枸杞子治疗视网膜色素变性分子机制的网络药理学研究
A Network Pharmacology Approach to Uncover the Molecular Targets and Associated Potential Pathways of Lycii Fructus for the Treatment of Retinitis Pigmentosa
摘要
Abstract
Objective To explore the molecular targets and associated potential pathways of Lycii Fructus (LF, Gou Qi Zi, 枸杞子) in the treatment of retinitis pigmentosa (RP) by the approaches of network pharmacology and bioinformatics. Methods The potential blood-entry active ingredients and targets of LF were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). RP-related gene targets were retrieved through disease comprehensive databases. Protein-protein interaction (PPI) network of LF component-targets and RP disease-targets was constructed by STRING, and the intersection of the 2 networks was extracted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of theintersection network were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID). CytoHubba was used to screen the key targets. Results A total of 188 chemical constituents related to LF was retrieved from TCMSP database. 45 active ingredients were screened according to pharmacokinetic parameters oral bioavailability (OB) and drug similarity (DL). 36 active ingredients were further screened and 201 targets related to these constituents were obtained. 206 target genes directly related to RP were obtained from the disease comprehensive databases, and 89 genes were obtained from the intersection of component-target and disease-target PPI network. These genes were mainly involved in intracellular signal transduction, GTPase activity regulation, cell morphology regulation, and other biological processes. Molecular functions were mainly related to Rho guanine nucleotide exchange factor activity, GTPase activator activity, receptor signal protein serine/threonine kinase activity and so on. They were enriched in the cytoplasm, cell membrane, Golgi apparatus, and other regions. The mechanism was related to cell cycle pathways, neurotrophin signaling pathways, Ras signaling pathways, and so on. 10 key gene targets of LF in the treatment of RP were screened. Conclusions The material basis for LF to exert its pharmacodynamic effect is 36 active ingredients such as cycloartenol, mandenol, and so on. The key targets of LF in the treatment of RP include 10 genes, such as Rho, PAK, and so on. The main mechanism is related to the regulation of the Ras signaling pathway, neurotrophin signaling pathway, cell cycle related pathway, and other signaling networks.关键词
枸杞子/网络药理学/视网膜色素变性/分子机制/靶点/信号通路Key words
Network pharmacology/Retinitis pigmentosa/Lycii Fructus (Gou Qi Zi/枸杞子)/Molecular mechanism/Target/Signaling pathway引用本文复制引用
宋厚盼,彭清华,彭俊,曾梅艳,陈小娟,陈新怡,杨毅敬,周亚莎,田野,刘晓清,蔡雄..枸杞子治疗视网膜色素变性分子机制的网络药理学研究[J].数字中医药（英文）,2019,2(3):136-146,11.基金项目
We thank for the funding support from the National Natural Science Foundation of China (No. 81804150 and No. 81703920), Project funded by China Post-doctoral Science Foundation (No. 2019M662790), Natural Science Foundation of Hunan Province, China (No. 2019JJ50442 and No. 2019JJ40226), Research-based Learning and Innovative Experiment Program Project for Hunan University Students (No. 2017280), Scientific Research Project of Hunan Traditional Chinese Medicine Administration (No. 201780), Open Fund Project of Hunan Provincial Key Laboratory for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine (No. 2018YZD05), and Open Fund of the Domestic First-class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine (No. 2018ZYX20 and No. 2018ZYX26). （No. 81804150 and No. 81703920）
