Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolia, China.
The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010010, Inner Mongolia, China.
J Orthop Surg Res. 2023 Jul 31;18(1):552. 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.
那如-3 丸是一种治疗椎间盘退行性变（IDD）的蒙药，但作用机制尚不清楚。
本研究旨在探讨那如-3 丸治疗 IDD 的作用机制。
从公共数据库中收集那如-3 丸的活性成分及相关靶点和 IDD 相关基因，采用蛋白质-蛋白质相互作用网络分析、基因本体论和京都基因与基因组百科全书（KEGG）功能富集分析、分子对接和分子动力学模拟等方法进行分析，最后通过体外实验对网络药理学结果进行验证。
网络分析显示，芝麻素、胡椒碱和鞣花酸可能是潜在的关键成分，CASP3、BAX 和 BCL2 是关键靶点。KEGG 分析表明，细胞凋亡途径可能是潜在的作用途径。分子对接显示，芝麻素与靶点的相互作用优于其他成分。分子动力学模拟结果表明，BAX-芝麻素、BCL2-芝麻素和 CASP3-芝麻素 3 个系统在模拟过程中均稳定合理。体外实验表明，芝麻素对细胞生长的影响最小，促增殖作用最显著，因此被认为是关键成分。实验证实芝麻素有抗凋亡作用，并逆转退变模型中 CASP3、BAX 和 BCL2 的表达，与网络药理学结果一致。此外，芝麻素可减轻 IDD 模型中细胞外基质（ECM）退变，促进细胞增殖。
本研究表明，那如-3 丸可能通过延缓 ECM 降解和促进细胞增殖来发挥其治疗和抗凋亡作用，为治疗 IDD 提供了新策略。
