The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification
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 relat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-023-04014-x |
| _version_ | 1827875498195156992 |
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| author | Jialin Guo Jianmin Xue Zhiwei He Haiyu Jia Xuejun Yang |
| author_facet | Jialin Guo Jianmin Xue Zhiwei He Haiyu Jia Xuejun Yang |
| author_sort | Jialin Guo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T17:07:47Z |
| format | Article |
| id | doaj.art-fda8f76fcfef471e8cd83d2be8aaa56c |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-03-12T17:07:47Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-fda8f76fcfef471e8cd83d2be8aaa56c2023-08-06T11:20:25ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2023-07-0118111810.1186/s13018-023-04014-xThe mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verificationJialin Guo0Jianmin Xue1Zhiwei He2Haiyu Jia3Xuejun Yang4Inner Mongolia Medical UniversityThe Second Affiliated Hospital of Inner Mongolia Medical UniversityInner Mongolia Medical UniversityThe Affiliated Hospital of Inner Mongolia Medical UniversityPeking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical UniversityAbstract 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.https://doi.org/10.1186/s13018-023-04014-xIntervertebral disc degenerationNaru 3 pillSesaminPharmacological mechanismsApoptosis |
| spellingShingle | Jialin Guo Jianmin Xue Zhiwei He Haiyu Jia Xuejun Yang The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification Journal of Orthopaedic Surgery and Research Intervertebral disc degeneration Naru 3 pill Sesamin Pharmacological mechanisms Apoptosis |
| title | The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification |
| title_full | The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification |
| title_fullStr | The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification |
| title_full_unstemmed | The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification |
| title_short | The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification |
| title_sort | mechanism by which naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification |
| topic | Intervertebral disc degeneration Naru 3 pill Sesamin Pharmacological mechanisms Apoptosis |
| url | https://doi.org/10.1186/s13018-023-04014-x |
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