Ginsenoside Rh2 Attenuates Intervertebral Disc Degeneration by Modulating the PI3K/AKT Signaling Pathway to Suppress Apoptosis

Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain and imposes a substantial socioeconomic burden. Ginsenoside Rh2 (Gin-Rh2), a bioactive ginseng compound with antioxidant properties, may have therapeutic potential in IVDD, but its effects and underlying mechanisms remain unclear. Here, we evaluated Gin-Rh2 in cellular and rat models of IVDD. In vitro, Gin-Rh2 attenuated interleukin-1β (IL-1β)-induced nucleus pulposus cell apoptosis, reduced matrix metalloproteinase-3 (MMP3) expression, and increased aggrecan and type II collagen production. Network pharmacology and molecular docking implicated the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway as a potential target. Mechanistic experiments further indicated that inhibition of PI3K/AKT signaling contributed to the protective effects of Gin-Rh2, whereas pharmacological activation of this pathway partially attenuated these effects. In vivo, Gin-Rh2 attenuated puncture-induced disc degeneration. Collectively, these findings suggest that Gin-Rh2 protects nucleus pulposus cells and attenuates experimental IVDD, supporting its further investigation as a potential therapeutic candidate.