Achyranthoside D attenuates chondrocyte pyroptosis and inflammation in osteoarthritis via NLRP3

Osteoarthritis (OA) is an age-associated chronic degenerative joint disorder characterized by inflammation and cartilage degeneration. The NLRP3 inflammasome has been implicated in various inflammatory and age-related diseases. Achyranthes bidentata Blume (A. bidentata) is an herbal medicine commonly used for OA treatment. Achyranthoside D (AD) is a glucuronide saponin isolated from Achyranthes bidentata. However, the regulatory mechanism of AD in OA requires further elucidation. This study aimed to verify the therapeutic effect of AD on OA and identify the underlying mechanism for retarding OA progression. Anterior cruciate ligament transection (ACLT) was performed to construct an OA model. Chondrocytes induced with 5 µg/mL LPS were used for the in vitro study. Histomorphological differences were assessed using Safranin O-fast green staining. Cell viability/pyroptosis and inflammatory factor levels were analyzed using the MTT assay, flow cytometry, and ELISA. Western blotting was used to detect NLRP3-related inflammation and pyroptosis markers in chondrocytes or rat cartilage tissues. AD protected against cartilage destruction, chondrocyte pyroptosis, and inflammation in OA rats. Moreover, LPS-induced NLRP3-related inflammation and pyroptosis markers in chondrocytes were blocked by an NLRP3 inhibitor (MCC950) or AD in a dose-dependent manner. MCC950 or AD also attenuated the inflammatory response and increased cell viability in LPS-induced chondrocytes. AD attenuated OA by decreasing cartilage degradation and suppressing the inflammatory response and chondrocyte pyroptosis through inhibition of NLRP3 inflammasome activation, which may represent a promising therapeutic option for OA.

The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01077-6.