Ginsenoside-Rh2 Alleviates Pyroptosis of Nucleus Pulposus Cells by Activating Autophagy via HIF-1α to Retard the Progression of Intervertebral Disc Degeneration.

In the pathogenesis of intervertebral disc degeneration (IVDD), nucleus pulposus (NP) cell dysfunction is a pivotal factor, specifically manifested as extracellular matrix degradation, impaired autophagy, and pyroptosis. Ginsenoside-Rh2 (GRh2) possesses pharmacological activities, yet its role in IVDD remains unclear. This study used interleukin-1β (IL-1β) to mimic the pathological state of IVDD in vitro: GRh2 restored NP cell viability, alleviated extracellular matrix damage, repaired autophagic function, and inhibited pyroptosis. Through network pharmacology and molecular docking, HIF-1α was identified as a key functional pathway; blocking HIF-1α with BAY872243 completely abolished the aforementioned effects of GRh2. In rat IVDD models, GRh2 maintained disc structural stability and extracellular matrix homeostasis, while BAY872243 reversed this protective effect. In conclusion, GRh2 alleviates IVDD by activating autophagy mediated by HIF-1α, as well as inhibiting pyroptosis and extracellular matrix damage, making it a potential therapeutic agent for IVDD.