Objective To explore the effect of total saponins of Platycodon grandiflorum on cartilage injury and Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinase (ROCK) signaling pathway in knee osteoarthritis (KOA) rats.Methods Knee joint injection of papain was used to prepare a KOA model. The rats were randomly divided into model group, glucosamine sulfate (0.2 g/kg) group, total saponins of P. grandiflorum low- and high-dose (100, 200 mg/kg) groups and total saponins of P. grandiflorum (200 mg/kg) + RhoA activator LPA (1 mg/kg) group. A sham group was also included, with 15 rats in each group. After four weeks of continuous administration, micro CT scanning was used to observe changes in knee joints of rats in each group. Hematoxylin-eosin (HE) and Safranin O-fast green staining were used to observe the pathological changes of cartilage tissue. ELISA was used to detect the levels of matrix metalloproteinase-13 (MMP-13), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in joint fluid. TUNEL staining was used to observe chondrocyte apoptosis, and transmission electron microscopy was used to observe the microstructure of chondrocytes. Western blotting was used to detect expressions of aggrecan, type II collagen (Col II), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved cystein-asparate protease-3 (cleaved Caspase-3), RhoA, ROCK1 and ROCK2 proteins in cartilage tissue. Results Compared with sham group, rats in model group showed severe pathological damage to the cartilage tissue, destruction of the ultrastructure of chondrocytes, Mankin score, osteoarthritis research society international (OARSI) score, chondrocyte apoptosis rate, levels of TNF-α, MMP-13, IL-6 in joint fluid, as well as protein expression levels of RhoA, ROCK1, ROCK2, Bax and cleaved Caspase-3 in cartilage tissue were significantly increased (P < 0.05), bone volume/total volume (BV/TV), trabecular thickness (Tb.Th) and protein expression levels of Bcl-2, aggrecan, Col-II in cartilage tissue were significantly reduced (P < 0.05). Compared with model group, glucosamine sulfate group and total saponins of P. grandiflorum groups showed reduced pathological damage to cartilage tissue, normal ultrastructure of chondrocytes, Mankin score, OARSI score, chondrocyte apoptosis rate, levels of TNF-α, MMP-13, IL-6 in joint fluid, as well as protein expression levels of RhoA, ROCK1, ROCK2, Bax and cleaved Caspase-3 in cartilage tissue were significantly decreased (P < 0.05). BV/TV, Tb.Th and protein expression levels of Bcl-2, aggrecan, Col-II in cartilage tissue were significantly increased (P < 0.05). After the combined use of RhoA activator LPA, the improvement effect of total saponins of P. grandiflorum on the above indicators was partially reversed (P < 0.05). Conclusion Total saponins of P. grandiflorum can improve cartilage damage in KOA rats by inhibiting RhoA/ROCK pathway.

total saponins of Platycodon grandiflorum  /  knee osteoarthritis  /  RhoA/ROCK signaling pathway  /  cartilage injury  /  inflammatory response