摘要
旨在通过网络药理学和动物试验探究白术-肉苁蓉治疗便秘的效果和机制。通过TCMSP数据库获得白术-肉苁蓉成分及对应的靶点蛋白,借助GeneCards、OMIM等数据库得到便秘相关靶点。将基因整理导入UniProt数据库后利用Venny2.1.0、Cytoscape3.7.2和STRING绘制韦恩图及蛋白质-蛋白质相互作用(PPI)网络,并使用CentiScaPe 2.2插件进行分析。再通过DAVID数据库进行生物信息学GO分析及KEGG信号通路富集分析。通过AutodockTools和PyMOL等软件对部分核心靶点与潜在靶点较多的成分进行分子对接验证。将40只小鼠随机分为空白组(6只)和盐酸洛哌丁胺组(34只),分别用蒸馏水和10.0 mg·kg^(-1)盐酸洛哌丁胺灌胃。造模成功后,将30只便秘小鼠均分为模型组、阳性对照组和高、中、低剂量药物组。空白组和模型组蒸馏水灌胃,阳性对照组10.0 mg·kg^(-1)枸橼酸莫沙必利灌胃,高、中、低剂量药物组分别灌胃4.8、2.4、1.2 g·kg^(-1)的白术-肉苁蓉混悬液治疗,每日1次,持续7 d。7 d后进行排便和小肠运动试验。结果发现,PTGS 2为连接度最高的靶点基因,共筛选出AKT1、TNF和IL-6等19个白术-肉苁蓉治疗便秘的核心靶点,KEGG富集分析表明,脂质和动脉粥样硬化及乙型肝炎等通路较为关键。分子对接结果显示,白术-肉苁蓉潜在靶点较多的成分与便秘核心靶点结合较好。动物试验表明,与模型组比较,中、高剂量药物组首粒黑便时间显著缩短,小肠推进率显著增高。综上,白术-肉苁蓉可改善慢传输型便秘,多种活性成分可能通过PTGS2、AKT1、TNF和IL-6等关键靶点,调节多条信号通路治疗便秘。
The aim of this study was to explore the effect and mechanism of Atractylodes Macrocephala-Cistanche Deserticola on constipation through network pharmacology and animal experiments.The constituents and corresponding target proteins of Atractylodes Macrocephala-Cistanche Deserticola were obtained from TCMSP database,and constipation related targets were obtained from GeneCards,OMIM and other databases.After the genes were sorted into UniProt database,softwares including Venny2.1.0,Cytoscape3.7.2 and STRING were used to draw Venn diagram and protein-protein interaction(PPI)network,and then CentiScaPe 2.2 plug-in was used for analysis.Bioinformatics GO analysis and KEGG signaling pathway enrichment analysis were conducted through DAVID database.Some components with more potential targets and core targets were verified by molecular docking with AutodockTools and PyMOL.Forty mice were randomly divided into blank group(6 mice)and loperamide hydrochloride group(34 mice),which were gavaged with distilled water and 10.0 mg·kg^(-1) loperamide hydrochloride,respectively.After successful modeling,30 mice with constipation were evenly distributed divided into model group,positive control group and high-,medium-and low-dose drug groups.Blank group and model group were intragastric with distilled water,positive control group was intragastric with 10.0 mg·kg^(-1) moxapride citrate,and high-,medium-and low-dose groups were intragastric with 4.8,2.4 and 1.2 g·kg^(-1) Atractylodes Macrocephala-Cistanche Deserticola suspension,respectively,once a day for 7 days.Seven days later,the bowel movement and small bowel movement tests were performed.The results showed that PTGS 2 was the most highly connected target gene.A total of 19 core targets for the treatment of constipation including AKT1,TNF and IL-6 were screened out.KEGG enrichment analysis showed that lipid and atherosclerosis and hepatitis B pathways were more critical.Molecular docking results showed that the components with more potential targets in Atractylodes Macrocephala-Cistanche Deserticola had a good combination with the core targets of constipation.Animal experiments showed that compared with the model group,the time of first melena was significantly shortened and the small bowel propulsion rate was significantly increased in the medium-and high-dose drug groups.Atractylodes Macrocephala-Cistanche Deserticola can improve slow transit constipation.A variety of active ingredients may regulate multiple signaling pathways to treat constipation through key targets such as PTGS2,AKT1,TNF and IL-6.
作者
刘元红
胡玉欢
张莉
杨萍瑞
胡卫东
马琪
毕师诚
LIU Yuanhong;HU Yuhuan;ZHANG Li;YANG Pingrui;HU Weidong;MA Qi;BI Shicheng(College of Veterinary Medicine,Southwest University,Chongqing 402460,China;Institute of Chinese Veterinary Medicine,Southwest University,Chongqing 402460,China)
出处
《畜牧兽医学报》
CAS
CSCD
北大核心
2024年第2期834-845,共12页
ACTA VETERINARIA ET ZOOTECHNICA SINICA
基金
国家自然科学基金青年项目(32002325)。
关键词
网络药理学
白术-肉苁蓉
便秘
分子对接
作用机制
network pharmacology
Atractylodes Macrocephala-Cistanche Deserticola
constipation
molecular docking
mechanisms