{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T23:02:28Z","timestamp":1775775748932,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>(-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study was to integrate metabolomics and network pharmacology to reveal the mechanism of EGCG in the prevention of obesity-related precocious puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A high-performance liquid chromatography-electrospray ionization ion-trap tandem mass spectrometry (LC-ESI-MS\/MS) was used to analyze the impact of EGCG on serum metabolomics and associated metabolic pathways in a randomized controlled trial. Twelve weeks of EGCG capsules were given to obese girls in this trail. Additionally, the targets and pathways of EGCG in preventing obesity-related precocious puberty network pharmacology were predicted using network pharmacology. Finally, the mechanism of EGCG prevention of obesity-related precocious puberty was elucidated through integrated metabolomics and network pharmacology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum metabolomics screened 234 endogenous differential metabolites, and network pharmacology identified a total of 153 common targets. These metabolites and targets mainly enrichment pathways involving endocrine-related pathways (estrogen signaling pathway, insulin resistance, and insulin secretion), and signal transduction (PI3K-Akt, MAPK, and Jak-STAT signaling pathways). The integrated metabolomics and network pharmacology indicated that AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 may be key targets for EGCG in preventing obesity-related precocious puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>EGCG may contribute to preventing obesity-related precocious puberty through targets such as AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 and multiple signaling pathways, including the estrogen, PI3K-Akt, MAPK, and Jak-STAT pathways. This study provided a theoretical foundation for future research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1159657","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T14:25:42Z","timestamp":1685715942000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["The therapeutic role and potential mechanism of EGCG in obesity-related precocious puberty as determined by integrated metabolomics and network pharmacology"],"prefix":"10.3389","volume":"14","author":[{"given":"Qiuyun","family":"Gu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuju","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieyi","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingwei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuhua","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"l6597","DOI":"10.1136\/bmj.l6597","article-title":"Precocious puberty","volume":"368","author":"Bradley","year":"2020","journal-title":"BMJ"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4158\/EP-2019-0008","article-title":"comparative efficacy and safety of three current clinical treatments for girls with central precocious puberty: a network meta-analysis","volume":"25","author":"Gu","year":"2019","journal-title":"Endocr Pract"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/apa.15554","article-title":"Higher poultry consumption was associated with an earlier age at menarche","volume":"110","author":"Wu","year":"2021","journal-title":"Acta Paediatr"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-015-0130-8","article-title":"Central precocious puberty: update on diagnosis and treatment","volume":"17","author":"Chen","year":"2015","journal-title":"Paediatr Drugs"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.23750\/abm.v90i3.8736","article-title":"Long-term effects and significant adverse drug reactions (ADRs) associated with the use of gonadotropin-releasing hormone analogs (GnRHa) for central precocious puberty: a brief review of literature","volume":"90","author":"De Sanctis","year":"2019","journal-title":"Acta BioMed"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2019.05.011","article-title":"Update on precocious puberty in girls","volume":"32","author":"Eugster","year":"2019","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-20-0103","article-title":"GENETICS IN ENDOCRINOLOGY: genetic etiologies of central precocious puberty and the role of imprinted genes","volume":"183","author":"Roberts","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.001","article-title":"Central ceramide signaling mediates obesity-induced precocious puberty","volume":"32","author":"Heras","year":"2020","journal-title":"Cell Metab"},{"key":"B9","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3390\/children7110220","article-title":"Association between dietary habits and parental health with obesity among children with precocious puberty","volume":"7","author":"Hong","year":"2020","journal-title":"Children (Basel)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000001035","article-title":"The link between obesity and puberty: what is new","volume":"33","author":"Huang","year":"2021","journal-title":"Curr Opin Pediatr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.3390\/ijms21051744","article-title":"Beneficial properties of green tea catechins","volume":"21","author":"Musial","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3390\/ijms20030532","article-title":"Epigallocatechin gallate modulates muscle homeostasis in type 2 diabetes and obesity by targeting energetic and redox pathways: a narrative review","volume":"20","author":"Casanova","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2015.05.003","article-title":"Therapeutic effect of high-dose green tea extract on weight reduction: a randomized, double-blind, placebo-controlled clinical trial","volume":"35","author":"Chen","year":"2016","journal-title":"Clin Nutr"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.736724","article-title":"Effect of decaffeinated green tea polyphenols on body fat and precocious puberty in obese girls: a randomized controlled trial","volume":"12","author":"Xie","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/jcsm.12246","article-title":"Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia","volume":"9","author":"Yang","year":"2018","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.11.004","article-title":"Network pharmacology: curing causal mechanisms instead of treating symptoms","volume":"43","author":"Nogales","year":"2022","journal-title":"Trends Pharmacol Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"111405","DOI":"10.1016\/j.foodres.2022.111405","article-title":"Acrylamide induced glucose metabolism disorder in rats involves gut microbiota dysbiosis and changed bile acids metabolism","volume":"157","author":"Yue","year":"2022","journal-title":"Food Res Int"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv951","article-title":"PubChem substance and compound databases","volume":"44","author":"Kim","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal protein knowledgebase in 2021","volume":"49","author":"Consortium","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards suite: from gene data mining to disease genome sequence analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr Protoc Bioinf"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1021","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Pi\u00f1ero","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa891","article-title":"Comparative toxicogenomics database (CTD): update 2021","volume":"49","author":"Davis","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an r package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1004","article-title":"RCSB protein data bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy","volume":"47","author":"Burley","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00380-0","article-title":"Causes, diagnosis, and treatment of central precocious puberty","volume":"4","author":"Latronico","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B29","article-title":"Disorders of puberty: an approach to diagnosis and management","volume":"96","author":"Klein","year":"2017","journal-title":"Am Fam Physician"},{"key":"B30","doi-asserted-by":"publisher","first-page":"109085","DOI":"10.1016\/j.jnutbio.2022.109085","article-title":"Green tea catechin EGCG could prevent obesity-related precocious puberty through NKB\/NK3R signaling pathway","volume":"108","author":"Gu","year":"2022","journal-title":"J\u00a0Nutr Biochem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2018.05.008","article-title":"Central precocious puberty: from genetics to treatment","volume":"32","author":"Aguirre","year":"2018","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB signaling: navigating the network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.yexcr.2014.09.011","article-title":"Involvement of IGF-1 and MEOX2 in PI3K\/Akt1\/2 and ERK1\/2 pathways mediated proliferation and differentiation of perivascular adipocytes","volume":"331","author":"Liu","year":"2015","journal-title":"Exp Cell Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"110934","DOI":"10.1016\/j.mce.2020.110934","article-title":"Are glyphosate and glyphosate-based herbicides endocrine disruptors that alter female fertility","volume":"518","author":"Ingaramo","year":"2020","journal-title":"Mol Cell Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2019.06.017","article-title":"The interference of DEHP in precocious puberty of females mediated by the hypothalamic IGF-1\/PI3K\/Akt\/mTOR signaling pathway","volume":"181","author":"Shao","year":"2019","journal-title":"Ecotoxicol Environ Saf"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2015.1031102","article-title":"Association of estrogen receptor gene polymorphisms with human precocious puberty: a systematic review and meta-analysis","volume":"31","author":"Luo","year":"2015","journal-title":"Gynecol Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010716-104651","article-title":"GPER (GPR30): a nongenomic receptor (GPCR) for steroid hormones with implications for cardiovascular disease and cancer","volume":"57","author":"Feldman","year":"2017","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2018.4467","article-title":"Kempisty, genes involved in the processes of cell proliferation, migration, adhesion, and tissue development as new potential markers of porcine granulosa cellular processes : a microarray approach","volume":"38","author":"O\u017cegowska","year":"2019","journal-title":"DNA Cell Biol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.630504","article-title":"Melatonin: multi-target mechanism against diminished ovarian reserve based on network pharmacology","volume":"12","author":"Yang","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2974-10.2011","article-title":"Jak2 is necessary for neuroendocrine control of female reproduction","volume":"31","author":"Wu","year":"2011","journal-title":"J Neurosci"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1159657\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T14:25:47Z","timestamp":1685715947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1159657\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,2]]},"references-count":40,"alternative-id":["10.3389\/fendo.2023.1159657"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1159657","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,2]]},"article-number":"1159657"}}