothelial cell activation and inflammatory response, and suppressed Wnt/β‐catenin signaling activation. Conclusion GCK can effectively alleviate synovial inflammation and joint injury in AA rats. This effect may be related to the inhibition of Wnt/β‐catenin signaling and the reduction of synovial angiogenesis.