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

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

  • J Orthop Surg Res. 2023 Jul 31;18(1):552. doi: 10.1186/s13018-023-04014-x.
Jialin Guo # 1,  Jianmin Xue # 2,  Zhiwei He 1,  Haiyu Jia 3,  Xuejun Yang 4
Affiliations

Affiliations

  • 1 Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolia, China.
  • 2 The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010010, Inner Mongolia, China.
  • 3 The Affiliated Hospital of Inner Mongolia Medical University, NO.1 North Tongdao Road, Hohhot, 010030, Inner Mongolia, China. [email protected].
  • 4 Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, NO.42 Zhaowuda Road, Hohhot, 010010, Inner Mongolia, China. [email protected].
  • # Contributed equally.
PMID: 37525208 DOI: 10.1186/s13018-023-04014-x
Abstract

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.

Keywords

Apoptosis; Intervertebral disc degeneration; Naru 3 pill; Pharmacological mechanisms; Sesamin.

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