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Natural products targeting programmed cell death: a novel therapeutic strategy for intervertebral disc degeneration
Shudong Li1, Tao Yang2,3, Rongchen Lu1
1The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Abstract:
Intervertebral disc degeneration (IVDD) serves as a central pathological mechanism in the development of spinal degenerative disorders. Its progression is closely associated with the dysregulated activation of various programmed cell death (PCD) pathways, including apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy. Recent investigations have highlighted the potential of natural products to modulate these cell death processes through multitarget mechanisms, making them promising candidates for IVDD intervention. In this study, a comprehensive literature search was conducted using the PubMed database (up to 2025), applying a dual search strategy to systematically identify relevant publications. Following the screening of titles and abstracts and the removal of nonoriginal publications, a total of 194 eligible studies were retained, covering 134 distinct natural products. The analysis revealed that these products are capable of targeting multiple PCD pathways in intervertebral disc cells and exhibit considerable therapeutic potential. These findings offer a theoretical framework and methodological reference for the development of novel treatments for IVDD. Nevertheless, limitations remain regarding natural products, particularly in terms of bioavailability and safety. Future efforts should focus on optimizing screening platforms and drug delivery strategies to enhance therapeutic efficacy while minimizing potential toxicity.
Insights
Natural products show promise for treating intervertebral disc degeneration (IVDD) by targeting multiple programmed cell death (PCD) pathways. Further research is needed to improve their bioavailability and safety for effective IVDD therapies.
Area of Science:
- Biomedical Science
- Pharmacology
- Regenerative Medicine
Background:
- Intervertebral disc degeneration (IVDD) is a primary cause of spinal disorders.
- IVDD progression involves dysregulated programmed cell death (PCD) pathways like apoptosis, pyroptosis, necroptosis, ferroptosis, and autophagy.
- Natural products offer multitarget mechanisms to modulate PCD pathways, presenting therapeutic potential for IVDD.
Purpose of the Study:
- To systematically review natural products targeting PCD pathways in IVDD.
- To assess the therapeutic potential of natural products for IVDD intervention.
- To provide a framework for developing novel IVDD treatments.
Main Methods:
- Comprehensive literature search of the PubMed database up to 2025.
- Dual search strategy for systematic identification of relevant publications.
- Screening of titles and abstracts, excluding non-original research, to select eligible studies.
Main Results:
- 194 eligible studies were included, detailing 134 distinct natural products.
- Natural products were found to target multiple PCD pathways in intervertebral disc cells.
- Significant therapeutic potential for IVDD was identified across various natural products.
Conclusions:
- Natural products demonstrate considerable potential for IVDD treatment by modulating diverse PCD pathways.
- Limitations include challenges with natural product bioavailability and safety.
- Future research should focus on optimizing screening and drug delivery for enhanced efficacy and reduced toxicity.
