Periplogenin alleviates osteoarthritis by suppressing NF-κB-mediated inflammation and apoptosis in chondrocytes

Osteoarthritis (OA), a prevalent chronic degenerative disorder among middle-aged and elderly populations, is closely linked to inflammatory responses and subsequent extracellular matrix degradation. This condition causes significant patient suffering and imposes substantial socioeconomic burdens. Current therapies primarily focus on symptomatic relief (pain reduction and functional improvement), lacking targeted approaches addressing OA's underlying pathophysiological processes, while drug-related adverse effects remain problematic. Periplogenin, a natural compound with documented anti-inflammatory and anti-tumor properties, has garnered increasing attention; however, its potential role in OA pathogenesis is unexplored. This study first investigated periplogenin's effects on primary murine chondrocytes. Utilizing multiple experimental approaches, we demonstrated that periplogenin effectively attenuates TNF-α-induced inflammation, apoptosis, and consequent metabolic imbalance in chondrocytes. Furthermore, in a murine OA model, periplogenin administration conferred protective effects in vivo, mitigating OA progression. RNA sequencing analysis suggested suppression of the NF-κB signaling pathway as the potential mechanism, which was subsequently validated through both cellular and animal-level experiments. Collectively, our findings establish that periplogenin alleviates OA by inhibiting the NF-κB pathway, thereby reducing inflammation and chondrocyte apoptosis. This study identifies periplogenin as a promising candidate and provides a novel therapeutic strategy for targeted OA intervention.