Abstract
Kadsura heteroclita (Roxb) Craib also named Xuetong in Tujia ethnomedicine in China, has been traditionally employed in rheumatoid arthritis (RA) treatment. Our preceding investigations have elucidated that Xuetongsu (XTS), a triterpenoid compound predominant in Xuetong, showed excellent anti-RA-fibroblast-like synoviocytes (RAFLS) proliferation effect. However, XTS belongs to the trace components of the Xuetong plant, this poses certain limitations to the research. In this study, we designed a method that enhanced the extraction yield of XTS and explored the mechanism of its treatment of RA in inhibiting RAFLS cell proliferation and migration. The results displayed that XTS reduced RAFLS cell proliferation, with an IC50 value of 4.68±0.65 μM. A series of experimental techniques were utilized to show that XTS induce apoptosis in RAFLS cells at concentrations ranging from 4.5 to 18 μM, including wound healing assays, flow cytometry, and Western blot analysis. Moreover, XTS at dosages of 0.42-0.84 mg/kg markedly attenuated paw swelling and synovial hyperplasia in arthritic rats, primarily through the inhibition of RAFLS migration and promotion of RAFLS apoptosis via High mobility group box 1 (HMGB-1)/Matrix metalloproteinase-9 (MMP-9) signaling pathway and Bcl-2/Bax/Caspase-3 signaling pathway, respectively.