A review of Duhuo Jisheng decoction mechanisms in intervertebral disc degeneration in vitro and animal studies

Abstract

Intervertebral disc degeneration (IVDD) has become a serious public health problem, placing a heavy burden on society and the healthcare system. Its pathogenesis is not completely clear and may be closely related to mechanical damage, inflammatory factors, oxidative stress and death of nucleus pulposus cells (NPCs). The treatment of IVDD mainly includes conservative treatment and surgery. Conservative treatment is based on hormonal and anti-inflammatory drugs and massage techniques, which can relieve the pain symptoms to a certain extent, but cannot solve the problem from the root cause. Surgical treatment is mainly by removing the herniated nucleus pulposus, but it is more traumatic for IVDD patients, expensive and not suitable for all patients. Therefore, it is extremely important to clarify the pathogenesis of IVDD, to find an effective and convenient treatment and to further elaborate its mechanism of action. The effectiveness of traditional Chinese medicine in the treatment of IVDD has been well demonstrated in clinical medical research. We have been working on the Chinese herbal formula Duhuo Jisheng Decoction, which is a common formula for the treatment of degenerative disc disease. Not only does it have significant clinical effects, but it also has few adverse effects. At present, we found that its mechanism of action mainly involves regulation of inflammatory factors, reduction of apoptosis and pyroptosis of NPCs, inhibition of extracellular matrix degradation, improvement of intestinal flora, etc. However, a few relevant articles have yet comprehensively and systematically summarized the mechanisms by which they exert their effect. Therefore, this paper will comprehensively and systematically explain on it. This is of great clinical significance and social value for elucidating the pathogenesis of IVDD and improving the symptoms of patients, and will provide a theoretical basis and scientific basis for the treatment of IVDD with traditional Chinese medicine.

Keywords: Duhuo Jisheng decoction; Intervertebral disc degeneration; Molecular mechanism; Traditional Chinese medicine.

Fig. 1

Schematic diagram of the structure of normal and degenerated discs. A The normal intervertebral disc is composed of the fibrous annulus (AF), cartilage end plate (CEP) and nucleus pulposus (NP), all three of which provide the basis for disc homeostasis. B In degenerated discs, the nucleus pulposus (NP) tissue protrudes outward to compress nerve roots and blood vessels, and inflammatory factors are released and accumulate, exacerbating the degree of disc degeneration

Fig. 2

Schematic diagram of the NF-κB signaling pathway and its associated mechanisms. Factors such as IL-1β and TNF-α are used as promoters that mediate signal expression, leading to the expression of inflammatory proteins such as IL-18, IL-1β, COX-2, MMP and other inflammatory factors. and mediates the degradation of extracellular matrix and the death of NPCs

Fig. 3

Schematic diagram of MAPK signaling pathway and its related mechanisms. Factors such as IL-1 and TNF are used as promoters that mediate signal expression, and JNK, p38 and ERK are three isoforms of the MAPK pathway. Ultimately, it mediates apoptosis of NPCs. This pathway exists in crosstalk with the NF-κB pathway and shares a common promoter

Fig. 4

Schematic diagram of the cascade response to disc degeneration. In degenerated discs, NPCs are stimulated by various degenerative factors that induce the release of inflammatory mediators (IL, INF-γ, TNF-α, etc.), and inflammatory cytokines activate sensory neurons and produce pain. IL-1β and TNF-α act as promoters to activate NF-κB and MAPK pathways and are involved in the production of cytokines, chemokines and extracellular matrix degradation factors in IVD. leading to inflammation and extracellular matrix degradation as well as death of NPCs

Fig. 5

Diagram of the relationship between intestinal flora dysbiosis and intervertebral disc degeneration. The Bacteroidetes acts on the NF-κB signaling pathway to produce an inflammatory response, and Clostridium perfringens in the Firmicutes, which slows disc degeneration by modulating immunity with the release of anti-inflammatory factors

Fig. 6

A Changes in abundance of different intestinal flora based on gate-level IVDD and DHJSD treatment. B Proportion of serum metabolites classified in IVDD based on serum metabolite analysis. C Heat map of association analysis between intestinal flora and serum metabolites in normal group and IVDD model group. D Heat map of association analysis between intestinal flora and serum metabolites in IVDD model group and DHJSD treatment group (red indicates positive correlation, blue indicates negative correlation *P < 0.05)