{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:53:57Z","timestamp":1790823237782,"version":"4.1.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.jep.2021.114119","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T14:58:34Z","timestamp":1618930714000},"page":"114119","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"special_numbering":"C","title":["The mechanisms of action of WeiChang'An Pill (WCAP) treat diarrhoea-predominant irritable bowel syndrome (IBS-D) using network pharmacology approach and in vivo studies"],"prefix":"10.1016","volume":"275","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-8817","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhao","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-2070","authenticated-orcid":false,"given":"Jie","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqi","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5219-0817","authenticated-orcid":false,"given":"Nadia","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9858-4451","authenticated-orcid":false,"given":"Haocheng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2021.114119_bib1","doi-asserted-by":"crossref","first-page":"109427","DOI":"10.1016\/j.biopha.2019.109427","article-title":"Protective effects of Weipixiao decoction against MNNG-induced gastric precancerous lesions in rats","volume":"120","author":"Cai","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2021.114119_bib2","first-page":"4117","article-title":"Aquaporins 1, 3 and 8 expression and cytokines in irritable bowel syndrome rats' colon via cAMP-PKA pathway","volume":"11","author":"Chao","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"10.1016\/j.jep.2021.114119_bib3","doi-asserted-by":"crossref","first-page":"24245","DOI":"10.1038\/srep24245","article-title":"Drug target identification using network analysis: taking active components in Sini decoction as an example","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2021.114119_bib4","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.1039\/C4MB00048J","article-title":"Investigation of the therapeutic effectiveness of active components in Sini decoction by a comprehensive GC\/LC-MS based metabolomics and network pharmacology approaches","volume":"10","author":"Chen","year":"2014","journal-title":"Mol. Biosyst."},{"key":"10.1016\/j.jep.2021.114119_bib5","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1056\/NEJMra1607547","article-title":"Irritable bowel syndrome","volume":"376","author":"Ford","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.jep.2021.114119_bib6","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.3109\/13880209.2013.879601","article-title":"Gastrointestinal effect of methanol extract of Radix Aucklandiae and selected active substances on the transit activity of rat isolated intestinal strips","volume":"52","author":"Guo","year":"2014","journal-title":"Pharm. Biol."},{"key":"10.1016\/j.jep.2021.114119_bib7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S2468-1253(16)30023-1","article-title":"Pathophysiology of irritable bowel syndrome","volume":"1","author":"Holtmann","year":"2016","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"10.1016\/j.jep.2021.114119_bib8","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/bib\/bbt035","article-title":"Systems pharmacology in drug discovery and therapeutic insight for herbal medicines","volume":"15","author":"Huang","year":"2014","journal-title":"Briefings Bioinf."},{"key":"10.1016\/j.jep.2021.114119_bib9","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0254-6272(12)60031-4","article-title":"Effects of Wei Chang an pill on enzyme activity and levels of vasoactive peptide and substance P in the small intestine of rats with compound diarrhea","volume":"32","author":"Hu","year":"2012","journal-title":"J. Tradit. Chin. Med."},{"key":"10.1016\/j.jep.2021.114119_bib10","first-page":"2899","article-title":"Effect of Weichang'an pill on intestinal digestive ferment and the AQP4 concentration in proximal colon in IBS-D rats","volume":"35","author":"Hu","year":"2010","journal-title":"China J. Chin. Mater. Med."},{"key":"10.1016\/j.jep.2021.114119_bib11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.foodchem.2017.01.074","article-title":"Isolation, structures and bioactivities of the polysaccharides from jujube fruit (Ziziphus jujuba Mill.): a review","volume":"227","author":"Ji","year":"2017","journal-title":"Food Chem."},{"key":"10.1016\/j.jep.2021.114119_bib12","doi-asserted-by":"crossref","first-page":"109442","DOI":"10.1016\/j.biopha.2019.109442","article-title":"Xiaoerfupi alleviates the symptoms of functional dyspepsia by regulating the HTR3A and c-FOS","volume":"120","author":"Ji","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2021.114119_bib13","doi-asserted-by":"crossref","first-page":"S110","DOI":"10.1038\/533S110a","article-title":"Diagnostics: filling in the missing pieces","volume":"533","author":"Katsnelson","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.jep.2021.114119_bib14","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","article-title":"Bowel disorders","volume":"150","author":"Lacy","year":"2016","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jep.2021.114119_bib15","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3109\/00365529709011203","article-title":"Stool form scale as a useful guide to intestinal transit time","volume":"32","author":"Lewis","year":"1997","journal-title":"Scand. J. Gastroenterol."},{"key":"10.1016\/j.jep.2021.114119_bib16","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1166\/jctn.2017.6491","article-title":"A network motif extension-based method for identifying essential proteins from protein\u2013protein interaction networks","volume":"14","author":"Li","year":"2017","journal-title":"J. Comput. Theor. Nanosci."},{"key":"10.1016\/j.jep.2021.114119_bib17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.compbiolchem.2011.04.002","article-title":"A local average connectivity-based method for identifying essential proteins from the network level","volume":"35","author":"Li","year":"2011","journal-title":"Comput. Biol. Chem."},{"key":"10.1016\/j.jep.2021.114119_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005527","article-title":"Bacillus bombysepticus alpha-toxin binding to G protein-coupled receptor kinase 2 regulates cAMP\/PKA signaling pathway to induce host death","volume":"12","author":"Lin","year":"2016","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.jep.2021.114119_bib19","first-page":"77","article-title":"Clinical curative effect of Trimebutine Maleate combined with Weichang'an pill in the treatment of irritable bowel syndrome","volume":"23","author":"Li","year":"2017","journal-title":"Contemp. Med."},{"issue":"560\u2013565","key":"10.1016\/j.jep.2021.114119_bib20","article-title":"Serotonin transporter gene promoter region polymorphisms and serotonin transporter expression in the colonic mucosa of irritable bowel syndrome patients","volume":"24","author":"Liang","year":"2012","journal-title":"Neuro Gastroenterol. Motil."},{"key":"10.1016\/j.jep.2021.114119_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0168703","article-title":"Influence of polymorphisms in the HTR3A and HTR3B genes on experimental pain and the effect of the 5-HT3 antagonist granisetron","volume":"11","author":"Louca Jounger","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2021.114119_bib22","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrgastro.2013.105","article-title":"Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets","volume":"10","author":"Mawe","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.jep.2021.114119_bib23","series-title":"Pharmacopoeia of People's Republic of China","year":"2015"},{"key":"10.1016\/j.jep.2021.114119_bib24","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2217\/14622416.9.5.501","article-title":"Serotonin type 3 receptor genes: HTR3A, B, C, D, E","volume":"9","author":"Niesler","year":"2008","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.jep.2021.114119_bib25","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1006\/bbrc.1995.2571","article-title":"Hyperphosphorylation of the cytoskeletal protein Tau by the MAP-kinase PK40erk2: regulation by prior phosphorylation with cAMP-dependent protein kinase A","volume":"215","author":"Raghunandan","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jep.2021.114119_bib26","first-page":"147648","article-title":"Protein-protein interaction detection: methods and analysis","author":"Rao","year":"2014","journal-title":"Int. J. Proteomics."},{"key":"10.1016\/j.jep.2021.114119_bib27","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.bbi.2018.05.024","article-title":"Early life stress in mice is a suitable model for Irritable Bowel Syndrome but does not predispose to colitis nor increase susceptibility to enteric infections","volume":"73","author":"Riba","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.jep.2021.114119_bib28","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.3389\/fphar.2019.01600","article-title":"Rhein suppresses lung inflammatory injury induced by human respiratory syncytial virus through inhibiting NLRP3 inflammasome activation via NF-kappaB pathway in mice","volume":"10","author":"Shen","year":"2019","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2021.114119_bib29","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.biopha.2018.02.047","article-title":"Clarifying of the potential mechanism of Sinisan formula for treatment of chronic hepatitis by systems pharmacology method","volume":"100","author":"Shu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2021.114119_bib30","doi-asserted-by":"crossref","first-page":"8103","DOI":"10.3748\/wjg.v21.i26.8103","article-title":"Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation","volume":"21","author":"Singh","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.jep.2021.114119_bib31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1053\/j.gastro.2020.04.014","article-title":"Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome foundation global study","volume":"160","author":"Sperber","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jep.2021.114119_bib32","first-page":"23","article-title":"Effects of JXZXP on AQP4, PKA and cAMP expression of irritable bowel syndrome rats with damp-heat diarrhea type","volume":"34","author":"Tan","year":"2012","journal-title":"J. Tradit. Chin. Med. Univ. Hunan"},{"key":"10.1016\/j.jep.2021.114119_bib33","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biosystems.2014.11.005","article-title":"CytoNCA: a cytoscape plugin for centrality analysis and evaluation of protein interaction networks","volume":"127","author":"Tang","year":"2015","journal-title":"Biosystems"},{"key":"10.1016\/j.jep.2021.114119_bib34","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/bab.1784","article-title":"Weichang'an suppressed migration and invasion of HCT116 cells by inhibiting Wnt\/beta-catenin pathway while upregulating ARHGAP25","volume":"66","author":"Tao","year":"2019","journal-title":"Biotechnol. Appl. Biochem."},{"key":"10.1016\/j.jep.2021.114119_bib35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/00001574-200203000-00002","article-title":"New advances in the molecular and cellular biology of the small intestine","volume":"18","author":"Walters","year":"2002","journal-title":"Curr. Opin. Gastroenterol."},{"key":"10.1016\/j.jep.2021.114119_bib36","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1053\/j.gastro.2006.11.014","article-title":"The vanilloid receptor initiates and maintains colonic hypersensitivity induced by neonatal colon irritation in rats","volume":"132","author":"Wang","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jep.2021.114119_bib37","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.3390\/ijms13066964","article-title":"A novel chemometric method for the prediction of human oral bioavailability","volume":"13","author":"Xu","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jep.2021.114119_bib38","doi-asserted-by":"crossref","first-page":"R93","DOI":"10.1530\/JME-15-0316","article-title":"Targeting cAMP\/PKA pathway for glycemic control and type 2 diabetes therapy","volume":"57","author":"Yang","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"10.1016\/j.jep.2021.114119_bib39","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fncel.2019.00030","article-title":"Resveratrol improves brain-gut Axis by regulation of 5-HT-dependent signaling in the rat model of irritable bowel syndrome","volume":"13","author":"Yu","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.jep.2021.114119_bib40","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.3748\/wjg.v25.i29.3956","article-title":"Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats","volume":"25","author":"Yu","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.jep.2021.114119_bib41","doi-asserted-by":"crossref","first-page":"S 788","DOI":"10.1016\/S0016-5085(20)32644-5","article-title":"MO1103 effect of weichang'an pill on th17\/treg immune balance in mice with ulcerative colitis","volume":"158","author":"Zhang","year":"2020","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jep.2021.114119_bib42","first-page":"1092","article-title":"Research of different modeling methods of rats with diarrhea-predominant irritable bowel syndrome","volume":"36","author":"Zhang","year":"2018","journal-title":"Chin. Arch. Tradit. Chin. Med."},{"key":"10.1016\/j.jep.2021.114119_bib43","first-page":"511","article-title":"Biopharmaceuticals classification system (BCS) of nuciferin in Nelumbinis Folium","volume":"43","author":"Zhao","year":"2018","journal-title":"Zhongguo Zhongyao Zazhi"},{"key":"10.1016\/j.jep.2021.114119_bib44","doi-asserted-by":"crossref","first-page":"104935","DOI":"10.1016\/j.phrs.2020.104935","article-title":"Artificial intelligence and network pharmacology based investigation of pharmacological mechanism and substance basis of Xiaokewan in treating diabetes","volume":"159","author":"Zhu","year":"2020","journal-title":"Pharmacol. Res."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874121003469?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874121003469?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:04:34Z","timestamp":1759943074000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874121003469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":44,"alternative-id":["S0378874121003469"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2021.114119","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The mechanisms of action of WeiChang'An Pill (WCAP) treat diarrhoea-predominant irritable bowel syndrome (IBS-D) using network pharmacology approach and in vivo studies","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2021.114119","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"114119"}}