Harnessing natural products to target programmed cell death for intervertebral disc degeneration: Mechanisms and opportunity

Songlin Liang; Zhichao Li; Renchang Chen; Shang Gao; Xintian Qu; Chenmoji Wang; Di Gao; Hao Wang; Jiatong Li; Nianhu Li

doi:10.1016/j.jpha.2026.101583

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Songlin Liang, Zhichao Li, Renchang Chen, Shang Gao, Xintian Qu, Chenmoji Wang, Di Gao, Hao Wang, Jiatong Li, Nianhu Li. Harnessing natural products to target programmed cell death for intervertebral disc degeneration: Mechanisms and opportunity[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101583

Citation:

Songlin Liang, Zhichao Li, Renchang Chen, Shang Gao, Xintian Qu, Chenmoji Wang, Di Gao, Hao Wang, Jiatong Li, Nianhu Li. Harnessing natural products to target programmed cell death for intervertebral disc degeneration: Mechanisms and opportunity[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101583

Citation:

Songlin Liang, Zhichao Li, Renchang Chen, Shang Gao, Xintian Qu, Chenmoji Wang, Di Gao, Hao Wang, Jiatong Li, Nianhu Li. Harnessing natural products to target programmed cell death for intervertebral disc degeneration: Mechanisms and opportunity[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101583

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Harnessing natural products to target programmed cell death for intervertebral disc degeneration: Mechanisms and opportunity

doi: 10.1016/j.jpha.2026.101583

First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China

Funds:

This work was supported by the National Expert Inheritance Studio in Traditional Chinese Medicine, China (Grant No.: GZY-KJS-2022-75), the Natural Science Foundation of Shandong Province, China (Grant No.: ZR2023MH063), the Jinan Clinical Medicine Innovation Program, China (Grant No.: 202328081), the Joint Research Program of the National Administration of Traditional Chinese Medicine, China (Grant No.: GZY-KJS-SD-2023-042), and 2024 Doctoral Research Quality Improvement and Innovation Plan of Shandong University of Traditional Chinese Medicine, China (Grant No.: YJSTZCX2024038).

Received Date: Jun. 08, 2025
Accepted Date: Feb. 07, 2026
Rev Recd Date: Feb. 04, 2026
Available Online: Feb. 10, 2026

Abstract

Abstract

Intervertebral disc (IVD) degeneration (IVDD) is a common age-related degenerative disorder and a leading cause of disability and mobility impairment in adults. It is characterized by dysfunction of nucleus pulposus cells (NPCs), annulus fibrosus (AF) cells (AFCs), and cartilage endplate (CEP) cells (CEPCs), triggered by aging, inflammation, and nutrient deprivation. These cellular alterations ultimately result in structural deterioration and functional impairment of the IVD. Programmed cell death (PCD), a key regulatory mechanism governing cell fate, precisely controls survival or elimination through highly conserved and specifically activated signaling cascades. Growing evidence indicates that natural products can modulate PCD pathways and slow IVDD progression, highlighting their potential as complementary therapies or novel drug candidates for IVDD management. In light of recent advances, this review systematically summarizes the mechanisms and interactive networks of six major PCD types: apoptosis, autophagy, ferroptosis, pyroptosis, necroptosis, and PANoptosis. It further explores how natural products regulate these processes to mitigate IVDD, as well as their prospects and strategies for clinical translation. Together, these insights provide a foundation for developing natural product-based therapeutics against IVDD.
- Natural products,
- Programmed cell death,
- Intervertebral disc degeneration,
- Phytoconstituents

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References(150)

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