Pharmacological Mechanism of Danggui-Sini Formula for Intervertebral Disc Degeneration: A Network Pharmacology Study

Wang L, Lin J, Li W · BioMed Research International · 2021 November 11

DOI 10.1155/2021/5165075

Objective

To investigate the molecular biological mechanism of Danggui-Sini formula (DSF) in treating intervertebral disc degeneration (IVDD) using network pharmacology and molecular docking.

Conclusions

The study identified 119 active ingredients and 136 common genes, with 10 core genes (AKT1, IL6, ALB, TNF, VEGFA, TP53, MAPK3, CASP3, JUN, and EGF). Enrichment analysis revealed involvement in pathways such as the AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, apoptosis, cellular senescence, PI3K-Akt signaling pathway, and FoxO signaling pathway. Molecular docking confirmed stable affinity between core genes and key components, supporting the "multicomponent, multitarget, and multipathway" characteristics of DSF in IVDD treatment.

Critical Appraisal

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Insights

Dang Gui Si Ni formula moderates intervertebral disc degeneration by primarily interacting with stress responses and apoptotic signaling pathways.

The study used traditional Chinese medicine SP (TCMSP), UniProt, and five disease gene databases to identify a gene set possibly responsive to DSF treatment of IVDD. In order to establish a protein interaction network involving DSF and IVDD, the STRING database was used. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R platform, in order to deduce potential mechanisms. Molecular docking including the calculation of binding energy, was validated with AutoDock Vina. Subsequent to the identification of 119 active ingredients and 136 shared genes, the study reveals 10 core genes that are involved. Enrichment analysis signposts that DSF's therapeutic targets are primary focusses on certain signaling pathways relating to diabetic complications, Interleukin (IL)-17, Tumor Necrosis Factor (TNF), Toll-like receptor, apoptosis, cellular senescence, PI3K-Akt, and FoxO. Reactive oxygen species and stress responses as well as the controlling of apoptotic signalling pathways are the main biological processes these focus on. A stable affinity between the key components and the core genes was shown by molecular docking. Overall, the study used a combination of network pharmacology and molecular docking to affirm the multi-target and multi-pathway attributes of DSF for IVDD treatment.