Osteoarthritis (OA) is a prevalent degenerative pathology, however, there exists a lack of cost-effective pharmacological interventions that efficaciously inhibit its progression.
ganoderic acid A (GAA), a
triterpenoid derived from Ganoderma lucidum, possesses antiapoptotic and -inflammatory effects. Our objective was to better understand the
therapeutic effects of GAA on OA as well as to elucidate the underlying mechanisms of its action. To establish an OA cell model in vitro, chondrocytes (CHONs) were treated with
interleukin (IL)-1β. Subsequently, the investigation was conducted afterward according to the following indicators: cell viability, apoptosis,
inflammation, and extracellular matrix (ECM) degradation. Western blotting analysis (WB) was employed to assess both endoplasmic reticulum (ER) stress and
proteins associated with the
nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, based on molecular docking studies, GAA exhibits a significant binding competence to p65. OA mouse models were constructed by performing a destabilization medial meniscus (DMM) operation. Moreover, histopathology and immunohistochemistry were used to determine the GAA
therapeutic effect in reducing OA in vivo. Our findings revealed that GAA has antiapoptotic, anti-inflammatory, and anti-ECM degradation effects by inhibiting the ER stress and NF-κB axis in CHONs in vitro. Furthermore, our findings suggest that GAA may attenuate the progression of
osteoarthritis in vivo. GAA can protect CHONs by regulating apoptosis, ECM changes, and
inflammation thereby preventing OA progression. These promising results indicate that GAA may be a therapeutic agent for OA treatment.