Department of Pediatrics, Maternal and Child Health Hospital of Yancheng, No. 21 Century avenue, Yancheng, 224002, Jiangsu Province, China.
Pediatric neurology department, Children's Hospital Affiliated To Suzhou University, No. 50 Donghuan road, Suzhou, 215000, Jiangsu Province, China.
BMC Complement Med Ther. 2021 Jan 6;21(1):9. doi: 10.1186/s12906-020-03178-x.
BACKGROUND: Epilepsy, one of the most common neurological disorders, affects over 70 million people worldwide. Rhynchophylline displays a wide variety of pharmacologic actives. However, the pharmacologic effects of rhynchophylline and its mechanisms against epilepsy have not been systematically elucidated.
The oral bioavailability and druglikeness of rhynchophylline were evaluated using the Traditional Chinese Medicine Systems Pharmacology Database. Rhynchophylline target genes to treat epilepsy were identified using PharmMapper, SwissTargetPrediction and DrugBank databases integration. Protein-protein interaction analysis was carried out by utilizing the GeneMANIA database. WebGestalt was employed to perform Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The drug-disease-target-Gene Ontology-pathway network was constructed using Cytoscape.
The oral bioavailability and druglikeness of rhynchophylline were calculated to be 41.82% and 0.57, respectively. A total of 20 rhynchophylline target genes related to epilepsy were chosen. Among the 20 genes and their interacting genes, 54.00% shared protein domains and 16.61% displayed co-expression characteristics. Gene ontology, Kyoto Encyclopedia of Genes and Genomes and network analyses illustrate that these targets were significantly enriched in regulation of sensory perception, morphine addiction, neuroactive ligand-receptor interaction and other pathways or biological processes.
In short, rhynchophylline targets multiple genes or proteins, biological processes and pathways. It shapes a multiple-layer network that exerts systematic pharmacologic activities on epilepsy.
背景：癫痫是最常见的神经系统疾病之一，影响着全球超过 7000 万人。钩藤碱具有广泛的药理活性。然而，钩藤碱的药理作用及其治疗癫痫的机制尚未得到系统阐明。方法：利用中药系统药理学数据库评估了钩藤碱的口服生物利用度和类药性。利用 PharmMapper、SwissTargetPrediction 和 DrugBank 数据库整合，确定治疗癫痫的钩藤碱靶基因。利用 GeneMANIA 数据库进行蛋白质-蛋白质相互作用分析。利用 WebGestalt 进行基因本体论和京都基因与基因组百科全书通路富集分析。使用 Cytoscape 构建药物-疾病-靶标-基因本体论-通路网络。结果：计算得出钩藤碱的口服生物利用度和类药性分别为 41.82%和 0.57。选择了 20 个与癫痫相关的钩藤碱靶基因。在这 20 个基因及其相互作用基因中，有 54.00%共享蛋白质结构域，16.61%显示出共表达特征。基因本体论、京都基因与基因组百科全书和网络分析表明，这些靶标显著富集在感觉知觉调节、吗啡成瘾、神经活性配体-受体相互作用等通路或生物学过程中。结论：总之，钩藤碱靶向多个基因或蛋白质、生物学过程和通路。它形成了一个多层次的网络，对癫痫产生系统的药理作用。
