The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification

• Published in: Journal of orthopaedic surgery and research Vol. 18; no. 1; pp. 552 - 18
• Main Authors: Guo, Jialin, Xue, Jianmin, He, Zhiwei, Jia, Haiyu, Yang, Xuejun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.07.2023; BioMed Central; BMC
• Subjects: Analysis; Apoptosis; BAX protein; Bcl-2 protein; bcl-2-Associated X Protein; Bioinformatics; Cartilage; Caspase 3; Cell proliferation; Computer simulation; Degeneration; Degenerative disc disease; Ellagic acid; Extracellular matrix; Gene set enrichment analysis; Genes; Genomes; Genomics; Humans; Interdisciplinary subjects; Intervertebral Disc; Intervertebral disc degeneration; Intervertebral Disc Degeneration - drug therapy; Intervertebral discs; Ligands; Molecular Docking Simulation; Molecular dynamics; Naru 3 pill; Network Pharmacology; Ontology; Orthopedics; Pharmacological mechanisms; Pharmacology; Physiological aspects; Piperine; Polymerase chain reaction; Protein-protein interactions; Proteins; Sesamin; Software; Traditional Chinese medicine; Mongolia; Japan; China; United States > US; Intervertebral disc degeneration; Sesamin; Naru 3 pill; Pharmacological mechanisms; Apoptosis
• ISSN: 1749-799X; 1749-799X
• DOI: 10.1186/s13018-023-04014-x

Naru 3 pill is a traditional Mongolian medicine for the treatment of intervertebral disc degeneration (IDD), but the mechanism is not yet clear. This study investigated the mechanism of Naru 3 pill in the treatment of IDD. Active ingredients and related targets of Naru 3 pill, as well as IDD-related genes, were collected from public databases. The analysis was performed by protein‒protein interaction network analysis, gene ontology and Kyoto Gene and Genome Encyclopedia (KEGG) functional enrichment analysis, molecular docking and molecular dynamics simulations. Finally, the network pharmacology results were validated by in vitro experiments. Network analysis showed that sesamin, piperine and ellagic acid were potential key components and CASP3, BAX and BCL2 were key targets. KEGG analysis indicated the apoptotic pathway as a potential pathway. Molecular docking showed that sesamin interacted better with the targets than the other components. The results of molecular dynamics simulations indicated that the three systems BAX-sesamin, BCL2-sesamin and CASP3-sesamin were stable and reasonable during the simulation. In vitro experiments showed that sesamin had the least effect on cell growth and the most pronounced proliferation-promoting effect, and so sesamin was considered the key component. The experiments confirmed that sesamin had antiapoptotic effects and reversed the expression of CASP3, BAX and BCL2 in degeneration models, which was consistent with the network pharmacology results. Furthermore, sesamin alleviated extracellular matrix (ECM) degeneration and promoted cell proliferation in the IDD model. The present study suggested that Naru 3 pill might exert its therapeutic and antiapoptotic effects on IDD by delaying ECM degradation and promoting cell proliferation, which provides a new strategy for the treatment of IDD.