Traditional Chinese Medicine compound formula and effective ingredients for treating intervertebral disc degeneration: a multi-targeted and holistic regulation concept

Abstract

BACKGROUND: Traditional Chinese Medicine (TCM) has significant potential and benefits in the treatment of intervertebral disc degeneration. However, reviews on the mechanisms by which TCM ameliorates disc degeneration are relatively limited. OBJECTIVE: To review how TCM compounds and their active ingredients improve intervertebral disc degeneration through mechanisms such as anti-inflammation, antioxidative stress, maintenance of extracellular matrix balance and regulation of programmed cell death. METHODS: CNKI, WanFang, PubMed, and Web of Science were retrieved for relevant literature published from January 2001 to June 2025. The Chinese search terms were “Chinese herb, compound, traditional Chinese medicine, herbal medicine, soup, formula, degenerative disc disease, disc degeneration, disc injury, annulus fibrosus, cartilage endplates, nucleus pulposus, research, progress, review, experiment, inflammation, oxidative stress, extracellular matrix, programmed cell death, apoptosis, pyroptosis, ferroptosis, autophagy, immune cells, mechanism”, and English search terms were “Traditional Chinese medicine, herbal medicine, herbal formula, Intervertebral Disc Degeneration, Intervertebral Disc, disc degeneration, nucleus pulposus, annulus fibrosus, cartilage endplate, Oxidative Stress, Extracellular Matrix, Inflammation, Programmed Cell Death, Apoptosis, Pyroptosis, Ferroptosis, Autophagy, review, progress, experiment”. According to inclusion and exclusion criteria, 104 articles were finally included for review. RESULTS AND CONCLUSION: TCM can effectively inhibit the release of inflammatory factors and activation of inflammatory pathways through multiple mechanisms, improving the local inflammatory state of the intervertebral disc, but the specific mechanisms in immune cell-mediated inflammatory responses remain unclear. TCM shows strong multi-target regulatory ability in alleviating oxidative stress in the intervertebral disc, especially in enhancing antioxidant enzyme activity, stabilizing mitochondrial function, and inhibiting reactive oxygen species accumulation. However, systematic comparisons of antioxidant effects of different active ingredients in different disc cell types are lacking, and the crosstalk between related signaling pathways needs further exploration. TCM can effectively alleviate disc structural disruption by regulating extracellular matrix synthesis and degradative enzyme activity. Apoptosis, pyroptosis, ferroptosis, and autophagy collectively participate in the development of intervertebral disc degeneration; they are not isolated but interact through complex signaling networks. Therefore, the multi-target and holistic regulatory advantages of TCM are expected to simultaneously regulate multiple programmed cell death processes, protecting disc cells from multiple levels and delaying degeneration.

1. Introduction

Intervertebral disc degeneration is a degenerative process characterized by structural disruption and dysfunction of the intervertebral disc under the influence of various internal and external factors such as mechanical stress, aging, and inflammation. It involves multiple tissue structures including the nucleus pulposus, annulus fibrosus, and cartilage endplates, and is progressive and multifactorial in nature [1-2]. Disc degeneration can affect cervical, thoracic, and lumbar segments, serving as the primary anatomical basis for common spinal disorders such as neck pain, thoracic back pain, and low back pain. Epidemiological data indicate that low back pain is a major cause of productivity loss worldwide and the leading cause of disability in 126 countries, with disc degeneration considered the main pathological basis. Therefore, low back pain caused by disc degeneration is a global public health issue, severely impacting patients' quality of life and imposing a substantial economic burden on individuals and society [3].

Currently, although surgical treatment can relatively effectively alleviate patient suffering, it does not target the underlying pathogenesis and carries perioperative risks. For patients with early-stage disc degeneration or contraindications to surgery, effective non-surgical treatments are lacking. Hence, exploring new anti-degenerative drugs holds great economic and social significance. In recent years, novel approaches such as gene and molecular therapies have been applied to improve disc degeneration, but they still face numerous challenges. Traditional Chinese Medicine (TCM) offers unique advantages in the prevention and treatment of degenerative diseases, including abundant targets, fewer adverse effects, and definite efficacy [4], showing great potential in treating disc degeneration. Despite the diverse mechanisms reported for TCM in improving disc degeneration [5], systematic reviews of these therapeutic mechanisms remain insufficient. This review systematically summarizes research progress on TCM compounds and their active ingredients in intervening in disc degeneration, categorizing them into four core mechanisms: anti-inflammation, antioxidative stress, maintenance of extracellular matrix balance, and regulation of programmed cell death (Figure 1), providing new insights and directions for TCM treatment of disc degeneration.