摘要
目的基于网络药理学和分子对接研究枳壳改善非酒精性脂肪性肝病(NAFLD)的作用机制。方法以化合物的口服生物利用度(OB)和类药性(DL)为标准,采用中药系统药理学分析平台(TCMSP)、GeneCards、OMIM、TTD、DisGeNET等数据库,并结合课题组前期对枳壳成分分析研究,筛选枳壳主要活性成分及改善NAFLD的作用靶点。采用Cytoscape3.7.2软件构建中药-活性成分-靶点网络,采用STRING系统进行PPI网络分析提取核心网络,通过Metascape平台进行基因功能(GO)和通路注释(KEGG)富集分析。最后通过分子对接验证枳壳关键活性成分与核心靶点的作用特点。结果经筛选得到枳壳干预NAFLD的主要有效成分为β-谷甾醇、柚皮苷、川陈皮素、新橙皮苷;关键靶点为AKT1、TNF、TP53、CAT、JUN、MAPK8等;GO分析包括患者体内营养水平、氧化应激等;KEGG主要涉及NAFLD、AGE-RAGE、TNF等信号通路。分子对接结果显示,枳壳活性成分与核心靶点有较好的结合力。结论枳壳活性成分可通过多靶点、多通路发挥改善NAFLD的作用,其中主要涉及胰岛素抵抗、氧化应激和炎症反应等机制。
Objective To explore the mechanism of Aurantii Fructus on the treatment of non-alcoholic fatty liver disease(NAFLD) using the network pharmacology and molecular docking analysis. Methods Using the oral bioavailability(OB) and drug-like properties(DL) of the compounds as the standards, the main active ingredients of Aurantii Fructus were screened and analyzed using the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). The resulted data were further screened and analyzed using the GeneCards, OMIM,TTD, and DisGeNET for anti-non-alcoholic fatty liver disease activity-related genes. The software Cytoscape 3.7.2 was utilized to construct the drug-ingredient-target network and the STRING software was used to identify the core gene network and then analyzed their protein-protein interaction(PPI) network. After that, the Metascape tool was used to analyze the Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways, while the molecular docking was performed to verify characteristics of the key components and core targets of Fructus Aurantii. Results The main active ingredients of Aurantii Fructus in NAFLD intervention were β-sitosterol, naringenin, nobiletin, and neohesperidin. The key targets were AKT1, TNF, TP53, CAT, c-JUN, and MAPK8. The GO terms mainly included the nutrient levels, oxidoreductase activity, and etc., while the KEGG-enriched pathways were the NAFLD and AGE-RAGE signaling pathway in diabetic complications and TNF signaling pathway. The results of molecular docking showed that the active ingredients of Fructus Aurantii had a high affinity with the core targets. Conclusion The active ingredients of Aurantii Fructus in NAFLD treatment were to regulate multi-gene targets and pathways in the insulin resistance, oxidative stress, and inflammatory response.
作者
郑慧
王思为
蓝天
楼丽君
张峰
ZHENG Hui;WANG Si-wei;LAN Tian;LOU Li-jun;ZHANG Feng(Department of Pharmacy,The Quzhou Affiliated Hospital of Wenzhou Medical Uni-versity,Quzhou People's Hospital,Quzhou 324000,China;The Core Facility,The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People's Hospital,Quzhou 324000,China)
出处
《浙江中西医结合杂志》
2022年第2期116-121,共6页
Zhejiang Journal of Integrated Traditional Chinese and Western Medicine
基金
浙江省中医药科技计划项目(No.2021ZB328)
浙江省医药卫生科技计划项目(No.2019PY089)
浙江省衢州市科技计划竞争性分配项目(No.2018K20)。
关键词
网络药理学
枳壳
NAFLD
机制
Network Pharmacology
Aurantii fructus
NAFLD
molecular docking
作者简介
通信作者:张峰,Tel:0570-3055178,E-mail:felix.f.zhang@outlook.com。
