基于网络药理学和实验验证的黄芪抗非酒精性脂肪肝作用机制探讨

IF 2 4区 医学 Q3 GASTROENTEROLOGY & HEPATOLOGY
Lili Fu, Zhongming Wu, Y. Chu, Wenbin Chen, Ling Gao, Shumin Mu, Jiajun Zhao
{"title":"基于网络药理学和实验验证的黄芪抗非酒精性脂肪肝作用机制探讨","authors":"Lili Fu, Zhongming Wu, Y. Chu, Wenbin Chen, Ling Gao, Shumin Mu, Jiajun Zhao","doi":"10.1155/2022/4745042","DOIUrl":null,"url":null,"abstract":"Objective Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.","PeriodicalId":12597,"journal":{"name":"Gastroenterology Research and Practice","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Explore the Mechanism of Astragalus mongholicus Bunge against Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Verification\",\"authors\":\"Lili Fu, Zhongming Wu, Y. Chu, Wenbin Chen, Ling Gao, Shumin Mu, Jiajun Zhao\",\"doi\":\"10.1155/2022/4745042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.\",\"PeriodicalId\":12597,\"journal\":{\"name\":\"Gastroenterology Research and Practice\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2022-04-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gastroenterology Research and Practice\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2022/4745042\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gastroenterology Research and Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/4745042","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 2

摘要

目的黄芪是一种在临床上广泛应用于治疗肝病的中药。然而,AMB治疗非酒精性脂肪性肝病(NAFLD)的疗效和机制尚不清楚。本研究的目的是基于网络药理学、分子对接和实验验证,系统地研究AMB对抗NAFLD的活性成分和机制。方法首先从中药系统药理学(TCMSP)数据库中筛选AMB的生物活性成分和相关靶标,从GeneCards数据库中获得NAFLD相关靶标。然后,利用STRING数据库构建AMB-NAFLD蛋白-靶标相互作用网络。使用DAVID数据库进行GO和KEGG途径富集分析。使用Cytoscape软件对成分靶标进行可视化。最后,通过分子对接和实验验证了网络药理学预测的结果。结果网络药理学预测槲皮素可能是AMB的主要活性成分,TNF和MAPK信号通路可能是AMB对抗NAFLD的关键靶点。分子对接验证结果表明,槲皮素作为AMB的主要活性成分,与TNF的结合亲和力最高。此外,通过体外实验,槲皮素在减轻NAFLD方面发挥了明显的作用。槲皮素上调AMPK磷酸化水平,抑制p-MAPK和TNF-α的表达。此外,我们进一步发现槲皮素可以增加PA诱导的HepG2细胞中ACC磷酸化和CPT1α的表达。结论槲皮素作为AMB的主要活性成分,通过调节AMPK/MAPK/TNF-α和AMPK/ACC/CPT1α信号通路发挥抗NAFLD作用,抑制炎症,减轻脂质积聚。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Explore the Mechanism of Astragalus mongholicus Bunge against Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Verification
Objective Astragalus mongholicus Bunge [Fabaceae] (AMB), a traditional Chinese medicine (TCM), has been widely used to treat liver diseases in the clinic. However, the efficacy and mechanism of AMB in the treatment of nonalcoholic fatty liver disease (NAFLD) remain unclear. The purpose of this study was to systematically investigate the active components and mechanisms of AMB against NAFLD based on network pharmacology, molecular docking, and experimental verification. Methods First, the bioactive components and relevant targets of AMB were screened from the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database, and NAFLD-related targets were obtained from the GeneCards database. Then, the AMB-NAFLD protein target interaction network was built by the STRING database. GO and KEGG pathway enrichment analyses were performed using the DAVID database. The component targets were visualized using Cytoscape software. Finally, molecular docking and experiments were used to verify the results of network pharmacological prediction. Results Network pharmacology predicted that quercetin may be the main active component in AMB, and the TNF and MAPK signaling pathways may be the key targets of AMB against NAFLD. Molecular docking validation results demonstrated that quercetin, as the main active component of AMB, had the highest binding affinity with TNF. Furthermore, quercetin played a distinct role in alleviating NAFLD through in vitro experiments. Quercetin upregulated the phosphorylation levels of AMPK and inhibited the expression of p-MAPK and TNF-α. In addition, we further discovered that quercetin could increase ACC phosphorylation and CPT1α expression in PA-induced HepG2 cells. Conclusions Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Gastroenterology Research and Practice
Gastroenterology Research and Practice GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
4.40
自引率
0.00%
发文量
91
审稿时长
1 months
期刊介绍: Gastroenterology Research and Practice is a peer-reviewed, Open Access journal which publishes original research articles, review articles and clinical studies based on all areas of gastroenterology, hepatology, pancreas and biliary, and related cancers. The journal welcomes submissions on the physiology, pathophysiology, etiology, diagnosis and therapy of gastrointestinal diseases. The aim of the journal is to provide cutting edge research related to the field of gastroenterology, as well as digestive diseases and disorders. Topics of interest include: Management of pancreatic diseases Third space endoscopy Endoscopic resection Therapeutic endoscopy Therapeutic endosonography.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信