Diosgenin suppresses angiogenesis via ROCK1 inhibition during anti-rheumatic therapies of Dioscorea spongiosa

Rheumatoid arthritis (RA) is the most common autoimmune disease, affecting 0.5%-1% of the total population worldwide. It is characterized by persistent inflammation and progressive injuries in multiple joints, and will eventually result in disabilities without appropriate medical interventions [ 1 ] [ 2 ]. The rhizome of Dioscorea spongiosa is used as a Chinese herbal medicine Bixie (BX) to treat RA. This study investigated the mechanism behind the anti-angiogenesis effects of BX. Adjuvant-induced arthritis (AIA) rats were orally treated with BX for 28 days. The therapeutic efficacy of BX was validated by serological indicators tests, histological and immunohistochemical observation. Metabolic changes were analysed by kits-based metabolites quantification and UPLC-MS analyses. The components in BX, fractions and blood from BX-treated rats were identified by LC-MS. Protein targets were pulled down by biotin-tagged compounds. Their interaction was tested by simulation docking, immunoprecipitation, thermal shift assays and enzyme digestion. BX extract eased inflammatory cytokines increase, synovial invasion and metabolic alteration in AIA rats. Angiogenesis in both white adipose tissues and joints were attenuated as demonstrated by reduced vessels, pathological factors and CD31 expression. BX inhibited glycolysis in HUVEC cells and impaired their angiogenetic ability. The expression of genes/proteins involved in VEGF and glycolytic pathways were down-regulated. Being an abundant compound in multiple bioactive fractions, diosgenin showed potentials in suppressing the activation of HUVEC cells. Biotin-conjugated diosgenin selectively bound to ROCK1, leading to its stabilization and phosphorylation inhibition. In conclusion, diosgenin inhibits ROCK1 and consequently suppresses angiogenesis dependent of glycolysis down-regulation. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany