Natural Products for Intervertebral Disc Degeneration: Mechanistic Insights and Therapeutic Potentials

Zenghan Wu¹Jiang Chen²Wenhai Luo¹Tao Kuang^1*

• ¹The First Hospital of Hunan University of Chinese Medicine, Changsha, China
• ²Ningbo Chinese Medicine Hospital, Ningbo, Zhejiang Province, China

Intervertebral disc degeneration (IDD) is a leading cause of spinal disorders worldwide. Current clinical therapies for IDD are often constrained by limited efficacy, notable adverse effects, and high treatment costs. Thus, there is a pressing need for safer and more effective treatment strategies. In recent years, natural product-based therapies have garnered increasing attention due to their multi-target mechanisms and relatively low toxicity. This review comprehensively summarizes recent advances in the application of natural products for IDD treatment, with a focus on flavonoids (e.g., quercetin, hyperoside), glycosides (e.g., ginsenosides, notoginsenosides), terpenoids (e.g., aucubin, celastrol), phenolic compounds (e.g., curcumin, resveratrol), and alkaloids (e.g., berberine, evodiamine). These compounds exert their therapeutic effects by modulating critical signaling pathways, including Sirtuin-1 (SIRT1), Nuclear Factor-kappa B (NF-κB), Mitogen-Activated Protein Kinase (MAPK), Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/Akt), and Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2). Collectively, they exhibit potent anti-inflammatory, antioxidant, anti-apoptotic, anti-senescence, and regenerative properties. The insights presented herein provide a robust theoretical foundation to support future preclinical and clinical investigations, highlighting the considerable promise of natural products in IDD management.Schematic illustration of the major signaling pathways modulated by natural products in the treatment of IDD. Representative compound categories-including flavonoids, glycosides, terpenoids, phenolic compounds, and alkaloids-target key molecular pathways such as NF-κB, SIRT1/Nrf2, PI3K/Akt, MAPK (p38/JNK/ERK), and AMPK/mTOR. These pathways are involved in reducing inflammation and apoptosis, enhancing ECM stability and cell viability, and promoting autophagy, collectively contributing to the attenuation of IDD progression.