{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:49:45Z","timestamp":1784126985265,"version":"3.55.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803024"],"award-info":[{"award-number":["81803024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["DUT21LK23"],"award-info":[{"award-number":["DUT21LK23"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013804","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1016\/j.ejphar.2021.174680","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T02:36:32Z","timestamp":1638930992000},"page":"174680","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Berberine inhibits pancreatic intraepithelial neoplasia by inhibiting glycolysis via the adenosine monophosphate -activated protein kinase pathway"],"prefix":"10.1016","volume":"915","author":[{"given":"Mengmeng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3383-5587","authenticated-orcid":false,"given":"Yue","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.174680_bib1","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1097\/MPA.0000000000000913","article-title":"Paracrine secretion of TGF-\u03b2 by ductal cells promotes acinar-to-ductal metaplasia in cultured human exocrine pancreas tissues","volume":"46","author":"Akanuma","year":"2017","journal-title":"Pancreas"},{"key":"10.1016\/j.ejphar.2021.174680_bib2","doi-asserted-by":"crossref","first-page":"7945","DOI":"10.3748\/wjg.v23.i45.7945","article-title":"Pancreatic acinar cell carcinoma: a review on molecular profiling of patient tumors","volume":"23","author":"Al-Hader","year":"2017","journal-title":"World J. Gastroenterol.: WJG"},{"key":"10.1016\/j.ejphar.2021.174680_bib3","doi-asserted-by":"crossref","first-page":"107372","DOI":"10.1016\/j.intimp.2021.107372","article-title":"Fraxetin prevented sodium fluoride-induced chronic pancreatitis in rats: role of anti-inflammatory, antioxidant, antifibrotic and anti-apoptotic activities","volume":"93","author":"Balaha","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejphar.2021.174680_bib4","doi-asserted-by":"crossref","first-page":"115162","DOI":"10.1016\/j.taap.2020.115162","article-title":"Berberine attenuates severity of chronic pancreatitis and fibrosis via AMPK-mediated inhibition of TGF-\u03b21\/Smad signaling and M2 polarization","volume":"403","author":"Bansod","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174680_bib5","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.jep.2013.07.025","article-title":"Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells","volume":"149","author":"Cao","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.ejphar.2021.174680_bib6","doi-asserted-by":"crossref","first-page":"1250684","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1\u03b1-mediated aerobic glycolysis as metabolic basis for trained immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2021.174680_bib7","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1080\/15548627.2016.1192753","article-title":"Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling","volume":"12","author":"Choi","year":"2016","journal-title":"Autophagy"},{"key":"10.1016\/j.ejphar.2021.174680_bib8","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jcmgh.2020.10.008","article-title":"Deficient endoplasmic reticulum acetyl-CoA import in pancreatic acinar cells leads to chronic pancreatitis","volume":"11","author":"Cooley","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"10.1016\/j.ejphar.2021.174680_bib9","doi-asserted-by":"crossref","DOI":"10.3390\/molecules24010103","article-title":"Preparation and evaluation of antidiabetic agents of berberine organic acid salts for enhancing the bioavailability","volume":"24","author":"Cui","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.ejphar.2021.174680_bib10","doi-asserted-by":"crossref","first-page":"6188","DOI":"10.1158\/1078-0432.CCR-12-1789","article-title":"Overexpression of ecdysoneless in pancreatic cancer and its role in oncogenesis by regulating glycolysis","volume":"18","author":"Dey","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejphar.2021.174680_bib11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jbior.2019.02.001","article-title":"Pancreatic cancer tumorspheres are cancer stem-like cells with increased chemoresistance and reduced metabolic potential","volume":"72","author":"Domenichini","year":"2019","journal-title":"Adv. Biol. Regul."},{"key":"10.1016\/j.ejphar.2021.174680_bib12","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1126\/science.1196371","article-title":"Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy","volume":"331","author":"Egan","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2021.174680_bib13","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cmet.2012.12.001","article-title":"AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo","volume":"17","author":"Faubert","year":"2013","journal-title":"Cell. Metab."},{"key":"10.1016\/j.ejphar.2021.174680_bib14","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. Cell"},{"key":"10.1016\/j.ejphar.2021.174680_bib15","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3389\/fphys.2014.00426","article-title":"Diabetes, pancreatic cancer, and metformin therapy","volume":"5","author":"Gong","year":"2014","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ejphar.2021.174680_bib16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1053\/j.gastro.2015.01.012","article-title":"Impaired autophagy triggers chronic pancreatitis: lessons from pancreas-specific atg5 knockout mice","volume":"148","author":"Gukovsky","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejphar.2021.174680_bib17","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.tcb.2015.10.013","article-title":"AMPK: an energy-sensing pathway with multiple inputs and outputs","volume":"26","author":"Hardie","year":"2015","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.ejphar.2021.174680_bib18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12957-020-01884-x","article-title":"Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1\u03b1\/mTOR-mediated autophagy","volume":"18","author":"Hong","year":"2020","journal-title":"World J. Surg. Oncol."},{"key":"10.1016\/j.ejphar.2021.174680_bib19","doi-asserted-by":"crossref","first-page":"10861","DOI":"10.18632\/aging.102489","article-title":"Glycolysis gene expression profilings screen for prognostic risk signature of hepatocellular carcinoma","volume":"11","author":"Jiang","year":"2019","journal-title":"Aging"},{"key":"10.1016\/j.ejphar.2021.174680_bib20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1053\/j.gastro.2017.03.008","article-title":"Increased serotonin signaling contributes to the Warburg effect in pancreatic tumor cells under metabolic stress and promotes growth of pancreatic tumors in mice","volume":"153","author":"Jiang","year":"2017","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejphar.2021.174680_bib21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1080\/15548627.2017.1381804","article-title":"Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of HK2 (hexokinase 2)","volume":"14","author":"Jiao","year":"2018","journal-title":"Autophagy"},{"key":"10.1016\/j.ejphar.2021.174680_bib22","first-page":"3825","article-title":"Cell metabolomics reveals berberine-inhibited pancreatic cancer cell viability and metastasis by regulating citrate metabolism","author":"Jingjing Liu","year":"2020","journal-title":"J. Proteome Res."},{"key":"10.1016\/j.ejphar.2021.174680_bib23","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/cbin.10915","article-title":"Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism","volume":"42","author":"Ke","year":"2018","journal-title":"Cell Biol. Int."},{"key":"10.1016\/j.ejphar.2021.174680_bib24","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1038\/emm.2016.16","article-title":"AMPK activators: mechanisms of action and physiological activities","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.ejphar.2021.174680_bib25","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1128\/MCB.00244-16","article-title":"AMPK phosphorylates desnutrin\/ATGL and hormone-sensitive lipase to regulate lipolysis and fatty acid oxidation within adipose tissue","volume":"36","author":"Kim","year":"2016","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.ejphar.2021.174680_bib26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/03602532.2017.1306544","article-title":"The metabolism of berberine and its contribution to the pharmacological effects","author":"Kun Wang","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"10.1016\/j.ejphar.2021.174680_bib27","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1038\/labinvest.2017.71","article-title":"Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory responses and the consequent EGFR signaling-involved tumor cell growth","volume":"97","author":"Li","year":"2017","journal-title":"Lab. Invest."},{"key":"10.1016\/j.ejphar.2021.174680_bib28","doi-asserted-by":"crossref","first-page":"6200","DOI":"10.1038\/ncomms7200","article-title":"Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia","volume":"6","author":"Liou","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejphar.2021.174680_bib29","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1021\/acs.jproteome.0c00394","article-title":"Cell metabolomics reveals berberine-inhibited pancreatic cancer cell viability and metastasis by regulating citrate metabolism","volume":"19","author":"Liu","year":"2020","journal-title":"J. Proteome Res."},{"key":"10.1016\/j.ejphar.2021.174680_bib30","doi-asserted-by":"crossref","first-page":"113776","DOI":"10.1016\/j.bcp.2019.113776","article-title":"Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP\/SREBP-1 signaling pathway-mediated lipogenesis","volume":"174","author":"Liu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174680_bib31","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.3390\/ijms19103092","article-title":"Nutritional modulation of AMPK-impact upon metabolic-inflammation","volume":"19","author":"Lyons","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejphar.2021.174680_bib32","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.4161\/auto.20586","article-title":"AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization","volume":"8","author":"Mack","year":"2012","journal-title":"Autophagy"},{"key":"10.1016\/j.ejphar.2021.174680_bib33","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1136\/gutjnl-2019-318362","article-title":"Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia-mesenchymal transition during pancreatic carcinogenesis","volume":"69","author":"Niu","year":"2020","journal-title":"Gut"},{"key":"10.1016\/j.ejphar.2021.174680_bib34","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41586-020-2428-0","article-title":"Intracellular pH controls WNT downstream of glycolysis in amniote embryos","volume":"584","author":"Oginuma","year":"2020","journal-title":"Nature (London)"},{"key":"10.1016\/j.ejphar.2021.174680_bib35","doi-asserted-by":"crossref","first-page":"74768","DOI":"10.18632\/oncotarget.11013","article-title":"Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions","volume":"7","author":"Pinho","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejphar.2021.174680_bib36","first-page":"98","article-title":"Betulinic acid inhibits stemness and EMT of pancreatic cancer cells via activation of AMPK signaling","volume":"54","author":"Sun","year":"2019","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.ejphar.2021.174680_bib37","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2021.174680_bib38","doi-asserted-by":"crossref","first-page":"109999","DOI":"10.1016\/j.biopha.2020.109999","article-title":"Serotonin-RhoA\/ROCK axis promotes acinar-to-ductal metaplasia in caerulein-induced chronic pancreatitis","volume":"125","author":"Tao","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejphar.2021.174680_bib39","first-page":"1","article-title":"Anoxic and secretory vacuolation in the acinar cells of the pancreas","volume":"55","author":"Tapp","year":"1970","journal-title":"Q. J. Exp. Physiol. Cogn. Med. Sci."},{"key":"10.1016\/j.ejphar.2021.174680_bib40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3390\/cancers12010002","article-title":"Metabolic alterations in pancreatic cancer progression","volume":"12","author":"Vernucci","year":"2019","journal-title":"Cancers"},{"key":"10.1016\/j.ejphar.2021.174680_bib41","series-title":"Pancreatic Acinar-to-Ductal Metaplasia and Pancreatic Cancer","first-page":"299","author":"Wang","year":"2018"},{"key":"10.1016\/j.ejphar.2021.174680_bib42","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.metabol.2017.02.003","article-title":"Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism","volume":"70","author":"Wang","year":"2017","journal-title":"Metabolism"},{"key":"10.1016\/j.ejphar.2021.174680_bib43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00018-019-03278-z","article-title":"The enhancement of glycolysis regulates pancreatic cancer metastasis","volume":"77","author":"Yang","year":"2020","journal-title":"Cell. Mol. Life Sci.: CMLS"},{"key":"10.1016\/j.ejphar.2021.174680_bib44","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00018-019-03278-z","article-title":"The enhancement of glycolysis regulates pancreatic cancer metastasis","volume":"77","author":"Yang","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.ejphar.2021.174680_bib45","doi-asserted-by":"crossref","first-page":"6150","DOI":"10.12659\/MSM.907377","article-title":"The effects of berberine on concanavalin a-induced autoimmune hepatitis (AIH) in mice and the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway","author":"Yangyang Wang","year":"2017","journal-title":"Med. Sci. Monit."},{"issue":"11\u201312","key":"10.1016\/j.ejphar.2021.174680_bib46","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/lipd.12200","article-title":"Berberine inhibits adipogenesis in porcine adipocytes via AMP-activated protein kinase-dependent and -independent mechanisms","author":"Yongqing Yang","year":"2019","journal-title":"Lipids"},{"key":"10.1016\/j.ejphar.2021.174680_bib47","doi-asserted-by":"crossref","first-page":"794","DOI":"10.7150\/ijbs.18969","article-title":"Berberine reverses hypoxia-induced chemoresistance in breast cancer through the inhibition of AMPK- HIF-1\u03b1","author":"Yue Pan","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.ejphar.2021.174680_bib48","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.12393","article-title":"Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer","volume":"50","author":"Zhao","year":"2017","journal-title":"Cell Prolif"},{"key":"10.1016\/j.ejphar.2021.174680_bib49","doi-asserted-by":"crossref","first-page":"110821","DOI":"10.1016\/j.biopha.2020.110821","article-title":"Sodium-glucose co-transporter-2 (SGLT-2) inhibition reduces glucose uptake to induce breast cancer cell growth arrest through AMPK\/mTOR pathway","volume":"132","author":"Zhou","year":"2020","journal-title":"Biomed. Pharmacother."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921008360?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921008360?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:55:42Z","timestamp":1757976942000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921008360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":49,"alternative-id":["S0014299921008360"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174680","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Berberine inhibits pancreatic intraepithelial neoplasia by inhibiting glycolysis via the adenosine monophosphate -activated protein kinase pathway","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174680","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":"174680"}}