Catalpol ameliorates intervertebral disc degeneration by suppressing NP cell Pyroptosis via the NF-ĸB pathway

Intervertebral disc degeneration (IDD) is a prevalent degenerative disorder and a leading cause of low back pain. Catalpol (CAT) possesses recognized anti-inflammatory and antioxidant properties and shows therapeutic potential for various inflammatory diseases; however, its role in IDD remains unclear. This study aimed to investigate the protective effects of CAT against IDD and to elucidate its underlying mechanism. The study employed both in vitro and in vivo experimental models. The effects of CAT on IDD progression were assessed, with a focus on nucleus pulposus (NP) cell pyroptosis. Mechanistic investigations were conducted to examine the involvement of the NF-κB/NLRP3-mediated pyroptotic pathway, including the nuclear translocation of phosphorylated P65 (p-P65). The dependence of CAT's action on this pathway was further verified through P65 overexpression experiments. CAT was demonstrated to alleviate IDD in experimental models. It exerted its protective effect by inhibiting pyroptosis in NP cells. Mechanistically, CAT blocked the nuclear translocation of p-P65, thereby suppressing the NF-κB/NLRP3-mediated pyroptotic pathway. The reversal of CAT's protective effects upon P65 overexpression confirmed that its action is dependent on this pathway. This study reveals that CAT alleviates IDD by directly targeting P65 to inhibit NP cell pyroptosis via the NF-κB/NLRP3 pathway. These findings identify CAT as a novel therapeutic candidate and provide a mechanistic insight for the treatment of intervertebral disc degeneration.