Molecular Mechanism of Duhuo Jisheng Decoction in Delaying Intervertebral Disc Degeneration Based on Network Pharmacology and Experimental Validation
LI Junwen
LIU Shufen
LI Shipian
LIN Haowen
ZHANG Mengjie
YAN Ming
YAO Min
CUI Xuejun
Abstract：Objective To investigate the mechanism of Duhuo Jisheng decoction in delaying intervertebral disc degeneration(IDD).Methods The chemical components of Duhuo Jisheng decoction were identified using high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS).Network pharmacology was employed to analyze the potential mechanisms of Duhuo Jisheng decoction in intervening in IDD.A tail intervertebral disc puncture model was used to observe pathological changes in intervertebral disc tissues through HE staining and safranin O-fast green staining.Western blot and immunofluorescence were performed to detect the expression of type II collagen(COL2A),interleukin(IL)-6,IL-17,IL-1β,Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),nuclear factor-κB(NF-κB),phosphorylated NF-κB(p-NF-κB),NOD-like receptor thermal protein domain-associated protein 3(NLRP3),cleaved caspase-1,and apoptosis-associated speck-like protein(ASC).Results Mass spectrometry analysis of the compound primarily identified components such as kaempferol,formononetin,5-methoxyvisamminol,glabridin,and calycosin.The intersection of detected components and network targets yielded 37 common targets.KEGG and GO enrichment analyses indicated that key pathways mainly involved TNF and IL-17 signaling pathways,as well as TLR4/MyD88/NF-κB and NLRP3 inflammasome-related pathways.These pathways were also associated with processes such as oxidative stress response,vesicle structure,and protein homodimerization activity.It was thus hypothesized that the therapeutic mechanism may be related to inflammatory responses,among others.Animal experiments confirmed that compared with the control group,IDD model rats exhibited significant reductions in intervertebral disc height,decreased nucleus pulposus tissue content,and disorganization of the annulus fibrosus.Administration of Duhuo Jisheng decoction significantly alleviated these phenomena.Duhuo Jisheng decoction increased the downregulated expression of COL2A protein in the model group and reversed the upregulated expression of IL-6,IL-17,IL-1β,p-NF-κB,TLR4,MyD88,NLRP3,cleaved caspase-1,and ASC proteins.Conclusion Duhuo Jisheng decoction delays the progression of IDD by regulating inflammatory signaling pathways such as TNF and IL-17.
Keywords：Duhuo Jisheng decoctionIntervertebral disc degenerationIL-17 signaling pathwayNetwork pharmacology
Publication Date：2026-03-28
Online Publishing Date：2026-03-31(First online date of this platform, not the publication date of the document)
Pages：8( 589-596 )