Mechanism of notoginsenoside R1 in alleviating intervertebral disc degeneration: an experimental and network...

Notoginsenoside R1 (NGR1) shows therapeutic potential in intervertebral disc degeneration (IDD), but its mechanism remains unclear.An in vivo rat tail puncture model and in vitro erastin-induced nucleus pulposus (NP) cells were employed to evaluate the therapeutic effects and underlying mechanisms of NGR1 on IDD. Network pharmacology was performed to predict potential NGR1 targets, which were validated using qRT-PCR. 3-MA (an autophagy inhibitor) and colivelin (a STAT3 activator) were used for mechanistic validation.NGR1 improved disc structure and significantly increased aggrecan and collagen II levels in NP tissues. NGR1 inhibited ferroptosis, as evidenced by increased GPX4 and decreased ACSL4, Fe²⁺, and ROS levels. NGR1 also promoted autophagy, as indicated by increased Beclin-1 and LC3 II/I levels in NP tissues. Moreover, serum IL-1β and IL-6 were reduced by NGR1 in IDD rats. NGR1 significantly reduced the levels of predicted targets STAT3, IL1B, and MAPK3. In erastin-induced NP cells, NGR1 significantly restored cell viability, enhanced autophagy, and suppressed ferroptosis as well as STAT3, IL1B, and MAPK3 expression, all of which were partially reversed by 3-MA or colivelin.NGR1 alleviates IDD by inhibiting ferroptosis and promoting autophagy, potentially via STAT3 signalling, thereby preserving disc integrity and delaying disease progression.