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Article(id=1210517373417820245, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1210517366081975259, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2022-0897, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1658332800000, receivedDateStr=2022-07-21, revisedDate=1662998400000, revisedDateStr=2022-09-13, acceptedDate=null, acceptedDateStr=null, onlineDate=1766539432147, onlineDateStr=2025-12-24, pubDate=1668182400000, pubDateStr=2022-11-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766539432147, onlineIssueDateStr=2025-12-24, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766539432147, creator=13701087609, updateTime=1766539432147, updator=13701087609, issue=Issue{id=1210517366081975259, tenantId=1146029695717560320, journalId=1189982191388893191, year='2022', volume='57', issue='11', pageStart='3259', pageEnd='3450', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1766539430399, creator=13701087609, updateTime=1766539608198, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1210518111875363690, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1210517366081975259, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1210518111875363691, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1210517366081975259, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=3345, endPage=3355, ext={EN=ArticleExt(id=1210517374139240550, articleId=1210517373417820245, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Mechanism of the anti-UC effect of Fructus Amomi based on network pharmacology, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

We predicted the anti-ulcerative colitis (UC) mechanism of Fructus Amomi based on network pharmacology. The anti-UC activity of Fructus Amomi were investigated by in vivo animal experiment, and the active components of Fructus Amomi were obtained through TCMSP, PubChem database and literature research. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Materia Medica of Chinese Academy of Medical Sciences. The potential targets of the active components and UC were predicted by SwissTargetPrediction, GeneCards and TTD databases. The protein-protein interaction (PPI) network was constructed by String database and Cytoscape software was used to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape platform. The molecular docking of key components and core targets was carried out by Sybyl X software. We screened out a total of 12 active components and 189 disease-component overlapping targets. Enrichment analyses obtained 227 related GO items and 168 signaling pathways. According to the results of molecular docking, most active components of Fructus Amomi showed good affinity with the JAKs receptor family. Furthermore, Western blot results verified that Fructus Amomi could effectively inhibit JAK/STAT signaling pathway, indicating that Fructus Amomi might exert the anti-UC activity by regulating JAK/STAT signaling pathway.

, correspAuthors=Hai-jing ZHANG, Lian-qiu WU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2022 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Chang-wei CHAI, Hai-jing ZHANG, Lian-qiu WU), CN=ArticleExt(id=1210517376743903555, articleId=1210517373417820245, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=基于网络药理学的砂仁抗溃疡性结肠炎机制研究, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

应用网络药理学方法预测砂仁抗溃疡性结肠炎(ulcerative colitis, UC) 的活性成分和作用机制。首先通过体内动物实验验证中药砂仁的抗UC活性, 动物福利和实验过程均遵循中国医学科学院药物研究所实验动物伦理委员会的规定。进一步应用TCMSP、PubChem数据库及文献调研获取砂仁的活性成分, 采用SwissTargetPrediction、GeneCards和TTD数据库预测活性成分抗UC的潜在作用靶点。使用String数据库构建蛋白互作关系网络; Cytoscape软件将成分-作用靶点网络可视化并进行拓扑学分析; Metascape平台进行GO功能和KEGG通路富集分析; Sybyl-X软件将砂仁关键活性成分与部分核心靶蛋白进行分子对接。筛选共获得12种活性成分、189个砂仁抗UC靶点, 富集分析后得到227个GO相关条目、168条相关信号通路。分子对接结果证明, 砂仁主要活性成分与JAK受体家族具有较好的亲和力, 体内验证结果表明砂仁能调控JAK/STAT信号通路。以上结果证明, 砂仁及其提取物可能通过JAK/STAT信号通路发挥抗UC作用。

, correspAuthors=张海婧, 吴练秋, authorNote=null, correspAuthorsNote=
*张海婧, E-mail: ;
吴练秋, Tel: 86-10-63031589, Fax: 86-10-63035779, E-mail:
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orderNo=5, keyword=JAK/STAT)], refs=[Reference(id=1210517384897630939, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/j.mayocp.2019.01.018, pmid=null, pmcid=null, year=2019, volume=94, issue=null, pageStart=1357, pageEnd=1373, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=null, journalName=Mayo Clin Proc, refType=null, unstructuredReference=Feuerstein JD, Moss AC, Farraye FA. Ulcerative colitis[J]. Mayo Clin Proc, 2019, 94: 1357-1373., articleTitle=Ulcerative colitis, refAbstract=null), Reference(id=1210517384981517022, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/j.disamonth.2019.02.004, pmid=null, pmcid=null, year=2019, volume=65, issue=null, pageStart=100851, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=null, journalName=Dis Mon, refType=null, unstructuredReference=Gajendran M, Loganathan P, Jimenez G, et al. A comprehensive review and update on ulcerative colitis[J]. Dis Mon, 2019, 65: 100851., articleTitle=A comprehensive review and update on ulcerative colitis, refAbstract=null), Reference(id=1210517385086374628, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/j.autrev.2019.03.002, pmid=null, pmcid=null, year=2019, volume=18, issue=null, pageStart=439, pageEnd=454, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=null, journalName=Autoimmun Rev, refType=null, unstructuredReference=Jeong DY, Kim S, Son MJ, et al. Induction and maintenance treatment of inflammatory bowel disease: a comprehensive review[J]. Autoimmun Rev, 2019, 18: 439-454., articleTitle=Induction and maintenance treatment of inflammatory bowel disease: a comprehensive review, refAbstract=null), Reference(id=1210517385178649321, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.2174/1381612826666200406081920, pmid=null, pmcid=null, year=2020, volume=26, issue=null, pageStart=2668, pageEnd=2675, url=null, language=null, rfNumber=[4], rfOrder=3, authorNames=null, journalName=Curr Pharm Des, refType=null, unstructuredReference=Alimohammadi N, Koosha F, Rafeian-Kopaei M. Current, new and future therapeutic targets in inflammatory bowel disease: a systematic review[J]. Curr Pharm Des, 2020, 26: 2668-2675., articleTitle=Current, new and future therapeutic targets in inflammatory bowel disease: a systematic review, refAbstract=null), Reference(id=1210517385279312621, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1093/ibd/izaa062, pmid=null, pmcid=null, year=2020, volume=26, issue=null, pageStart=1579, pageEnd=1587, url=null, language=null, rfNumber=[5], rfOrder=4, authorNames=null, journalName=Inflamm Bowel Dis, refType=null, unstructuredReference=Bertani L, Rossari F, Barberio B, et al. Novel prognostic biomarkers of mucosal healing in ulcerative colitis patients treated with anti-TNF: neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio[J]. Inflamm Bowel Dis, 2020, 26: 1579-1587., articleTitle=Novel prognostic biomarkers of mucosal healing in ulcerative colitis patients treated with anti-TNF: neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, refAbstract=null), Reference(id=1210517385384170226, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2020, volume=19, issue=null, pageStart=2650, pageEnd=2660, url=null, language=null, rfNumber=[6], rfOrder=5, authorNames=null, journalName=Exp Ther Med, refType=null, unstructuredReference=Chen HT, Huang HL, Xu HM, et al. Fecal microbiota transplantation ameliorates active ulcerative colitis[J]. Exp Ther Med, 2020, 19: 2650-2660., articleTitle=Fecal microbiota transplantation ameliorates active ulcerative colitis, refAbstract=null), Reference(id=1210517385463862005, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/S0140-6736(17)32448-0, pmid=null, pmcid=null, year=2017, volume=390, issue=null, pageStart=2769, pageEnd=2778, url=null, language=null, rfNumber=[7], rfOrder=6, authorNames=null, journalName=Lancet, refType=null, unstructuredReference=Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies[J]. Lancet, 2017, 390: 2769-2778., articleTitle=Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies, refAbstract=null), Reference(id=1210517385535165176, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1038/nrgastro.2015.150, pmid=null, pmcid=null, year=2015, volume=12, issue=null, pageStart=720, pageEnd=727, url=null, language=null, rfNumber=[8], rfOrder=7, authorNames=null, journalName=Nat Rev Gastroenterol Hepatol, refType=null, unstructuredReference=Kaplan GG. The global burden of IBD: from 2015 to 2025[J]. Nat Rev Gastroenterol Hepatol, 2015, 12: 720-727., articleTitle=The global burden of IBD: from 2015 to 2025, refAbstract=null), Reference(id=1210517385602274044, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2020, volume=101Suppl 1, issue=null, pageStart=2, pageEnd=15, url=null, language=null, rfNumber=[9], rfOrder=8, authorNames=null, journalName=Digestion, refType=null, unstructuredReference=Burri E, Maillard MH, Schoepfer AM, et al. Treatment algorithm for mild and moderate-to-severe ulcerative colitis: an update[J]. Digestion, 2020, 101Suppl 1: 2-15., articleTitle=Treatment algorithm for mild and moderate-to-severe ulcerative colitis: an update, refAbstract=null), Reference(id=1210517385656800000, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1126/science.aat7186, pmid=null, pmcid=null, year=2019, volume=363, issue=null, pageStart=993, pageEnd=998, url=null, language=null, rfNumber=[10], rfOrder=9, authorNames=null, journalName=Science, refType=null, unstructuredReference=Grootjans J, Krupka N, Hosomi S, et al. Epithelial endoplasmic reticulum stress orchestrates a protective IgA response[J]. Science, 2019, 363: 993-998., articleTitle=Epithelial endoplasmic reticulum stress orchestrates a protective IgA response, refAbstract=null), Reference(id=1210517385770046214, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2009, volume=25, issue=null, pageStart=869, pageEnd=null, url=null, language=null, rfNumber=[11], rfOrder=10, authorNames=null, journalName=J Changchun Univ Chin Med (长春中医药大学学报), refType=null, unstructuredReference=Li G. Traditional Chinese medicine treatment of gastric ulcer, chronic colitis in some cases[J]. J Changchun Univ Chin Med (长春中医药大学学报), 2009, 25: 869., articleTitle=Traditional Chinese medicine treatment of gastric ulcer, chronic colitis in some cases, refAbstract=null), Reference(id=1210517385862320906, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2010, volume=5, issue=null, pageStart=409, pageEnd=410, url=null, language=null, rfNumber=[12], rfOrder=11, authorNames=null, journalName=Med Inform (医学信息), refType=null, unstructuredReference=Ma D, Wang X. Experience of treating ulcerative colitis with traditional Chinese medicine[J]. Med Inform (医学信息), 2010, 5: 409-410., articleTitle=Experience of treating ulcerative colitis with traditional Chinese medicine, refAbstract=null), Reference(id=1210517387082863375, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/S0016-5085(98)70584-0, pmid=null, pmcid=null, year=1998, volume=114, issue=null, pageStart=706, pageEnd=713, url=null, language=null, rfNumber=[13], rfOrder=12, authorNames=null, journalName=Gastroenterology, refType=null, unstructuredReference=Pai R, Ohta M, Itani RM, et al. Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats[J]. Gastroenterology, 1998, 114: 706-713., articleTitle=Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats, refAbstract=null), Reference(id=1210517387221275409, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/S0378-8741(00)00398-6, pmid=null, pmcid=null, year=2001, volume=75, issue=null, pageStart=89, pageEnd=94, url=null, language=null, rfNumber=[14], rfOrder=13, authorNames=null, journalName=J Ethnopharmacol, refType=null, unstructuredReference=Jafri MA, Farah, Javed K, et al. Evaluation of the gastric antiulcerogenic effect of large cardamom (fruits of Amomum subulatum Roxb)[J]. J Ethnopharmacol, 2001, 75: 89-94., articleTitle=Evaluation of the gastric antiulcerogenic effect of large cardamom (fruits of Amomum subulatum Roxb), refAbstract=null), Reference(id=1210517387334521624, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/j.chroma.2011.06.041, pmid=null, pmcid=null, year=2011, volume=1218, issue=null, pageStart=7453, pageEnd=7475, url=null, language=null, rfNumber=[15], rfOrder=14, authorNames=null, journalName=J Chromatogr A, refType=null, unstructuredReference=Zhao J, Lv GP, Chen YW, et al. Advanced development in analysis of phytochemicals from medicine and food dual purposes plants used in China[J]. J Chromatogr A, 2011, 1218: 7453-7475., articleTitle=Advanced development in analysis of phytochemicals from medicine and food dual purposes plants used in China, refAbstract=null), Reference(id=1210517387435184924, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1039/C5FO00638D, pmid=null, pmcid=null, year=2015, volume=6, issue=null, pageStart=2803, pageEnd=2812, url=null, language=null, rfNumber=[16], rfOrder=15, authorNames=null, journalName=Food Funct, refType=null, unstructuredReference=Chien MY, Lin YT, Peng FC, et al. Gastroprotective potential against indomethacin and safety assessment of the homology of medicine and food formula cuttlebone complex[J]. Food Funct, 2015, 6: 2803-2812., articleTitle=Gastroprotective potential against indomethacin and safety assessment of the homology of medicine and food formula cuttlebone complex, refAbstract=null), Reference(id=1210517387581985569, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1038/299256a0, pmid=null, pmcid=null, year=1982, volume=299, issue=null, pageStart=256, pageEnd=259, url=null, language=null, rfNumber=[17], rfOrder=16, authorNames=null, journalName=Nature, refType=null, unstructuredReference=Manning DC, Snyder SH, Kachur JF, et al. Bradykinin receptor-mediated chloride secretion in intestinal function[J]. Nature, 1982, 299: 256-259., articleTitle=Bradykinin receptor-mediated chloride secretion in intestinal function, refAbstract=null), Reference(id=1210517387695231780, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=1983, volume=33, issue=null, pageStart=165, pageEnd=173, url=null, language=null, rfNumber=[18], rfOrder=17, authorNames=null, journalName=Jpn J Pharmacol, refType=null, unstructuredReference=Tsurumi K, Fujimura H. Effect of anti-inflammatory drugs on endotoxin-induced diarrhea in mice[J]. Jpn J Pharmacol, 1983, 33: 165-173., articleTitle=Effect of anti-inflammatory drugs on endotoxin-induced diarrhea in mice, refAbstract=null), Reference(id=1210517387808477993, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.4014/jmb.1605.05056, pmid=null, pmcid=null, year=2016, volume=26, issue=null, pageStart=2012, pageEnd=2018, url=null, language=null, rfNumber=[19], rfOrder=18, authorNames=null, journalName=J Microbiol Biotechnol, refType=null, unstructuredReference=Lee YG, Park JH, Jeon ES, et al. Fructus Amomi Cardamomi extract inhibit coxsackievirus-B3 induced myocarditis in murine myocarditis model[J]. J Microbiol Biotechnol, 2016, 26: 2012-2018., articleTitle=Fructus Amomi Cardamomi extract inhibit coxsackievirus-B3 induced myocarditis in murine myocarditis model, refAbstract=null), Reference(id=1210517387959472941, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1042/BSR20212681, pmid=null, pmcid=null, year=2022, volume=42, issue=null, pageStart=BSR20212681, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=19, authorNames=null, journalName=Biosci Rep, refType=null, unstructuredReference=Fan Y, Nguyen TV, Piao CH, et al. Fructus Amomi extract attenuates nasal inflammation by restoring Th1/Th2 balance and down-regulation of NF-κB phosphorylation in OVA-induced allergic rhinitis[J]. Biosci Rep, 2022, 42: BSR20212681., articleTitle=Fructus Amomi extract attenuates nasal inflammation by restoring Th1/Th2 balance and down-regulation of NF-κB phosphorylation in OVA-induced allergic rhinitis, refAbstract=null), Reference(id=1210517388068524846, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.3389/fphar.2017.00786, pmid=null, pmcid=null, year=2017, volume=8, issue=null, pageStart=786, pageEnd=null, url=null, language=null, rfNumber=[21], rfOrder=20, authorNames=null, journalName=Front Pharmacol, refType=null, unstructuredReference=Zhang T, Lu SH, Bi Q, et al. Volatile oil from Amomi Fructus attenuates 5-fluorouracil-induced intestinal mucositis[J]. Front Pharmacol, 2017, 8: 786., articleTitle=Volatile oil from Amomi Fructus attenuates 5-fluorouracil-induced intestinal mucositis, refAbstract=null), Reference(id=1210517388160799536, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.3390/molecules15107208, pmid=null, pmcid=null, year=2010, volume=15, issue=null, pageStart=7208, pageEnd=7217, url=null, language=null, rfNumber=[22], rfOrder=21, authorNames=null, journalName=Molecules, refType=null, unstructuredReference=Kim SJ, Kim MC, Um JY, et al. The beneficial effect of vanillic acid on ulcerative colitis[J]. Molecules, 2010, 15: 7208-7217., articleTitle=The beneficial effect of vanillic acid on ulcerative colitis, refAbstract=null), Reference(id=1210517388244685619, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1093/nar/gkz382, pmid=null, pmcid=null, year=2019, volume=47, issue=null, pageStart=W357, pageEnd=W364, url=null, language=null, rfNumber=[23], rfOrder=22, authorNames=null, journalName=Nucleic Acids Res, refType=null, unstructuredReference=Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Res, 2019, 47: W357-W364., articleTitle=SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules, refAbstract=null), Reference(id=1210517388341154615, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1093/bioinformatics/btt540, pmid=null, pmcid=null, year=2013, volume=29, issue=null, pageStart=3073, pageEnd=3079, url=null, language=null, rfNumber=[24], rfOrder=23, authorNames=null, journalName=Bioinformatics, refType=null, unstructuredReference=Gfeller D, Michielin O, Zoete V. Shaping the interaction landscape of bioactive molecules[J]. Bioinformatics, 2013, 29: 3073-3079., articleTitle=Shaping the interaction landscape of bioactive molecules, refAbstract=null), Reference(id=1210517388425040699, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2017, volume=2017, issue=null, pageStart=bax028, pageEnd=null, url=null, language=null, rfNumber=[25], rfOrder=24, authorNames=null, journalName=Database (Oxford), refType=null, unstructuredReference=Fishilevich S, Nudel R, Rappaport N, et al. GeneHancer: genome-wide integration of enhancers and target genes in GeneCards[J]. Database (Oxford), 2017, 2017: bax028., articleTitle=GeneHancer: genome-wide integration of enhancers and target genes in GeneCards, refAbstract=null), Reference(id=1210517388517315391, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1101/gr.1239303, pmid=null, pmcid=null, year=2003, volume=13, issue=null, pageStart=2498, pageEnd=2504, url=null, language=null, rfNumber=[26], rfOrder=25, authorNames=null, journalName=Genome Res, refType=null, unstructuredReference=Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13: 2498-2504., articleTitle=Cytoscape: a software environment for integrated models of biomolecular interaction networks, refAbstract=null), Reference(id=1210517388592812866, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1021/jm020406h, pmid=null, pmcid=null, year=2003, volume=46, issue=null, pageStart=499, pageEnd=511, url=null, language=null, rfNumber=[27], rfOrder=26, authorNames=null, journalName=J Med Chem, refType=null, unstructuredReference=Jain AN. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine[J]. J Med Chem, 2003, 46: 499-511., articleTitle=Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine, refAbstract=null), Reference(id=1210517388664116036, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1007/s12013-016-0735-8, pmid=null, pmcid=null, year=2016, volume=74, issue=null, pageStart=141, pageEnd=155, url=null, language=null, rfNumber=[28], rfOrder=27, authorNames=null, journalName=Cell Biochem Biophys, refType=null, unstructuredReference=Malathi K, Ramaiah S. Molecular docking and molecular dynamics studies to identify potential OXA-10 extended spectrum β-lactamase non-hydrolysing inhibitors for Pseudomonas aeruginosa[J]. Cell Biochem Biophys, 2016, 74: 141-155., articleTitle=Molecular docking and molecular dynamics studies to identify potential OXA-10 extended spectrum β-lactamase non-hydrolysing inhibitors for Pseudomonas aeruginosa, refAbstract=null), Reference(id=1210517388764779335, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1007/s40265-013-0176-2, pmid=null, pmcid=null, year=2014, volume=74, issue=null, pageStart=297, pageEnd=311, url=null, language=null, rfNumber=[29], rfOrder=28, authorNames=null, journalName=Drugs, refType=null, unstructuredReference=Mosli MH, Rivera-Nieves J, Feagan BG. T-cell trafficking and anti-adhesion strategies in inflammatory bowel disease: current and future prospects[J]. Drugs, 2014, 74: 297-311., articleTitle=T-cell trafficking and anti-adhesion strategies in inflammatory bowel disease: current and future prospects, refAbstract=null), Reference(id=1210517388844471114, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2022, volume=57, issue=null, pageStart=1282, pageEnd=1288, url=null, language=null, rfNumber=[30], rfOrder=29, authorNames=null, journalName=Acta Pharm Sin (药学学报), refType=null, unstructuredReference=Chai C, Zhang Y, Zhang H, et al. Emerging targets and drugs of inflammatory bowel disease[J]. Acta Pharm Sin (药学学报), 2022, 57: 1282-1288., articleTitle=Emerging targets and drugs of inflammatory bowel disease, refAbstract=null), Reference(id=1210517388932551502, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/j.phrs.2013.06.007, pmid=null, pmcid=null, year=2013, volume=76, issue=null, pageStart=1, pageEnd=8, url=null, language=null, rfNumber=[31], rfOrder=30, authorNames=null, journalName=Pharmacol Res, refType=null, unstructuredReference=Coskun M, Salem M, Pedersen J, et al. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease[J]. Pharmacol Res, 2013, 76: 1-8., articleTitle=Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease, refAbstract=null), Reference(id=1210517389003854672, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.3390/vaccines4010005, pmid=null, pmcid=null, year=2016, volume=4, issue=null, pageStart=5, pageEnd=null, url=null, language=null, rfNumber=[32], rfOrder=31, authorNames=null, journalName=Vaccines (Basel), refType=null, unstructuredReference=Zundler S, Neurath MF. Integrating immunologic signaling networks: the JAK/STAT pathway in colitis and colitis-associated cancer[J]. Vaccines (Basel), 2016, 4: 5., articleTitle=Integrating immunologic signaling networks: the JAK/STAT pathway in colitis and colitis-associated cancer, refAbstract=null), Reference(id=1210517389066769235, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1007/s00535-018-1449-z, pmid=null, pmcid=null, year=2018, volume=53, issue=null, pageStart=585, pageEnd=590, url=null, language=null, rfNumber=[33], rfOrder=32, authorNames=null, journalName=J Gastroenterol, refType=null, unstructuredReference=Verstockt B, Ferrante M, Vermeire S, et al. New treatment options for inflammatory bowel diseases[J]. J Gastroenterol, 2018, 53: 585-590., articleTitle=New treatment options for inflammatory bowel diseases, refAbstract=null), Reference(id=1210517389142266709, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1016/j.phymed.2021.153519, pmid=null, pmcid=null, year=2021, volume=84, issue=null, pageStart=153519, pageEnd=null, url=null, language=null, rfNumber=[34], rfOrder=33, authorNames=null, journalName=Phytomedicine, refType=null, unstructuredReference=Zhao Y, Luan H, Jiang H, et al. Gegen Qinlian decoction relieved DSS-induced ulcerative colitis in mice by modulating Th17/Treg cell homeostasis via suppressing IL-6/JAK2/STAT3 signaling[J]. Phytomedicine, 2021, 84: 153519., articleTitle=Gegen Qinlian decoction relieved DSS-induced ulcerative colitis in mice by modulating Th17/Treg cell homeostasis via suppressing IL-6/JAK2/STAT3 signaling, refAbstract=null), Reference(id=1210517389263901528, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1007/s10620-020-06611-w, pmid=null, pmcid=null, year=2021, volume=66, issue=null, pageStart=3002, pageEnd=3014, url=null, language=null, rfNumber=[35], rfOrder=34, authorNames=null, journalName=Dig Dis Sci, refType=null, unstructuredReference=Xiu MX, Liu YM, Chen GY, et al. Identifying hub genes, key pathways and immune cell infiltration characteristics in pediatric and adult ulcerative colitis by integrated bioinformatic analysis[J]. Dig Dis Sci, 2021, 66: 3002-3014., articleTitle=Identifying hub genes, key pathways and immune cell infiltration characteristics in pediatric and adult ulcerative colitis by integrated bioinformatic analysis, refAbstract=null), Reference(id=1210517389347787611, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.18632/oncotarget.14549, pmid=null, pmcid=null, year=2017, volume=8, issue=null, pageStart=22175, pageEnd=22186, url=null, language=null, rfNumber=[36], rfOrder=35, authorNames=null, journalName=Oncotarget, refType=null, unstructuredReference=Du L, Kim JJ, Shen J, et al. KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis[J]. Oncotarget, 2017, 8: 22175-22186., articleTitle=KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis, refAbstract=null), Reference(id=1210517389456839519, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.3748/wjg.v21.i36.10358, pmid=null, pmcid=null, year=2015, volume=21, issue=null, pageStart=10358, pageEnd=10366, url=null, language=null, rfNumber=[37], rfOrder=36, authorNames=null, journalName=World J Gastroenterol, refType=null, unstructuredReference=Volodko N, Salla M, Eksteen B, et al. TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development[J]. World J Gastroenterol, 2015, 21: 10358-10366., articleTitle=TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development, refAbstract=null), Reference(id=1210517389528142688, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2020, volume=2020, issue=null, pageStart=5217405, pageEnd=null, url=null, language=null, rfNumber=[38], rfOrder=37, authorNames=null, journalName=Biomed Res Int, refType=null, unstructuredReference=Wei M, Li H, Li Q, et al. Based on network pharmacology to explore the molecular targets and mechanisms of Gegen Qinlian Decoction for the treatment of ulcerative colitis[J]. Biomed Res Int, 2020, 2020: 5217405., articleTitle=Based on network pharmacology to explore the molecular targets and mechanisms of Gegen Qinlian Decoction for the treatment of ulcerative colitis, refAbstract=null), Reference(id=1210517389662360420, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1038/onc.2015.242, pmid=null, pmcid=null, year=2016, volume=35, issue=null, pageStart=2842, pageEnd=2851, url=null, language=null, rfNumber=[39], rfOrder=38, authorNames=null, journalName=Oncogene, refType=null, unstructuredReference=Joly AL, Deepti A, Seignez A, et al. The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development[J]. Oncogene, 2016, 35: 2842-2851., articleTitle=The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development, refAbstract=null), Reference(id=1210517389758829415, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.7150/thno.14882, pmid=null, pmcid=null, year=2016, volume=6, issue=null, pageStart=1324, pageEnd=1335, url=null, language=null, rfNumber=[40], rfOrder=39, authorNames=null, journalName=Theranostics, refType=null, unstructuredReference=Lin TY, Guo W, Long Q, et al. HSP90 inhibitor encapsulated photo-theranostic nanoparticles for synergistic combination cancer therapy[J]. Theranostics, 2016, 6: 1324-1335., articleTitle=HSP90 inhibitor encapsulated photo-theranostic nanoparticles for synergistic combination cancer therapy, refAbstract=null), Reference(id=1210517389830132584, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1097/01.MIB.0000442839.28664.75, pmid=null, pmcid=null, year=2014, volume=20, issue=null, pageStart=685, pageEnd=694, url=null, language=null, rfNumber=[41], rfOrder=40, authorNames=null, journalName=Inflamm Bowel Dis, refType=null, unstructuredReference=Collins CB, Strassheim D, Aherne CM, et al. Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-α and ameliorates murine intestinal inflammation[J]. Inflamm Bowel Dis, 2014, 20: 685-694., articleTitle=Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-α and ameliorates murine intestinal inflammation, refAbstract=null), Reference(id=1210517389918212972, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2014, volume=6, issue=null, pageStart=109, pageEnd=null, url=null, language=null, rfNumber=[42], rfOrder=41, authorNames=null, journalName=F1000Prime Rep, refType=null, unstructuredReference=Gonzalez-Cabrera PJ, Brown S, Studer SM, et al. S1P signaling: new therapies and opportunities[J]. F1000Prime Rep, 2014, 6: 109., articleTitle=S1P signaling: new therapies and opportunities, refAbstract=null), Reference(id=1210517389985321836, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=null, pmid=null, pmcid=null, year=2014, volume=7, issue=null, pageStart=205, pageEnd=214, url=null, language=null, rfNumber=[43], rfOrder=42, authorNames=null, journalName=Clin Exp Gastroenterol, refType=null, unstructuredReference=Degagné E, Saba JD. S1pping fire: sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer[J]. Clin Exp Gastroenterol, 2014, 7: 205-214., articleTitle=S1pping fire: sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer, refAbstract=null), Reference(id=1210517390048236399, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, doi=10.1021/jm401490p, pmid=null, pmcid=null, year=2014, volume=57, issue=null, pageStart=5023, pageEnd=5038, url=null, language=null, rfNumber=[44], rfOrder=43, authorNames=null, journalName=J Med Chem, refType=null, unstructuredReference=Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases[J]. 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A: Weight growth rate; B: Colon length; C: Disease activity index (DAI) score. <sup>##</sup><i>P</i> < 0.01 <i>vs</i> control; <sup>*</sup><i>P</i> < 0.05, <sup>**</sup> <i>P</i> < 0.01 <i>vs</i> model. SASP: Salazosulfapyridine (500 mg·kg<sup>-1</sup>); FA: Fructus Amomi (500 mg·kg<sup>-1</sup>); VA: Vanillic acid (200 mg·kg<sup>-1</sup>); BA: Bornyl acetate (10 mg·kg<sup>-1</sup>) , figureFileSmall=EtVO/p8vXoQNjJY4xxlqEA==, figureFileBig=dEf8Y9QEjIxDxVEzc/aoWQ==, tableContent=null), ArticleFig(id=1210517381001122365, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=F6j9DQ78uPEPmIR3iMLAOw==, figureFileBig=CdJMHrtlFq8ioJTU7m7QWw==, tableContent=null), ArticleFig(id=1210517381085008453, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 2, caption= Fructus Amomi and its extracts ameliorate pathological injury of colon tissue (HE, 200×) , figureFileSmall=F6j9DQ78uPEPmIR3iMLAOw==, figureFileBig=CdJMHrtlFq8ioJTU7m7QWw==, tableContent=null), ArticleFig(id=1210517381194060364, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=xukrjtePKy+biz3ybDBmhg==, figureFileBig=4y41pZYMQ+8aOBWJyKhNDw==, tableContent=null), ArticleFig(id=1210517381294723666, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 3, caption= Component-target network of Fructus Amomi , figureFileSmall=xukrjtePKy+biz3ybDBmhg==, figureFileBig=4y41pZYMQ+8aOBWJyKhNDw==, tableContent=null), ArticleFig(id=1210517382561403484, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=ZaIhTlran9PB6bnb1ZM+jA==, figureFileBig=4P8CFv6dag4Lzh+2xDbYeQ==, tableContent=null), ArticleFig(id=1210517382670455397, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 4, caption= Protein-protein interaction (PPI) network of Fructus Amomi , figureFileSmall=ZaIhTlran9PB6bnb1ZM+jA==, figureFileBig=4P8CFv6dag4Lzh+2xDbYeQ==, tableContent=null), ArticleFig(id=1210517382771118697, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=vYGWstPekoAvgXNnZ4NaAw==, figureFileBig=yr1jHJRydoomgwzdJHesWQ==, tableContent=null), ArticleFig(id=1210517382863393391, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 5, caption= The cluster generated from PPI network , figureFileSmall=vYGWstPekoAvgXNnZ4NaAw==, figureFileBig=yr1jHJRydoomgwzdJHesWQ==, tableContent=null), ArticleFig(id=1210517382972445305, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=uKJZQJ7SvrRKJzn4sVr1nA==, figureFileBig=dWDlxQzPVU2yeCyZm1NpgA==, tableContent=null), ArticleFig(id=1210517383068914303, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 6, caption= GO enrichment of the anti-UC effect of Fructus Amomi , figureFileSmall=uKJZQJ7SvrRKJzn4sVr1nA==, figureFileBig=dWDlxQzPVU2yeCyZm1NpgA==, tableContent=null), ArticleFig(id=1210517383173771910, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=WHE8QlUCd98+wP+wCI49oA==, figureFileBig=6PlzxYE+ksPFk7+KyFnbng==, tableContent=null), ArticleFig(id=1210517383295406734, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 7, caption= KEGG pathway enrichment of the anti-UC effect of Fructus Amomi , figureFileSmall=WHE8QlUCd98+wP+wCI49oA==, figureFileBig=6PlzxYE+ksPFk7+KyFnbng==, tableContent=null), ArticleFig(id=1210517383509316246, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=7gXhVYYW9dWfIl6pQz8GtA==, figureFileBig=aciybuyZWp8V7TgaR6XnZg==, tableContent=null), ArticleFig(id=1210517383601590939, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 8, caption= Schematic 3D representation that binding mode of S5 to JAK3 , figureFileSmall=7gXhVYYW9dWfIl6pQz8GtA==, figureFileBig=aciybuyZWp8V7TgaR6XnZg==, tableContent=null), ArticleFig(id=1210517383735808677, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=UbSFL8Q6V4ES+xUNlBGnjw==, figureFileBig=fTRPIEF/iWVBlCqEB88rHQ==, tableContent=null), ArticleFig(id=1210517383819694762, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Figure 9, caption= Effects of Fructus Amomi on the expression of JAK1 (A), p-STAT3 (B), STAT3 (C) in colon tissue detected by Western blot. <sup>#</sup><i>P</i> < 0.05, <sup>##</sup><i>P</i> < 0.01 <i>vs</i> control; <sup>*</sup><i>P</i> < 0.05 <i>vs</i> model , figureFileSmall=UbSFL8Q6V4ES+xUNlBGnjw==, figureFileBig=fTRPIEF/iWVBlCqEB88rHQ==, tableContent=null), ArticleFig(id=1210517383928746674, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Weight lossScoreStool consistencyScoreRectal bleedingScore
00Normal0Negative0
1%-5%1Loose stool2Occult blood and visual pellet bleeding2
5%-10%2Diarrhea4Gross bleeding and blood around anus4
10%-15%3
> 15%4
), ArticleFig(id=1210517384037798584, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Table 1, caption=

Disease activity index score

, figureFileSmall=null, figureFileBig=null, tableContent=
Weight lossScoreStool consistencyScoreRectal bleedingScore
00Normal0Negative0
1%-5%1Loose stool2Occult blood and visual pellet bleeding2
5%-10%2Diarrhea4Gross bleeding and blood around anus4
10%-15%3
> 15%4
), ArticleFig(id=1210517384146850494, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
NoMolecule nameMolecular formulaOB%DL
S1Stigmasta-5, 22-dien-3-beta-yl acetateC31H30O246.440.86
S2Icosa-11, 14, 17-trienoic acid methyl esterC21H36O244.810.23
S3StigmasterolC29H48O43.830.76
S4Sitosteryl acetateC31H52O240.390.85
S5Methyl icosa-11, 14-dienoateC21H38O239.670.23
S6Beta-sitosterolC29H50O36.910.75
S7Poriferast-5-en-3beta-olC29H50O36.910.75
S824-Ethylcholest-4-en-3-oneC29H48O36.080.76
S9(5S, 8S, 9S, 10R, 13R, 14S, 17R)-17-[(1R, 4R)-4-ethyl-1, 5-dimethylhexyl]-10, 13-dimethyl- 2, 4, 5, 7, 8, 9, 11, 12, 14, 15, 16, 17-dodecahydro-1H-cyclopenta[a]phenanthrene-3, 6-dioneC29H48O233.120.79
S10Vitamin-EC24H34N4O5S32.290.7
A1(+)-Bornyl acetateC12H20O265.550.08
A2Vanillic acidC8H8O435.470.04
), ArticleFig(id=1210517384239125185, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Table 2, caption=

Screened components of Fructus Amomi and their properties. OB: Oral bioavailability; DL: Drug-likeness

, figureFileSmall=null, figureFileBig=null, tableContent=
NoMolecule nameMolecular formulaOB%DL
S1Stigmasta-5, 22-dien-3-beta-yl acetateC31H30O246.440.86
S2Icosa-11, 14, 17-trienoic acid methyl esterC21H36O244.810.23
S3StigmasterolC29H48O43.830.76
S4Sitosteryl acetateC31H52O240.390.85
S5Methyl icosa-11, 14-dienoateC21H38O239.670.23
S6Beta-sitosterolC29H50O36.910.75
S7Poriferast-5-en-3beta-olC29H50O36.910.75
S824-Ethylcholest-4-en-3-oneC29H48O36.080.76
S9(5S, 8S, 9S, 10R, 13R, 14S, 17R)-17-[(1R, 4R)-4-ethyl-1, 5-dimethylhexyl]-10, 13-dimethyl- 2, 4, 5, 7, 8, 9, 11, 12, 14, 15, 16, 17-dodecahydro-1H-cyclopenta[a]phenanthrene-3, 6-dioneC29H48O233.120.79
S10Vitamin-EC24H34N4O5S32.290.7
A1(+)-Bornyl acetateC12H20O265.550.08
A2Vanillic acidC8H8O435.470.04
), ArticleFig(id=1210517384352371398, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
NameBetweenness centralityCloseness centralityDegree
STAT30.109 478 8580.537 162 16253
SRC0.124 805 6060.535 353 53552
TP530.146 604 0370.540 816 32750
EGFR0.063 9010.507 987 2245
HSP90AA10.073 291 6610.506 369 42745
MAPK30.049 670 8720.506 369 42740
MAPK10.044 242 7850.490 740 74139
PIK3CA0.022 154 3150.470 414 20138
PTPN110.033 650 1180.444 134 07835
JAK20.020 784 5340.450 424 92935
FYN0.015 483 7360.444 134 07831
LCK0.016 421 2090.434 426 2328
JAK10.004 022 6010.422 872 3428
ESR10.024 590 60.454 285 71428
PTK20.016 325 8440.449 152 54228
MAPK80.017 236 1910.466 275 6627
ERBB20.015 374 7990.464 912 28126
JAK30.017 598 4840.415 143 60325
RXRA0.067 368 7790.427 419 35525
MAPK140.020 786 7230.449 152 54224
), ArticleFig(id=1210517384465617611, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Table 3, caption=

Topological analysis of PPI network of Fructus Amomi

, figureFileSmall=null, figureFileBig=null, tableContent=
NameBetweenness centralityCloseness centralityDegree
STAT30.109 478 8580.537 162 16253
SRC0.124 805 6060.535 353 53552
TP530.146 604 0370.540 816 32750
EGFR0.063 9010.507 987 2245
HSP90AA10.073 291 6610.506 369 42745
MAPK30.049 670 8720.506 369 42740
MAPK10.044 242 7850.490 740 74139
PIK3CA0.022 154 3150.470 414 20138
PTPN110.033 650 1180.444 134 07835
JAK20.020 784 5340.450 424 92935
FYN0.015 483 7360.444 134 07831
LCK0.016 421 2090.434 426 2328
JAK10.004 022 6010.422 872 3428
ESR10.024 590 60.454 285 71428
PTK20.016 325 8440.449 152 54228
MAPK80.017 236 1910.466 275 6627
ERBB20.015 374 7990.464 912 28126
JAK30.017 598 4840.415 143 60325
RXRA0.067 368 7790.427 419 35525
MAPK140.020 786 7230.449 152 54224
), ArticleFig(id=1210517384562086607, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
TargetLigandTotal scorePMF scoreG scoreChem scoreC-score
JAK1S57.923 3-5.660 9-286.709 2-24.957 12
JAK1S107.137 4-24.135 7-249.344 7-22.029 54
JAK1S27.015 1-17.015 3-248.010 8-22.067 14
JAK1S46.256 726.617 3-257.228 5-13.1182
JAK1S76.004 8-2.969 3-212.346 9-17.887 32
JAK1S65.868 6-9.177 2-209.287-23.419 40
JAK1S15.757 9-1.940 9-240.281 3-18.195 62
JAK1S95.504 7-38.630 9-241.551 9-20.421 33
JAK1S35.472 2-37.676 8-229.022 7-18.450 83
JAK1S85.298 5-25.700 7-218.738 4-17.708 90
JAK1A23.987 5-40.789 8-171.261 1-17.513 44
JAK1A13.595-10.208 2-113.018 7-14.575 60
JAK2S27.784 311.861 7-219.521 9-21.539 83
JAK2S17.606 419.418 6-249.808 3-18.119 21
JAK2S47.585 821.307 7-264.688 5-18.444 53
JAK2S97.441 34.668 2-235.757 3-22.422 61
JAK2S56.585 713.111 7-249.712 5-19.795 23
JAK2S76.530 6-0.938 5-205.186 2-20.789 52
JAK2S66.332 7-1.326-225.954 9-20.261
JAK2S36.099 9-5.402 5-215.971 4-19.703 14
JAK2S105.9911.313-269.235 9-23.3374
JAK2S85.881 61.728 4-221.235 5-20.060 30
JAK2A23.965-11.689 8-122.875-15.335 71
JAK2A13.614 78.281 6-132.048 1-11.8711
JAK3S59.900 336.675 4-311.935 5-21.7393
JAK3S68.658 745.243 8-340.663 2-27.491 42
JAK3S88.395 729.670 5-320.302 1-28.864 70
JAK3S28.047 131.929 1-266.875 9-20.103 12
JAK3S107.418 9-3.563 1-275.625 2-25.949 44
JAK3S97.279 139.756 4-331.217 5-28.059 24
JAK3S77.030 644.184 8-350.593 4-26.845 33
JAK3S35.458 543.134 2-344.919 7-26.039 42
JAK3A24.857 5-10.844 9-121.608 9-18.873 20
JAK3A14.770 314.452 5-166.204 6-16.048 42
JAK3S44.303 865.334 5-368.223 9-25.212 24
JAK3S14.218 242.453 9-347.029 8-33.138 44
TYK2S28.216 439.870 4-304.033 7-23.348 83
TYK2S57.963 922.028 5-289.394 2-22.0883
TYK2S66.939 918.336 8-341.056 9-31.305 62
TYK2S96.439 114.523 8-310.728 6-29.1033
TYK2S16.218 736.765 4-361.079 3-27.115 53
TYK2S106.194 47.951 5-357.652 4-27.385 41
TYK2S85.35321.319 2-333.337-29.492 43
TYK2S45.351 221.405 7-263.349 3-22.047 63
TYK2A24.449 2-17.819-107.861 4-18.359 54
TYK2S74.365 519.205 4-323.621 8-28.901 74
TYK2S33.94511.409 9-236.644 8-25.249 64
TYK2A13.617 39.25-118.849 1-13.079 44
), ArticleFig(id=1210517384641778388, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1210517373417820245, language=CN, label=Table 4, caption=

Sybyl X scoring of the interaction between the potential active ingredients and JAKs

, figureFileSmall=null, figureFileBig=null, tableContent=
TargetLigandTotal scorePMF scoreG scoreChem scoreC-score
JAK1S57.923 3-5.660 9-286.709 2-24.957 12
JAK1S107.137 4-24.135 7-249.344 7-22.029 54
JAK1S27.015 1-17.015 3-248.010 8-22.067 14
JAK1S46.256 726.617 3-257.228 5-13.1182
JAK1S76.004 8-2.969 3-212.346 9-17.887 32
JAK1S65.868 6-9.177 2-209.287-23.419 40
JAK1S15.757 9-1.940 9-240.281 3-18.195 62
JAK1S95.504 7-38.630 9-241.551 9-20.421 33
JAK1S35.472 2-37.676 8-229.022 7-18.450 83
JAK1S85.298 5-25.700 7-218.738 4-17.708 90
JAK1A23.987 5-40.789 8-171.261 1-17.513 44
JAK1A13.595-10.208 2-113.018 7-14.575 60
JAK2S27.784 311.861 7-219.521 9-21.539 83
JAK2S17.606 419.418 6-249.808 3-18.119 21
JAK2S47.585 821.307 7-264.688 5-18.444 53
JAK2S97.441 34.668 2-235.757 3-22.422 61
JAK2S56.585 713.111 7-249.712 5-19.795 23
JAK2S76.530 6-0.938 5-205.186 2-20.789 52
JAK2S66.332 7-1.326-225.954 9-20.261
JAK2S36.099 9-5.402 5-215.971 4-19.703 14
JAK2S105.9911.313-269.235 9-23.3374
JAK2S85.881 61.728 4-221.235 5-20.060 30
JAK2A23.965-11.689 8-122.875-15.335 71
JAK2A13.614 78.281 6-132.048 1-11.8711
JAK3S59.900 336.675 4-311.935 5-21.7393
JAK3S68.658 745.243 8-340.663 2-27.491 42
JAK3S88.395 729.670 5-320.302 1-28.864 70
JAK3S28.047 131.929 1-266.875 9-20.103 12
JAK3S107.418 9-3.563 1-275.625 2-25.949 44
JAK3S97.279 139.756 4-331.217 5-28.059 24
JAK3S77.030 644.184 8-350.593 4-26.845 33
JAK3S35.458 543.134 2-344.919 7-26.039 42
JAK3A24.857 5-10.844 9-121.608 9-18.873 20
JAK3A14.770 314.452 5-166.204 6-16.048 42
JAK3S44.303 865.334 5-368.223 9-25.212 24
JAK3S14.218 242.453 9-347.029 8-33.138 44
TYK2S28.216 439.870 4-304.033 7-23.348 83
TYK2S57.963 922.028 5-289.394 2-22.0883
TYK2S66.939 918.336 8-341.056 9-31.305 62
TYK2S96.439 114.523 8-310.728 6-29.1033
TYK2S16.218 736.765 4-361.079 3-27.115 53
TYK2S106.194 47.951 5-357.652 4-27.385 41
TYK2S85.35321.319 2-333.337-29.492 43
TYK2S45.351 221.405 7-263.349 3-22.047 63
TYK2A24.449 2-17.819-107.861 4-18.359 54
TYK2S74.365 519.205 4-323.621 8-28.901 74
TYK2S33.94511.409 9-236.644 8-25.249 64
TYK2A13.617 39.25-118.849 1-13.079 44
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基于网络药理学的砂仁抗溃疡性结肠炎机制研究
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柴常伟 , 张海婧 * , 吴练秋 *
药学学报 | 研究论文 2022,57(11): 3345-3355
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药学学报 | 研究论文 2022, 57(11): 3345-3355
基于网络药理学的砂仁抗溃疡性结肠炎机制研究
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柴常伟, 张海婧* , 吴练秋*
作者信息
  • 中国医学科学院、北京协和医学院药物研究所, 北京 100050

通讯作者:

*张海婧, E-mail: ;
吴练秋, Tel: 86-10-63031589, Fax: 86-10-63035779, E-mail:
Mechanism of the anti-UC effect of Fructus Amomi based on network pharmacology
Chang-wei CHAI, Hai-jing ZHANG* , Lian-qiu WU*
Affiliations
  • Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
出版时间: 2022-11-12 doi: 10.16438/j.0513-4870.2022-0897
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摘要
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应用网络药理学方法预测砂仁抗溃疡性结肠炎(ulcerative colitis, UC) 的活性成分和作用机制。首先通过体内动物实验验证中药砂仁的抗UC活性, 动物福利和实验过程均遵循中国医学科学院药物研究所实验动物伦理委员会的规定。进一步应用TCMSP、PubChem数据库及文献调研获取砂仁的活性成分, 采用SwissTargetPrediction、GeneCards和TTD数据库预测活性成分抗UC的潜在作用靶点。使用String数据库构建蛋白互作关系网络; Cytoscape软件将成分-作用靶点网络可视化并进行拓扑学分析; Metascape平台进行GO功能和KEGG通路富集分析; Sybyl-X软件将砂仁关键活性成分与部分核心靶蛋白进行分子对接。筛选共获得12种活性成分、189个砂仁抗UC靶点, 富集分析后得到227个GO相关条目、168条相关信号通路。分子对接结果证明, 砂仁主要活性成分与JAK受体家族具有较好的亲和力, 体内验证结果表明砂仁能调控JAK/STAT信号通路。以上结果证明, 砂仁及其提取物可能通过JAK/STAT信号通路发挥抗UC作用。

砂仁  /  溃疡性结肠炎  /  网络药理学  /  作用机制  /  JAK/STAT

We predicted the anti-ulcerative colitis (UC) mechanism of Fructus Amomi based on network pharmacology. The anti-UC activity of Fructus Amomi were investigated by in vivo animal experiment, and the active components of Fructus Amomi were obtained through TCMSP, PubChem database and literature research. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Materia Medica of Chinese Academy of Medical Sciences. The potential targets of the active components and UC were predicted by SwissTargetPrediction, GeneCards and TTD databases. The protein-protein interaction (PPI) network was constructed by String database and Cytoscape software was used to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape platform. The molecular docking of key components and core targets was carried out by Sybyl X software. We screened out a total of 12 active components and 189 disease-component overlapping targets. Enrichment analyses obtained 227 related GO items and 168 signaling pathways. According to the results of molecular docking, most active components of Fructus Amomi showed good affinity with the JAKs receptor family. Furthermore, Western blot results verified that Fructus Amomi could effectively inhibit JAK/STAT signaling pathway, indicating that Fructus Amomi might exert the anti-UC activity by regulating JAK/STAT signaling pathway.

Fructus Amomi  /  ulcerative colitis  /  network pharmacology  /  action mechanism  /  JAK/STAT
柴常伟, 张海婧, 吴练秋. 基于网络药理学的砂仁抗溃疡性结肠炎机制研究. 药学学报, 2022 , 57 (11) : 3345 -3355 . DOI: 10.16438/j.0513-4870.2022-0897
Chang-wei CHAI, Hai-jing ZHANG, Lian-qiu WU. Mechanism of the anti-UC effect of Fructus Amomi based on network pharmacology[J]. Acta Pharmaceutica Sinica, 2022 , 57 (11) : 3345 -3355 . DOI: 10.16438/j.0513-4870.2022-0897
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溃疡性结肠炎(ulcerative colitis, UC) 是一种慢性、免疫系统介导的肠道炎症, 属于炎症性肠病(inflammatory bowel disease, IBD) 的一种。UC首先累及结肠, 并向近端结肠发展。临床表现主要有体重降低、腹泻、腹痛、黏液血便等, 病变反复发作。由于该病病程较长, 延绵不愈, 极大影响患者的生活质量, 长期反复进展的UC甚至可转化为结肠炎相关的结肠癌, 严重危害患者生活质量和生命健康[1-3]。近年来, 随着人们生活习惯、饮食方式和工作压力等因素改变, 我国UC的发病率呈逐年上升趋势[4-6], 在过去的几十年中, 由于患病人数的空前增加[7], UC已经成为全球性的公共卫生健康挑战, 对公共健康系统造成了严重的经济和资源负担[8]。
UC临床上以内科治疗为主, 常用的治疗药物包括5-氨基水杨酸类、糖皮质激素类、免疫抑制剂等, 但这些药物存在疗效不理想、不良反应多等缺点。目前药物研发的热点主要包括抗肿瘤坏死因子单克隆抗体(如阿达木单抗) 在内的生物制剂, 该类药物较小分子药物更为有效, 但生物制剂存在价格昂贵、潜在的免疫排斥反应、储存要求高和应用后耐药等缺点[9, 10]。因此, 寻找高效低毒的抗UC药物并阐明其作用机制是亟待解决的关键问题。
砂仁(Fructus Amomi) 是姜科植物阳春砂、绿壳砂或海南砂的干燥成熟果实。在中医理论中, 砂仁性温味辛, 归脾、胃、肾经, 功能主治为湿浊中阻、脘痞不饥、脾胃虚寒、呕吐泄泻、妊娠恶阻、胎动不安, 具有化湿开胃、温脾止泻、理气安胎等多种功效, 被广泛用于治疗胃肠道疾病[11, 12]。现代药理学证明砂仁具有多种生物学活性: ①胃肠道保护作用: 砂仁挥发油能显著降低胃液、胃酸、胃泌素分泌和胃蛋白酶活性, 抑制细菌增殖, 保护胃肠道黏膜[13], 并具有直接保护胃黏膜屏障的作用[14, 15]; 砂仁精油能促进胃排空, 调节胃肠道菌群从而保护胃肠道[16]; ②抗菌活性: 砂仁的石油醚和乙醚提取物均有抗革兰阳性菌和革兰阴性菌的活性[17, 18]; ③抗炎活性: 砂仁提取物具有显著的抗炎活性, 能够抑制病毒诱导的小鼠心肌炎[19], 还有文献[20]报道砂仁提取物能够改善卵清蛋白(ovalbumin, OVA) 诱导的过敏性鼻炎; 砂仁的水提物和挥发油能明显改善5-氟尿嘧啶诱导的肠黏膜炎症[21]。
基于中药砂仁的胃肠道保护、抗菌和抗炎功能, 本文通过网络药理学和实验验证结合的方法, 通过口服生物利用度(oral bioavailability, OB) 及类药性(drug-likeness, DL) 筛选获得砂仁潜在活性成分, 同时预测其活性成分的潜在抗UC靶点。在此基础上构建“成分-靶点”网络图, 挖掘潜在活性成分的抗UC核心靶点并预测作用机制, 最后运用分子对接和动物实验验证砂仁活性成分抗UC机制, 为进一步挖掘砂仁抗UC有效成分和作用机制提供参考。
材料与方法
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数据库及软件  中药系统药理学数据库TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform http//lsp.nwu.edu.cn/tcmsp.php/), SwissTargetPrediction数据库蛋白质数据库(http://www.swisstargetprediction.ch/), Pubchem化学小分子数据库(http://pubchem.ncbi.nlm.nih.gov/), GeneCards基因组注释数据库平台(http://www.genecards.org/), TTD疾病靶点数据库(http://db.idrblab.net/ttd/), STRING蛋白质相互作用信息数据库(https://string-ilh.org/), Metascape基因富集分析数据库(http://metascape.org/), RCSB PDB蛋白质结构数据库(http://www.rscb.org/), 网络可视化分析软件Cytoscape (Version 3.9.1), Sybyl X (Version2.1.1)。
实验动物  36只C57BL/6J小鼠(20~22 g), 雄性, SPF级, 购自北京华阜康生物科技股份有限公司; 许可证号: SYXK (京) 2019-0023。饲养于中国医学科学院药物研究所动物房, 温度25 ℃, 湿度40%, 每12 h明暗交替循环饲养。所有动物实验按照中国医学科学院药物研究所动物伦理委员会相关规定执行。
试剂与仪器  中药砂仁(广东私养家健康科技有限公司, 批号: 220201 A01); 柳氮磺吡啶肠溶片(上海信谊天平药业有限公司, 批号: 09200811); 乙酸龙脑酯(纯度≥ 97%, MedChemExpress公司, 货号: HY-N0756); 香草酸(纯度≥ 98%, 北京倍特仁康生物医药科技有限公司, 货号: BT-CQ12-100 mg); 右旋葡聚糖硫酸钠(DSS, 相对分子质量: 35 000~36 000, MP Biomedicals公司, 批号: S7102)。JAK1 (the Janus kinase 1)、p-STAT3 (phosphorylated signal transducer and activator of transcription 3) 抗体(美国Cell Signaling Technology公司, 货号: 3344T、9145T); 信号转导和转录激活因子3 (signal transducer and activator of transcription 3, STAT3, 美国Abcam公司, 货号: ab68153); 兔抗3-磷酸甘油醛脱氢酶(glyceraldehyde-3-phosphate dehydrogenase, GAPDH) 及山羊抗兔IgG (博奥瑞京北京科技发展有限公司, 货号Ab1029t和S8001); Western blot试剂盒(北京聚德安泰科技有限公司, 货号: JD107)。超净工作台(北京东联哈尔仪器制造有限公司, 型号: DJ-CJ-2ND); 低温离心机(日本久保田公司, 型号: K21128-F000); 一体式化学发光成像仪(上海勤翔科学仪器有限公司, 型号: ChemiScope S6)。
体内活性验证  小鼠适应性饲养7天后随机分为6组: 正常组、模型组、柳氮磺吡啶组(SASP)、砂仁组(Fructus Amomi)、乙酸龙脑酯组(bornyl acetate) 和香草酸组(vanillic acid), 每组6只。使用粉碎机将砂仁药材高速研磨成细粉, 精密称取500 mg细粉溶于10 mL蒸馏水中制成砂仁粉末水溶液; 将10 mg乙酸龙脑酯溶于10 mL蒸馏水中制成乙酸龙脑酯混悬液; 将200 mg香草酸溶于10 mL蒸馏水中制成香草酸水溶液。除正常组外, 其余各组小鼠均给予3% DSS溶液自由饮用, 连续7天, 正常组给予正常饮用水。自造模第1天开始, 各给药组开始灌胃给药, SASP组小鼠每天给予500 mg·kg-1柳氮磺吡啶水溶液, 砂仁组小鼠每天给予500 mg·kg-1砂仁粉末水溶液, 乙酸龙脑酯组每天给予10 mg·kg-1乙酸龙脑酯混悬液[21], 香草酸组每天给予200 mg·kg-1香草酸水溶液[22]。终止实验, 处死各组动物, 并检测结肠炎各项指标, 进行疾病活动指数(disease activity index, DAI)评分(标准见表 1), 综合评价化合物的抗UC药效学活性。
潜在活性组分数据库的构建  通过TCMSP数据库检索砂仁化学成分, 并结合Pubmed数据库中已报道的砂仁相关文献, 构建砂仁成分数据库。按OB ≥ 30%, DL ≥ 0.18为条件进行初步筛选, 得到砂仁的潜在活性成分10个, 结合动物实验和文献检索结果, 本研究选取乙酸龙脑酯和香草酸也作为其潜在活性成分。最后, 应用Pubchem数据库获取潜在活性成分的化学结构, 构建砂仁的潜在活性成分数据库。
“成分-靶点”互作网络的构建  将检索得到的砂仁中主要化合物的SMILES导入SwissTargetPrediction数据库[23, 24]进行靶点预测, 筛选probability > 0.1的可能靶点。同时以“ulcerative colitis”为关键词, 通过GeneCards数据库[25]和TTD数据库检索UC相关的疾病靶蛋白。将上述数据库获取的相关疾病靶点与SwissTarget-Prediction预测得到的砂仁主要化合物潜在作用靶点取交集作为砂仁治疗UC的潜在作用靶点进行机制探讨。为明确砂仁中各活性成分、靶点和疾病之间的关系, 将筛选得到的共有靶点与活性化合物对应关系导入Cytoscape 3.9.1软件, 构建“成分-靶点”可视化网络图。采用Network Analyzer工具进行拓扑分析, 对砂仁抗UC的“成分-靶点”网络的连接度(degree) 进行研究。
蛋白相互作用网络的构建及GO和KEGG富集分析  为进一步分析砂仁抗UC潜在作用靶点的功能和作用机制, 将筛选得到的共有靶点导入STRING数据库[26], 选取打分值大于0.7 (高置信度) 作为过滤器。利用Cytoscape 3.9.1软件构建蛋白-蛋白相互作用(protein-protein interaction, PPI) 网络并采用拓扑学分析各网络节点的介度、紧密度及连接度, 遴选砂仁治疗UC的核心蛋白。将共有靶点数据导入Metascape数据库进行GO和KEGG通路富集分析。
分子对接验证  将筛选得到的砂仁潜在活性成分化学结构转为sdf格式, 本研究使用Sybyl X 2.1软件[27]的surflex-dock程序, 首先使用去除配体分子水分子、修复残基和加氢等标准过程定义受体蛋白结构, 然后生成蛋白结合口袋, 与潜在活性成分靶点进行对接, 得到配体和蛋白分子对接评分[28]。
Western blot法检测结肠组织中JAK1、p-STAT3和STAT3的表达  取小鼠结肠样本通过匀浆制备样品, 用含有蛋白酶抑制剂和磷酸酶抑制剂的RIPA裂解液提取蛋白, 采用BCA法测定蛋白浓度并定量, 加热法进行蛋白变性; 制备10% SDS-PAGE凝胶, 上样后进行电泳、转膜、封闭, 4 ℃过夜孵育JAK1 (1∶1 000)、p-STAT3 (1∶1 000)、STAT3 (1∶1 000) 及GAPDH (1∶5 000) 一抗, 次日用辣根过氧化物酶(HRP) 标记的兔二抗(1∶5 000) 室温孵育1 h后洗膜并显影; 利用Image J软件分析条带灰度值, 以各组目的蛋白条带与各组内参GAPDH条带的灰度值比值作为该蛋白的相对表达量并进行统计分析。
统计学方法  使用GraphPad Prism 8.3.0软件进行数据分析, 实验结果以$ \overline{x} $ ± s表示。两组间统计学差异采用unpaired t test方法分析。P < 0.05表示具有统计学差异。
结果
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1 砂仁抗UC活性药效学验证
为了考察中药砂仁的抗UC活性, 本研究构建了DSS诱导的小鼠UC模型用于评价中药砂仁粉末及其提取物乙酸龙脑酯和香草酸的抗UC活性。通过小鼠体重变化率、结肠长度和小鼠疾病活动指数考察砂仁及其提取物的抗UC活性。实验结果表明, 砂仁粉末溶液、乙酸龙脑酯和香草酸均能显著改善UC小鼠体重下降的症状; 香草酸能够显著改善UC小鼠结肠挛缩的症状; 砂仁粉末溶液、乙酸龙脑酯和香草酸在一定程度上均能降低小鼠的DAI评分(图 1)。此外, 砂仁和香草酸能明显改善UC小鼠的结肠病理损伤(图 2)。综上所述, 砂仁及其提取物具有较好的抗UC活性。
2 砂仁活性成分筛选及靶点预测
通过TCMSP数据库结合Pubmed数据库文献检索, 得到砂仁的化学组分165种, 通过对这些化合物进行口服生物利用度及类药性筛选, 最后获得10个砂仁潜在活性成分(S1~S10), 根据体内实验结果和文献检索[20, 22], 本研究选取乙酸龙脑酯(A1) 和香草酸(A2) 也作为其潜在活性成分。潜在活性成分的编号、名称、分子式及性质见表 2。应用SwissTargetPrediction数据库预测砂仁12种潜在活性成分的靶点, 去除重复靶点后共获得化合物对应靶点189个。通过GeneCards数据库和TTD数据库检索得到的UC相关靶点4 848个, 两个靶点数据库取交集后最终获得189个砂仁中潜在活性成分的抗UC靶点。
3 砂仁抗UC“成分-靶点”和靶点蛋白互作网络构建及分析
为了探究砂仁中潜在活性成分的抗UC机制, 将12个活性成分和189个靶点的“成分-靶点”对应关系导入Cytoscape软件, 构建砂仁活性成分抗UC“成分-靶点”网络图(图 3), 绿色节点表示活性成分, 蓝色节点表示砂仁活性成分与UC疾病靶点的共有靶点。然后将共有靶点导入String数据库构建PPI网络图。该网络(图 4) 共包括节点189个、边859条、平均节点度值为9.09、平均介数为0.456。拓扑分析结果显示, 度值较高的靶蛋白包括STAT3、非受体酪氨酸激酶(SRC proto-oncogene, SRC)、肿瘤蛋白p53 (tumor protein p53, TP53)、表皮生长因子受体(epidermal growth factor receptor, EGFR)、热休克蛋白90α (heat shock protein 90 alpha family class A member 1, HSP90AA1) 等, 度值前20的靶点见表 3, 其中包含JAK1、JAK2、JAK3和STAT3四个靶点, 且具有较高的度值, 进一步使用cluster.viz插件对PPI网络进行聚类分析, 得到连接度更高的亚网络(图 5), 其中也包含JAK2和STAT3两个靶点, 这表明JAK/STAT信号通路可能在砂仁治疗UC的过程中发挥重要作用。
4 砂仁抗UC靶点GO通路富集分析
通过Metascape数据库对189个砂仁抗UC的潜在靶点进行GO富集分析(P < 0.01), 共得到227个条目, 包括197个生物过程(biological processes, BP), 3种细胞组分(cellular components, CC), 27种分子功能(molecular functions, MP), 根据P值筛选出每部分的前10个条目(图 6), 结果表明, 砂仁抗UC涉及多个生物学过程, 影响多种细胞组分和分子功能, 如蛋白磷酸化、激素反应、蛋白激酶活性、蛋白丝氨酸/苏氨酸/酪氨酸激酶活性等。
5 砂仁抗UC靶点KEGG通路富集分析
在KEGG富集分析中共获得168条相关信号通路(P < 0.01), 根据P值的大小结果制作的相关信号通路气泡图显示砂仁抗UC涉及疾病信号通路(pathways in cancer、endocrine resistance、EGFR tyrosine kinase inhibitor resistance)、信号转导信号通路(PI3K/AKT signaling pathway)、免疫信号通路(sphingolipid signaling pathway、chemokine signaling pathway) 等(图 7), 其中鞘磷脂信号通路(sphingolipid signaling pathway) 在淋巴细胞迁移促进肠道炎症发生过程中发挥关键作用, 通路中的鞘氨醇-1-磷脂受体(sphingosine 1-phosphate receptor, S1PR) 已经成为UC治疗的新兴药物靶点[29, 30]; JAK/STAT信号通路是趋化因子信号通路(chemokine signaling pathway) 中的重要分支, 该通路能转导多种促炎细胞因子信号, JAK/STAT信号通路还能调节效应T细胞和调节性T细胞(regulatory T cell, Treg) 的平衡并促进肠上皮细胞和髓系细胞的免疫功能, 以此参与UC的发病过程[31, 32]。因此, 靶向JAK激酶(Janus kinases) 的抑制剂也是抗UC药物研发的热点方向, 其中JAK激酶的非选择性小分子抑制剂托法替布(tofacitinib) 在临床上用于UC的治疗[33]。结合PPI网络聚类分析图中核心靶点和KEGG通路富集结果, 本课题组预测砂仁可能是通过抑制JAK/STAT信号通路发挥抗UC作用。
6 分子对接
砂仁抗UC靶点PPI网络分析和KEGG通路富集分析结果表明, 砂仁的抗UC活性与JAK/STAT信号通路相关。为了进一步探究砂仁中活性成分的抗UC机制, 本研究对活性成分与JAK激酶进行了分子对接。使用Sybyl X软件的分子对接模块, 对活性成分与4种JAK家族激酶进行了半柔性对接, 结果如表 4所示, 其中对接得分(total score) 是以-lg为单位的模拟结合能, 能反映配体与受体的结合亲合力, 综合考虑了极性作用、疏水作用等因素, 用对接得分来评价分子对接结果: 得分值越大, 配体与受体结合越稳定, 越有可能存在相互作用。对接分数 > 7分, 说明配体分子与靶点可能存在强的结合, 对接分数 > 5分说明配体分子与靶点可能存在较好的结合[27]。结果显示, 砂仁中的潜在活性成分与JAK1、JAK2、JAK3和TYK2 (tyrosine kinase 2) 共有14对相互作用评分大于7, 其中S5化合物与JAK3靶点的结合评分更是达到了9.9分(图 8), 表明砂仁的潜在活性成分可能与JAK激酶之间存在强相互作用, 从而发挥抗UC活性。
7 砂仁及其提取物对JAK/STAT通路的作用
为了验证砂仁抗UC的分子机制, 本研究考察了砂仁及其提取物对UC小鼠结肠组织JAK/STAT通路的影响, Western blot结果显示, UC小鼠结肠中JAK1的表达增加并且STAT3的磷酸化过程增强, 砂仁和其提取物香草酸能明显抑制UC小鼠结肠组织中JAK1的表达和STAT3磷酸化(图 9), 目前已有文献[34]报道中药方剂提取物通过抑制JAK/STAT信号通路发挥抗UC作用, 因此, 砂仁及其提取物可通过抑制JAK/STAT信号通路发挥抗UC作用。
讨论
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砂仁是我国药食两用的传统中药材, 含有挥发油、黄酮等多种活性成分, 具有抗氧化、抗菌等活性。本文通过文献检索和实验验证, 证明砂仁及其提取物具有较好的抗结肠炎活性。考虑到中药材多成分、多靶点的特点, 本研究采用网络药理学结合实验验证的方法对砂仁中的潜在活性成分进行了抗UC机制研究。
根据PPI网络预测的砂仁关键活性成分抗UC的关键靶点包括STAT3、SRC、TP53、EGFR、HSP90AA1等, STAT3是一种转录因子, 参与调控细胞的增殖、凋亡和癌变过程, 其磷酸化后参与的JAK/STAT通路在炎症信号转导过程中发挥关键作用[31]。SRC是一种非受体酪氨酸激酶, 它能够激活NF-κB信号通路从而引起DSS诱导的大鼠肠道组织的持续损伤, 抑制SRC活性后能减少促炎细胞因子的释放, 从而改善炎症反应[35]。TP53是一种抑癌基因, 有研究发现部分TP53基因位点突变与IBD发病的高风险相关联, 并且TP53突变可以作为IBD患者发生肿瘤的生物标记物[36, 37]。EGFR是一种表皮生长因子受体, 其在85%的非小细胞肺癌细胞中都存在过表达并且与预后不良相关[38]。HSP90AA1属于HSP90家族, 是一种重要的热休克蛋白, 化学物质、热、缺氧等炎症应激会促进HSP90的上调[39, 40], 有研究表明HSP90能抑制胞质中抗炎细胞因子的转录[41]。上述文献提示, 这些靶蛋白可能是砂仁活性成分抗UC的关键靶点。
KEGG通路富集分析结果表明, 鞘磷脂信号通路和趋化因子信号通路可能是中药砂仁抗UC的主要调节通路, 在鞘磷脂信号通路中, 鞘氨醇-1-磷脂(sphingosine 1 phospholipid, S1P) 可通过与免疫细胞表面的S1PR结合, 诱导淋巴细胞归巢, 从而减少淋巴细胞到达炎症损害位置[42]。目前, S1PR受体激动剂奥扎莫得(ozanimod) 已用于人类UC的治疗, 它对S1PR1、S1PR4和S1PR5均有激动作用[43]。因此, 鞘磷脂信号通路可能是砂仁抗UC的分子机制之一。趋化因子信号通路中的JAK/STAT信号通路在砂仁抗UC过程中也发挥重要作用, JAK/STAT信号通路与促炎细胞因子信号转导密切相关, 参与机体细胞的增殖、分化、凋亡及免疫调节等许多重要的生物学过程。通路中的JAKs是一类非受体型酪氨酸激酶, 包括JAK1、JAK2、JAK3和TYK2是许多下游炎性细胞因子必需的信号转导介质, 因此靶向JAKs的小分子抑制剂能够通过影响下游炎性因子的信号转导而发挥抗炎和免疫调节作用[44]。JAK1和JAK3的小分子抑制剂托法替布被FDA批准用于治疗UC, 证明了该靶点的可靠性, 本文通过分子对接证明砂仁的多种活性成分与JAKs具有较强的结合稳定性, Western blot结果证明砂仁提取物能够抑制UC小鼠结肠组织中JAK1的表达和STAT3的磷酸化过程, 所以砂仁可能通过JAK/STAT信号通路产生抗UC作用。
综上所述, 本文通过网络药理学和实验验证相结合的方法对中药砂仁的抗UC作用的药理机制进行探究, 结果表明, 砂仁活性成分抗UC机制可能涉及鞘磷脂通路和JAK/STAT信号通路等途径。通过分子对接和Western blot实验, 本文进一步验证了砂仁潜在活性成分与JAK/STAT通路的相互作用。值得注意的是, 针对目前文献中鲜有报道的砂仁与鞘磷脂通路相互作用, 以及砂仁中活性成分对S1PR受体家族的影响, 还需要相关药理实验结果进一步验证。
作者贡献: 柴常伟负责网络药理学分析和实验验证; 张海婧和吴练秋负责论文审阅指导及研究经费支持。
利益冲突: 所有作者均声明不存在任何利益冲突。
基金
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  • 中国医学科学院医学与健康科技创新工程国家医学科技健康战略平台与体系建设专项(2022-I2M-2-002)
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[1]
Feuerstein JD, Moss AC, Farraye FA. Ulcerative colitis[J]. Mayo Clin Proc, 2019, 94: 1357-1373.
[2]
Gajendran M, Loganathan P, Jimenez G, et al. A comprehensive review and update on ulcerative colitis[J]. Dis Mon, 2019, 65: 100851.
[3]
Jeong DY, Kim S, Son MJ, et al. Induction and maintenance treatment of inflammatory bowel disease: a comprehensive review[J]. Autoimmun Rev, 2019, 18: 439-454.
[4]
Alimohammadi N, Koosha F, Rafeian-Kopaei M. Current, new and future therapeutic targets in inflammatory bowel disease: a systematic review[J]. Curr Pharm Des, 2020, 26: 2668-2675.
[5]
Bertani L, Rossari F, Barberio B, et al. Novel prognostic biomarkers of mucosal healing in ulcerative colitis patients treated with anti-TNF: neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio[J]. Inflamm Bowel Dis, 2020, 26: 1579-1587.
[6]
Chen HT, Huang HL, Xu HM, et al. Fecal microbiota transplantation ameliorates active ulcerative colitis[J]. Exp Ther Med, 2020, 19: 2650-2660.
[7]
Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies[J]. Lancet, 2017, 390: 2769-2778.
[8]
Kaplan GG. The global burden of IBD: from 2015 to 2025[J]. Nat Rev Gastroenterol Hepatol, 2015, 12: 720-727.
[9]
Burri E, Maillard MH, Schoepfer AM, et al. Treatment algorithm for mild and moderate-to-severe ulcerative colitis: an update[J]. Digestion, 2020, 101Suppl 1: 2-15.
[10]
Grootjans J, Krupka N, Hosomi S, et al. Epithelial endoplasmic reticulum stress orchestrates a protective IgA response[J]. Science, 2019, 363: 993-998.
[11]
Li G. Traditional Chinese medicine treatment of gastric ulcer, chronic colitis in some cases[J]. J Changchun Univ Chin Med (长春中医药大学学报), 2009, 25: 869.
[12]
Ma D, Wang X. Experience of treating ulcerative colitis with traditional Chinese medicine[J]. Med Inform (医学信息), 2010, 5: 409-410.
[13]
Pai R, Ohta M, Itani RM, et al. Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats[J]. Gastroenterology, 1998, 114: 706-713.
[14]
Jafri MA, Farah, Javed K, et al. Evaluation of the gastric antiulcerogenic effect of large cardamom (fruits of Amomum subulatum Roxb)[J]. J Ethnopharmacol, 2001, 75: 89-94.
[15]
Zhao J, Lv GP, Chen YW, et al. Advanced development in analysis of phytochemicals from medicine and food dual purposes plants used in China[J]. J Chromatogr A, 2011, 1218: 7453-7475.
[16]
Chien MY, Lin YT, Peng FC, et al. Gastroprotective potential against indomethacin and safety assessment of the homology of medicine and food formula cuttlebone complex[J]. Food Funct, 2015, 6: 2803-2812.
[17]
Manning DC, Snyder SH, Kachur JF, et al. Bradykinin receptor-mediated chloride secretion in intestinal function[J]. Nature, 1982, 299: 256-259.
[18]
Tsurumi K, Fujimura H. Effect of anti-inflammatory drugs on endotoxin-induced diarrhea in mice[J]. Jpn J Pharmacol, 1983, 33: 165-173.
[19]
Lee YG, Park JH, Jeon ES, et al. Fructus Amomi Cardamomi extract inhibit coxsackievirus-B3 induced myocarditis in murine myocarditis model[J]. J Microbiol Biotechnol, 2016, 26: 2012-2018.
[20]
Fan Y, Nguyen TV, Piao CH, et al. Fructus Amomi extract attenuates nasal inflammation by restoring Th1/Th2 balance and down-regulation of NF-κB phosphorylation in OVA-induced allergic rhinitis[J]. Biosci Rep, 2022, 42: BSR20212681.
[21]
Zhang T, Lu SH, Bi Q, et al. Volatile oil from Amomi Fructus attenuates 5-fluorouracil-induced intestinal mucositis[J]. Front Pharmacol, 2017, 8: 786.
[22]
Kim SJ, Kim MC, Um JY, et al. The beneficial effect of vanillic acid on ulcerative colitis[J]. Molecules, 2010, 15: 7208-7217.
[23]
Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Res, 2019, 47: W357-W364.
[24]
Gfeller D, Michielin O, Zoete V. Shaping the interaction landscape of bioactive molecules[J]. Bioinformatics, 2013, 29: 3073-3079.
[25]
Fishilevich S, Nudel R, Rappaport N, et al. GeneHancer: genome-wide integration of enhancers and target genes in GeneCards[J]. Database (Oxford), 2017, 2017: bax028.
[26]
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13: 2498-2504.
[27]
Jain AN. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine[J]. J Med Chem, 2003, 46: 499-511.
[28]
Malathi K, Ramaiah S. Molecular docking and molecular dynamics studies to identify potential OXA-10 extended spectrum β-lactamase non-hydrolysing inhibitors for Pseudomonas aeruginosa[J]. Cell Biochem Biophys, 2016, 74: 141-155.
[29]
Mosli MH, Rivera-Nieves J, Feagan BG. T-cell trafficking and anti-adhesion strategies in inflammatory bowel disease: current and future prospects[J]. Drugs, 2014, 74: 297-311.
[30]
Chai C, Zhang Y, Zhang H, et al. Emerging targets and drugs of inflammatory bowel disease[J]. Acta Pharm Sin (药学学报), 2022, 57: 1282-1288.
[31]
Coskun M, Salem M, Pedersen J, et al. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease[J]. Pharmacol Res, 2013, 76: 1-8.
[32]
Zundler S, Neurath MF. Integrating immunologic signaling networks: the JAK/STAT pathway in colitis and colitis-associated cancer[J]. Vaccines (Basel), 2016, 4: 5.
[33]
Verstockt B, Ferrante M, Vermeire S, et al. New treatment options for inflammatory bowel diseases[J]. J Gastroenterol, 2018, 53: 585-590.
[34]
Zhao Y, Luan H, Jiang H, et al. Gegen Qinlian decoction relieved DSS-induced ulcerative colitis in mice by modulating Th17/Treg cell homeostasis via suppressing IL-6/JAK2/STAT3 signaling[J]. Phytomedicine, 2021, 84: 153519.
[35]
Xiu MX, Liu YM, Chen GY, et al. Identifying hub genes, key pathways and immune cell infiltration characteristics in pediatric and adult ulcerative colitis by integrated bioinformatic analysis[J]. Dig Dis Sci, 2021, 66: 3002-3014.
[36]
Du L, Kim JJ, Shen J, et al. KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis[J]. Oncotarget, 2017, 8: 22175-22186.
[37]
Volodko N, Salla M, Eksteen B, et al. TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development[J]. World J Gastroenterol, 2015, 21: 10358-10366.
[38]
Wei M, Li H, Li Q, et al. Based on network pharmacology to explore the molecular targets and mechanisms of Gegen Qinlian Decoction for the treatment of ulcerative colitis[J]. Biomed Res Int, 2020, 2020: 5217405.
[39]
Joly AL, Deepti A, Seignez A, et al. The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development[J]. Oncogene, 2016, 35: 2842-2851.
[40]
Lin TY, Guo W, Long Q, et al. HSP90 inhibitor encapsulated photo-theranostic nanoparticles for synergistic combination cancer therapy[J]. Theranostics, 2016, 6: 1324-1335.
[41]
Collins CB, Strassheim D, Aherne CM, et al. Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-α and ameliorates murine intestinal inflammation[J]. Inflamm Bowel Dis, 2014, 20: 685-694.
[42]
Gonzalez-Cabrera PJ, Brown S, Studer SM, et al. S1P signaling: new therapies and opportunities[J]. F1000Prime Rep, 2014, 6: 109.
[43]
Degagné E, Saba JD. S1pping fire: sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer[J]. Clin Exp Gastroenterol, 2014, 7: 205-214.
[44]
Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases[J]. J Med Chem, 2014, 57: 5023-5038.
2022年第57卷第11期
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doi: 10.16438/j.0513-4870.2022-0897
  • 接收时间：2022-07-21
  • 首发时间：2025-12-24
  • 出版时间：2022-11-12
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  • 收稿日期：2022-07-21
  • 修回日期：2022-09-13
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中国医学科学院医学与健康科技创新工程国家医学科技健康战略平台与体系建设专项(2022-I2M-2-002)
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    中国医学科学院、北京协和医学院药物研究所, 北京 100050

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*张海婧, E-mail: ;
吴练秋, Tel: 86-10-63031589, Fax: 86-10-63035779, E-mail:
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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