Pulchinenoside C Attenuates the Development of Osteoarthritis by Inhibiting the PI3K/AKT/NF-κB Signalling Pathway

Osteoarthritis (OA), the most prevalent type of arthritis, is characterised by permanent damage to the articular cartilage. The progression of OA is mediated by the disruption of extracellular matrix (ECM) homeostasis and the overactivation of the inflammatory response. Herbal extracts, with their safety and multi-targeting properties, have demonstrated unique advantages in inhibiting inflammation, delaying cartilage degeneration and regulating the joint microenvironment. The PI3K/Akt signalling and NF-kB signalling pathways, two classical inflammatory signalling pathways, mediate the occurrence and development of osteoarthritis by regulating the inflammatory response. Pulchinenoside C (PC, also known as Anemoside B4), derived from Pulsatilla chinensis, contains the highest concentration of triterpenoid saponins. PC exerts definite anti-inflammatory effects. However, its ability to delay the progress of OA by regulating the classical inflammatory signalling pathway remains to be clarified. This study aimed to elucidate the mechanism through which PC prevented the progression of OA in vitro and in vivo. In vitro, PC exerted significant anti-inflammatory effects on IL-1β-induced inflammatory responses in the ATDC5 cells. Notably, PC also inhibited matrix metalloproteinase expression and successfully protected the extracellular matrix of chondrocytes. In vivo, PC prevented the development of OA in a C57BL/6 mouse model of OA caused by medial meniscus (DMM) instability by inhibiting the activation of the PI3K/Akt/NF-κB pathway. These findings suggest that PC is a potentially safe and successful therapeutic agent for OA.

PI3K/AKT/NF‐κB; cartilage degeneration; osteoarthritis; pulchinenoside C; pyroptosis.