Li Shaoshuo, Shao Yang, Chen Hao, Wang Jianwei
Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Traumatology and Orthopedics, Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine, Wuxi 214071, China.
Evid Based Complement Alternat Med. 2022 Feb 27;2022:4932153. doi: 10.1155/2022/4932153. eCollection 2022.
To identify the potential pharmacological targets of Jisuikang (JSK) for the treatment of spinal cord injury (SCI) using network pharmacology.
The bioactive compounds of JSK herbs and their corresponding potential SCI targets were obtained from three traditional Chinese medicine (TCM) databases. SCI-related therapeutic target genes were obtained from the Comparative Toxicogenomics Database and the GeneCards Database. The common target genes between the JSK compounds and SCI-related therapeutic targets were screened using GO/KEGG functional enrichment and protein-protein interaction (PPI) analyses to identify hub genes and their categories of biological function. Gene expression distribution and receiver operating characteristic curve (ROC) analyses were used to identify probable SCI-related target genes. Molecular docking was used to quantify molecular interactions between target genes and the bioactive compounds of JSK.
A total of 183 JSK bioactive compounds and 197 target genes for the treatment of SCI were screened and assessed. The target genes were enriched primarily in drug metabolism and in inflammation-related biological processes. Ten genes with statistical significance were identified as therapeutic SCI-related target genes of JSK. Molecular docking experiments demonstrated that the proteins of these 10 genes docked with binding energies of less than -5 kcal/mol with the bioactive compounds in JSK.
This study showed that the anti-SCI effects of JSK may be mediated through numerous bioactive components, multiple gene targets, and inflammation-related pathways and provided potential novel targets for directed therapies for treating SCI. These results provide a foundation for further experimental investigations into treatment options for SCI.
运用网络药理学方法确定芪髓康(JSK)治疗脊髓损伤(SCI)的潜在药理靶点。
从三个中药数据库获取JSK药材的生物活性成分及其相应的潜在SCI靶点。从比较毒理基因组学数据库和基因卡片数据库获取SCI相关治疗靶点基因。利用GO/KEGG功能富集和蛋白质-蛋白质相互作用(PPI)分析筛选JSK化合物与SCI相关治疗靶点之间的共同靶点基因,以确定枢纽基因及其生物学功能类别。采用基因表达分布和受试者工作特征曲线(ROC)分析来确定可能与SCI相关的靶点基因。运用分子对接来量化靶点基因与JSK生物活性化合物之间的分子相互作用。
共筛选并评估了183种JSK生物活性化合物和197个治疗SCI的靶点基因。这些靶点基因主要富集于药物代谢和炎症相关的生物学过程。确定了10个具有统计学意义的基因作为JSK治疗SCI的相关靶点基因。分子对接实验表明,这10个基因的蛋白质与JSK中的生物活性化合物对接时结合能小于-5 kcal/mol。
本研究表明,JSK的抗SCI作用可能通过多种生物活性成分、多个基因靶点和炎症相关途径介导,为SCI的定向治疗提供了潜在的新靶点。这些结果为进一步开展SCI治疗方案的实验研究奠定了基础。