{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T18:36:00Z","timestamp":1778956560307,"version":"3.51.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Fund","doi-asserted-by":"publisher","award":["2018M630377"],"award-info":[{"award-number":["2018M630377"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010722","name":"Harbin Medical University Scientific Research Innovation Fund","doi-asserted-by":"publisher","award":["2017JCZX59"],"award-info":[{"award-number":["2017JCZX59"]}],"id":[{"id":"10.13039\/100010722","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":[[2020,11]]},"DOI":"10.1016\/j.jep.2020.113129","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T21:47:20Z","timestamp":1595886440000},"page":"113129","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":36,"special_numbering":"C","title":["Study on the mechanism of Gegen Qinlian Decoction for treating type II diabetes mellitus by integrating network pharmacology and pharmacological evaluation"],"prefix":"10.1016","volume":"262","author":[{"given":"Xinyi","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meilu","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanying","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyou","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2020.113129_bib1","first-page":"5386193","article-title":"A review on sex steroid hormone estrogen receptors in mammals and fish","author":"Amenyogbe","year":"2020","journal-title":"Internet J. Endocrinol."},{"key":"10.1016\/j.jep.2020.113129_bib2","article-title":"Identification of gene networks and pathways associated with Guillain\u2013Barr\u00e9 syndrome","volume":"7","author":"Chang","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2020.113129_bib3","doi-asserted-by":"crossref","DOI":"10.7189\/jogh.04.010404","article-title":"Urbanization and prevalence of type 2 diabetes in southern Asia: a systematic analysis","volume":"4","author":"Cheema","year":"2014","journal-title":"J. Glob. Health"},{"key":"10.1016\/j.jep.2020.113129_bib4","first-page":"649","article-title":"An overview on the therapeutic role of traditional Chinese medicine in the coronary heart disease. J Emerg Syndromes","volume":"19","author":"Cui","year":"2010","journal-title":"J. Tradit. Chin. Med."},{"key":"10.1016\/j.jep.2020.113129_bib5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13293-020-0283-1","article-title":"Neuroprotective and neurotoxic outcomes of androgens and estrogens in an oxidative stress environment","volume":"11","author":"Duong","year":"2020","journal-title":"Biol. Sex Differ."},{"key":"10.1016\/j.jep.2020.113129_bib6","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.biopha.2018.10.026","article-title":"CAPE-pNO2 attenuates diabetic cardiomyopathy through the NOX4\/NF-\u03baB pathway in STZ-induced diabetic mice","volume":"108","author":"Fan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2020.113129_bib7","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.clindermatol.2010.11.009","article-title":"Insulin allergy","volume":"29","author":"Ghazavi","year":"2011","journal-title":"Clin. Dermatol."},{"key":"10.1016\/j.jep.2020.113129_bib8","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: the next paradigm in drug discovery","volume":"4","author":"Hopkins","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jep.2020.113129_bib9","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.jep.2015.11.018","article-title":"Anti-H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis","volume":"176","author":"Ji","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2020.113129_bib10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acs.jnatprod.5b00877","article-title":"Bioactive constituents of Glycyrrhiza uralensis (Licorice): discovery of the effective components of a traditional herbal medicine","volume":"79","author":"Ji","year":"2016","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.jep.2020.113129_bib11","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.7150\/thno.23624","article-title":"Estrogen receptors orchestrate cell growth and differentiation to facilitate liver regeneration","volume":"8","author":"Kao","year":"2018","journal-title":"Theranostics"},{"key":"10.1016\/j.jep.2020.113129_bib12","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1039\/C5NP00005J","article-title":"Network pharmacology Applications to map the unexplored target space and therapeutic potential of natural products","volume":"32","author":"Kibble","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"10.1016\/j.jep.2020.113129_bib13","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3724\/SP.J.1009.2013.00110","article-title":"Traditional Chinese medicine network pharmacology: theory, methodology and application","volume":"11","author":"Li","year":"2013","journal-title":"Chin. J. Nat. Med."},{"key":"10.1016\/j.jep.2020.113129_bib14","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1186\/1471-2105-11-S11-S6","article-title":"Herb network construction and co-module analysis for uncovering the Combination rule of traditional Chinese herbal formulae","volume":"11","author":"Li","year":"2010","journal-title":"BMC Bioinf."},{"key":"10.1016\/j.jep.2020.113129_bib15","first-page":"1415","article-title":"Therapeutic effects of Gegen Qinlian decoction and its mechanism of action on type 2 diabetics rats","volume":"48","author":"Li","year":"2013","journal-title":"Acta Pharmacol. Sin. B"},{"key":"10.1016\/j.jep.2020.113129_bib16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3109\/13685538.2013.772134","article-title":"Estrogen receptor alpha single nucleotide polymorphism as predictor of diabetes type 2 risk in hypogonadal men","volume":"16","author":"Linn\u00e9r","year":"2013","journal-title":"Aging Male"},{"key":"10.1016\/j.jep.2020.113129_bib17","article-title":"Polymorphisms in the ESR1 and ESR2 genes are associated with type 2 diabetes in females of Mexican-American families","volume":"64","author":"Mamtani","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.jep.2020.113129_bib18","doi-asserted-by":"crossref","first-page":"444","DOI":"10.4239\/wjd.v5.i4.444","article-title":"Type 2 diabetes and cardiovascular disease: have all risk factors the same strength?","volume":"5","author":"Mart\u00edn-Tim\u00f3n","year":"2014","journal-title":"World J. Diabetes"},{"key":"10.1016\/j.jep.2020.113129_bib19","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1007\/s13300-017-0291-2","article-title":"Effect of liraglutide on type B insulin resistance syndrome and insulin allergy in type 2 diabetes: a Case Report","volume":"8","author":"Matsumoto","year":"2017","journal-title":"Diabetes Ther."},{"key":"10.1016\/j.jep.2020.113129_bib20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/1752-0509-4-158","article-title":"A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder","volume":"4","author":"McEachin","year":"2010","journal-title":"BMC Syst. Biol."},{"key":"10.1016\/j.jep.2020.113129_bib21","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2174\/1573399814666180119141836","article-title":"The role of oestrogen receptor beta (ER\u03b2) in the aetiology and treatment of type 2 diabetes mellitus","volume":"15","author":"Ofosu","year":"2019","journal-title":"Curr. Diabetes Rev."},{"key":"10.1016\/j.jep.2020.113129_bib22","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jsbmb.2018.06.002","article-title":"Functional distinctions associated with the diversity of sex steroid hormone receptors ESR and AR","volume":"184","author":"Ogino","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"10.1016\/j.jep.2020.113129_bib23","first-page":"318613","article-title":"Modulation of PPAR-\u03b3 nutraceutics as complementary treatment for obesity-related disorders and inflammatory disease","volume":"10","author":"Ortu\u00f1o Sahag\u00fan","year":"2012","journal-title":"PPAR Res."},{"key":"10.1016\/j.jep.2020.113129_bib24","first-page":"721","article-title":"New paradigm for drug discovery based on network pharmacology","volume":"28","author":"Pan","year":"2009","journal-title":"Chin. J. New Drugs Clin. Remedies"},{"key":"10.1016\/j.jep.2020.113129_bib25","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jgr.2016.08.005","article-title":"Effects of ginseng on two main sex steroid hormone receptors: estrogen and androgen receptors","volume":"41","author":"Park","year":"2017","journal-title":"J. Ginseng Res."},{"key":"10.1016\/j.jep.2020.113129_bib26","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.chroma.2016.02.034","article-title":"A chemical profiling solution for Chinese medicine formulas using comprehensive and loop-based multiple heart-cutting two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry","volume":"1438","author":"Qiao","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"10.1016\/j.jep.2020.113129_bib27","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3389\/fphar.2018.00622","article-title":"A 42-markers pharmacokinetic study reveals interactions of berberine and glycyrrhizic acid in the anti-diabetic Chinese medicine formula Gegen-Qinlian decoction","volume":"9","author":"Qiao","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2020.113129_bib28","doi-asserted-by":"crossref","first-page":"39534","DOI":"10.1038\/srep39534","article-title":"Compound to extract to formulation: a knowledge-transmitting approach for metabolites identification of Gegen-qinlian decoction, a traditional Chinese medicine formula","volume":"6","author":"Qiao","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2020.113129_bib29","doi-asserted-by":"crossref","DOI":"10.1152\/ajpregu.00271.2017","article-title":"Insulin sensitivity, leptin, adiponectin, resistin, and testosterone in adult male and female rats after maternal-neonatal separation and environmental stress","volume":"314","author":"Raff","year":"2018","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"10.1016\/j.jep.2020.113129_bib30","first-page":"274","article-title":"Diagnosis and classification of diabetes mellitus","volume":"101","author":"Rossi","year":"2010","journal-title":"Recenti Prog. Med."},{"key":"10.1016\/j.jep.2020.113129_bib31","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ctim.2017.05.004","article-title":"Efficacy and safety of Gegen Qinlian decoction for normalizing hyperglycemia in diabetic patients: a systematic review and meta-analysis of randomized clinical trials","volume":"33","author":"Ryuk","year":"2017","journal-title":"Compl. Ther. Med."},{"key":"10.1016\/j.jep.2020.113129_bib32","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1530\/EJE-17-0124","article-title":"Mechanisms in Endocrinology: the sexually dimorphic role of androgens in human metabolic disease","volume":"177","author":"Schiffer","year":"2017","journal-title":"Eur. J. Endocrinol."},{"key":"10.1016\/j.jep.2020.113129_bib33","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/j.2040-1124.2010.00074.x","article-title":"Report of the committee on the classification and diagnostic criteria of diabetes mellitus","volume":"1","author":"Seino","year":"2010","journal-title":"J. Diabetes Investig."},{"key":"10.1016\/j.jep.2020.113129_bib34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1172\/JCI10583","article-title":"Cellular mechanisms of insulin resistance","volume":"106","author":"Shulman","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jep.2020.113129_bib35","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1021\/np500253m","article-title":"Uralsaponins M-Y, antiviral triterpenoid saponins from the roots of Glycyrrhiza uralensis","volume":"77","author":"Song","year":"2014","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.jep.2020.113129_bib36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0254-6272(11)60013-7","article-title":"Clinical observations on the dose-effect relationship of Gegen Qin Lian decoction on 54 out-patients with Type 2 diabetes","volume":"31","author":"Tong","year":"2011","journal-title":"J. Tradit. Chin. Med."},{"key":"10.1016\/j.jep.2020.113129_bib37","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2147\/CEG.S214196","article-title":"Estradiol accelerates liver regeneration through estrogen receptor alpha","volume":"12","author":"Tsugawa","year":"2019","journal-title":"Clin. Exp. Gastroenterol."},{"key":"10.1016\/j.jep.2020.113129_bib38","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.chroma.2016.05.056","article-title":"Simultaneous quantification of 50 bioactive compounds of the traditional Chinese medicine formula Gegen-Qinlian Decoction using ultra-high performance liquid chromatography coupled with tandem mass spectrometry","volume":"1454","author":"Wang","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"10.1016\/j.jep.2020.113129_bib39","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1111\/j.1463-1326.2012.01601.x","article-title":"PPAR agonists for the treatment of cardiovascular disease in patients with diabetes","volume":"14","author":"Wilding","year":"2012","journal-title":"Diabetes Obes. Metabol."},{"key":"10.1016\/j.jep.2020.113129_bib40","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/ismej.2014.177","article-title":"Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula","volume":"9","author":"Xu","year":"2015","journal-title":"ISME J."},{"key":"10.1016\/j.jep.2020.113129_bib41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13020-018-0208-7","article-title":"Comparing the antidiabetic effects and chemical profiles of raw and fermented Chinese Ge-Gen-Qin-Lian decoction by integrating untargeted metabolomics and targeted analysis","volume":"13","author":"Yan","year":"2018","journal-title":"Chin. Med."},{"key":"10.1016\/j.jep.2020.113129_bib42","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1055\/a-0620-8553","article-title":"Associations of estrogen receptor alpha gene polymorphisms with type 2 diabetes mellitus and metabolic syndrome: a systematic review and meta-analysis","volume":"50","author":"Yang","year":"2018","journal-title":"Horm. Metab. Res."},{"key":"10.1016\/j.jep.2020.113129_bib43","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/iep.12296","article-title":"Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse","volume":"99","author":"Zhang","year":"2018","journal-title":"Int. J. Exp. Pathol."},{"key":"10.1016\/j.jep.2020.113129_bib44","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.2337\/db16-1354","article-title":"Deletion of macrophage mineralocorticoid receptor protects hepatic steatosis and insulin resistance through ER\u03b1\/HGF\/Met pathway","volume":"66","author":"Zhang","year":"2017","journal-title":"Diabetes"},{"key":"10.1016\/j.jep.2020.113129_bib45","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.bbrc.2017.06.118","article-title":"Regulation of testicular steroidogenesis by Foxa3 via transcriptional modulation of ER alpha signaling in type 2 diabetes mellitus (T2DM)","volume":"490","author":"Zhao","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jep.2020.113129_bib46","first-page":"30","article-title":"Clinical observation on 32 cases of Acute bacillary Dysentery Treated by compound Ge gen Qin Lian decoction","volume":"26","author":"Zhu","year":"2006","journal-title":"Henan Tradit. Chin. Med."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874120330105?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874120330105?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:34:59Z","timestamp":1759941299000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874120330105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":46,"alternative-id":["S0378874120330105"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2020.113129","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Study on the mechanism of Gegen Qinlian Decoction for treating type II diabetes mellitus by integrating network pharmacology and pharmacological evaluation","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2020.113129","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113129"}}