石斛夜光丸治疗白内障的分子机制研究  

Study on the Molecular Mechanism of Shihu Yeguang Pill in Treating Cataract

作　　者：高丽煜 任瑞 丁敏[2,3] Gao Liyu;Ren Rui;Ding Min(School of Clinical Medicine,Weifang Medical University,Weifang 261053,China;Ophthalmologic Center,Affiliated Hospital of Weifang Medical University,Weifang 261053,China;Clinical Research Center,Afiliated Hospital of Weifang Medical University,Weifang 261053,China)

机构地区：[1]潍坊医学院临床医学院,山东潍坊261053 [2]潍坊医学院附属医院眼科中心,山东潍坊261053 [3]潍坊医学院附属医院临床医学研究中心,山东潍坊261053

出　　处：《南开大学学报（自然科学版）》2023年第2期67-76,共10页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：Supported by the Medical Research and Cultivation Foud of Affiliated Hospital of Weifang Medical University(2021wyfyzzjj02)。

摘　　要：白内障是常见的眼部疾病之一,多种因素都能导致白内障,它也是导致失明的首位原因.石斛夜光丸是古老而又常用的中成药之一.可治疗白内障、青光眼,久服有一定的疗效.然而,作用机制仍不清楚.在本研究中网络药理学,分子对接技术和细胞实验用来探索石斛夜光丸治疗白内障的分子机制.石斛夜光丸的活性成分和靶点通过中药系统药理学数据库与分析平台(TCMSP), PubChem, SuperPred和BATMAN-TCM数据库获得.与白内障相关的靶点来自GeneCards, CTD, DisGeNET, Malaccards和OMIM数据库以及通过Venny2.1.0获得了交集靶点.然后,使用Cytoscape软件构建了一个活性成分-靶点网络.通过String数据库和Cytoscape软件绘制了蛋白质-蛋白质相互作用(PPI)网络,获得核心靶点.接下来,通过Bioconduct平台得到KEGG通路富集分析.使用Autodock Vina进行分子对接,最后细胞实验验证石斛夜光丸的有效成分对H2O2引起的B-3细胞损伤的保护作用.结果表明,根据筛选标准,共筛选出1 511种石斛夜光丸活性成分和576个潜在靶点.通过在线数据库,确定了10 133个白内障相关靶点,获得了449个交集靶点.在活性成分-靶点网络中,异鼠李素、柚皮素和槲皮素是重要的活性成分.在PPI网络中,MAPK3, MAPK1, STAT3, TP53和AKT1是核心靶点.KEGG分析表明,石斛夜光丸治疗白内障的主要途径涉及PI3K-AKT,TNF和MAPK信号通路.在分子对接中,石斛夜光丸的活性化合物与核心靶点具有良好的亲和力.细胞存活实验表明,QUE,NAR和ISO可以改善H_(2)O_(2)诱导的B-3细胞损伤.对B-3细胞中总活性氧种类的测定表明,QUE, NAR和ISO能够保护H_(2)O_(2)引起的B-3细胞损伤,其机制为影响细胞凋亡以及减少细胞氧化反应.在本研究中,初步预测了石斛夜光丸治疗白内障的主要活性成分、靶点和信号通路,这将为进一步研究石斛夜光丸对白内障的保护机制和临床应用提供新的思路.Cataract is a common eye disease, which is caused by many reasons and is also the main cause of blindness. Shihu Yeguang Pill is one of the ancient and commonly used Chinese patent medicines. It has a certain curative effect in the treatment of cataracts and glaucoma. However, the action mechanism remains unclear. In this study, network pharmacology, molecular docking, and cell experiment were used to explore the underlying molecular mechanism of Shihu Yeguang Pill in treating cataracts. The active components and targets of Shihu Yeguang Pill were screened by TCMSP, PubChem, SuperPred, and BATMAN-TCM databases. The targets related to cataracts were obtained from GeneCards, CTD, Malacards, DisGeNET and OMIM database, and the intersected targets were obtained by Venny2.1.0. Then, an active component-target network was constructed using Cytoscape software. And the protein-protein interaction(PPI) network was drawn through the String database and Cytoscape software, and the core targets were obtained. Next, KEGG pathway enrichment analyses were performed by Bioconduct database. Molecular docking was conducted using Autodock Vina. Finally, cell experiments were conducted to verify the effect of active compounds. Results showed that according to the screening criteria, a total of 1 511 active compounds and 576 potential targets of Shihu Ye Guang Pill were chosen. Through the online database, 10 133 cataract-related targets were identified, and 449 overlapping targets were obtained. In an active component-target network, isorhamnetin, naringenin, and quercetin were the important active components. In the PPI network, MAPK3, MAPK1, STAT3, TP53, and AKT1 were the core targets. KEGG analyses showed that the main pathways of Shihu Yeguang Pill in treating cataracts involved PI3K-AKT, TNF, and MAPK signaling pathways. In molecular docking, the active compounds of Shihu Yeguang Pill had a good affinity with the core targets. Cell survival tests showed that QUE(quercetin), Naringenin(NAR), and ISO(Isorhamnetin) can improve B-3

关 键 词：石斛夜光丸 白内障 分子机制 网络药理 分子对接 

分 类 号：R963[医药卫生—微生物与生化药学]