The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification
Authors
Jialin Guo
Inner Mongolia Medical University, Hohhot, 010050 Inner Mongolia China
Jianmin Xue
The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010010 Inner Mongolia China
Zhiwei He
Inner Mongolia Medical University, Hohhot, 010050 Inner Mongolia China
Haiyu Jia
The Affiliated Hospital of Inner Mongolia Medical University, NO.1 North Tongdao Road, Hohhot, 010030 Inner Mongolia China
Xuejun Yang
Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, NO.42 Zhaowuda Road, Hohhot, 010010 Inner Mongolia China
Context
Naru 3 pill is a traditional Mongolian medicine for the treatment of intervertebral disc degeneration (IDD), but the mechanism is not yet clear.
Objective
This study investigated the mechanism of Naru 3 pill in the treatment of IDD.
Materials and methods
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.
Results
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.
Conclusion
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.
Supplementary Information
The online version contains supplementary material available at 10.1186/s13018-023-04014-x.
Keywords: Intervertebral disc degeneration, Naru 3 pill, Sesamin, Pharmacological mechanisms, Apoptosis
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