{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:25:13Z","timestamp":1792013113665,"version":"4.4.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinics and Research in Hepatology and Gastroenterology"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.clinre.2022.101976","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T21:23:51Z","timestamp":1655155431000},"page":"101976","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Curcumae longae Rhizoma (Jianghuang) extract reverses the 5-Fluoruracil resistance in colorectal cancer cells via TLR4\/PI3K\/Akt\/mTOR pathway"],"prefix":"10.1016","volume":"46","author":[{"given":"Zhongyi","family":"Teng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10207","key":"10.1016\/j.clinre.2022.101976_bib0001","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S0140-6736(19)32319-0","article-title":"Colorectal cancer","volume":"394","author":"Dekker","year":"2019","journal-title":"Lancet"},{"issue":"12","key":"10.1016\/j.clinre.2022.101976_bib0002","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1002\/ijc.32055","article-title":"Global trends in colorectal cancer mortality: projections to the year 2035","volume":"144","author":"Araghi","year":"2019","journal-title":"Int J Cancer"},{"issue":"3","key":"10.1016\/j.clinre.2022.101976_bib0003","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3390\/cells8030234","article-title":"Selected aspects of chemoresistance mechanisms in colorectal carcinoma-A focus on epithelial-to-mesenchymal transition, autophagy, and apoptosis","volume":"8","author":"Skarkova","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.clinre.2022.101976_bib0004","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2019.107447","article-title":"5-fluorouracil and other fluoropyrimidines in colorectal cancer: past, present and future","volume":"206","author":"Vodenkova","year":"2020","journal-title":"Pharmacol Ther"},{"issue":"3","key":"10.1016\/j.clinre.2022.101976_bib0005","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.trecan.2019.02.003","article-title":"Polytherapy and targeted cancer drug resistance","volume":"5","author":"Chatterjee","year":"2019","journal-title":"Trends Cancer"},{"key":"10.1016\/j.clinre.2022.101976_bib0006","series-title":"The pharmacopoeia of the People\u2019s Republic of China. \u2160","first-page":"276","author":"National Pharmacopoeia Committee","year":"2020"},{"key":"10.1016\/j.clinre.2022.101976_bib0007","series-title":"Drugs and lactation database (LactMed)","year":"2006"},{"issue":"6","key":"10.1016\/j.clinre.2022.101976_bib0008","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/ptr.6054","article-title":"Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: review","volume":"32","author":"Soleimani","year":"2018","journal-title":"Phytother Res PTR"},{"issue":"11","key":"10.1016\/j.clinre.2022.101976_bib0009","doi-asserted-by":"crossref","first-page":"861","DOI":"10.7326\/M20-0990","article-title":"Effectiveness of curcuma longa extract for the treatment of symptoms and effusion-synovitis of knee osteoarthritis: a randomized trial","volume":"173","author":"Wang","year":"2020","journal-title":"Ann Intern Med"},{"issue":"2","key":"10.1016\/j.clinre.2022.101976_bib0010","first-page":"605","article-title":"Curcuma longa as medicinal herb in the treatment of diabet- IC complications","volume":"74","author":"Karlowicz-Bodalska","year":"2017","journal-title":"Acta Pol Pharm"},{"issue":"37","key":"10.1016\/j.clinre.2022.101976_bib0011","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.2174\/0929867324666161118095443","article-title":"Recent advances in obesity: the role of turmeric tuber and its metabolites in the prophylaxis and therapeutical strategies","volume":"25","author":"Jarz\u0105b","year":"2018","journal-title":"Curr Med Chem"},{"key":"10.1016\/j.clinre.2022.101976_bib0012","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113467","article-title":"A combination index and glycoproteomics-based approach revealed synergistic anticancer effects of curcuminoids of turmeric against prostate cancer PC3 cells","volume":"267","author":"Wei","year":"2021","journal-title":"J Ethnopharmacol"},{"issue":"54","key":"10.1016\/j.clinre.2022.101976_bib0013","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4103\/pm.pm_270_17","article-title":"Herbal medicines showing synergistic effects with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against A549 TRAIL-resistant lung cancer cells: a screening study","volume":"14","author":"Chiang","year":"2018","journal-title":"Pharmacogn Mag"},{"issue":"4","key":"10.1016\/j.clinre.2022.101976_bib0014","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3390\/medicina55040090","article-title":"The influence of curcumin on the downregulation of MYC, insulin and IGF-1 receptors: a possible mechanism underlying the anti-growth and anti-migration in chemoresistant colorectal cancer cells","volume":"55","author":"Hosseini","year":"2019","journal-title":"Medicina"},{"issue":"5","key":"10.1016\/j.clinre.2022.101976_bib0015","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/ptr.6035","article-title":"Superior anticancer activity is demonstrated by total extract of Curcuma longa L. as opposed to individual curcuminoids separated by centrifugal partition chromatography","volume":"32","author":"Kukula-Koch","year":"2018","journal-title":"Phytother Res"},{"key":"10.1016\/j.clinre.2022.101976_bib0016","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bcp.2016.09.024","article-title":"Andrographolide reversed 5-FU resistance in human colorectal cancer by elevating BAX expression","volume":"121","author":"Wang","year":"2016","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.clinre.2022.101976_bib0017","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: a database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J Cheminform"},{"issue":"11","key":"10.1016\/j.clinre.2022.101976_bib0018","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1016\/j.bbamcr.2016.08.009","article-title":"Decellularized matrices as in vitro models of extracellular matrix in tumor tissues at different malignant levels: mechanism of 5-fluorouracil resistance in colorectal tumor cells","volume":"1863","author":"Hoshiba","year":"2016","journal-title":"Biochim Biophys Acta"},{"issue":"9","key":"10.1016\/j.clinre.2022.101976_bib0019","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41419-020-02998-6","article-title":"PI3K\/AKT pathway as a key link modulates the multidrug resistance of cancers","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis"},{"issue":"7","key":"10.1016\/j.clinre.2022.101976_bib0020","first-page":"2473","article-title":"Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells","volume":"29","author":"Doan","year":"2009","journal-title":"Anticancer Res"},{"issue":"10","key":"10.1016\/j.clinre.2022.101976_bib0021","doi-asserted-by":"crossref","first-page":"e44176","DOI":"10.1371\/journal.pone.0044176","article-title":"TLR-4 signalling accelerates colon cancer cell adhesion via NF-\u03baB mediated transcriptional up-regulation of Nox-1","volume":"7","author":"O'Leary","year":"2012","journal-title":"PLoS One"},{"issue":"5","key":"10.1016\/j.clinre.2022.101976_bib0022","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1272\/jnms.JNMS.2020_87-508","article-title":"Drug resistance in cancer therapy and the role of epigenetics","volume":"87","author":"Asano","year":"2020","journal-title":"J Nippon Med Sch"},{"key":"10.1016\/j.clinre.2022.101976_bib0023","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ejmech.2019.05.027","article-title":"Natural products as multidrug resistance modulators in cancer","volume":"176","author":"Kumar","year":"2019","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.clinre.2022.101976_bib0024","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jep.2017.03.051","article-title":"Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes","volume":"203","author":"To","year":"2017","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.clinre.2022.101976_bib0025","doi-asserted-by":"crossref","first-page":"820","DOI":"10.3389\/fphar.2019.00820","article-title":"Formononetin: a review of its anticancer potentials and mechanisms","volume":"10","author":"Tay","year":"2019","journal-title":"Front Pharmacol"},{"issue":"10","key":"10.1016\/j.clinre.2022.101976_bib0026","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1124\/dmd.120.000050","article-title":"The effects of traditional chinese medicine on P-glycoprotein-mediated multidrug resistance and approaches for studying the herb-P-glycoprotein interactions","volume":"48","author":"Cao","year":"2020","journal-title":"Drug Metab Dispos Biol Fate Chem"},{"key":"10.1016\/j.clinre.2022.101976_bib0027","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.111078","article-title":"Molecular targets for the management of cancer using Curcuma longa Linn. phytoconstituents: a review","volume":"135","author":"Sultana","year":"2021","journal-title":"Biomed Pharmacother"},{"issue":"10","key":"10.1016\/j.clinre.2022.101976_bib0028","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1002\/ptr.6703","article-title":"Curcumin effect on cancer cells' multidrug resistance: an update","volume":"34","author":"Keyvani-Ghamsari","year":"2020","journal-title":"Phytother Res"},{"key":"10.1016\/j.clinre.2022.101976_bib0029","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.lfs.2017.09.035","article-title":"Chemopreventive effects of FITOPROT against 5-fluorouracil-induced toxicity in HaCaT cells","volume":"193","author":"Dos Santos Filho","year":"2018","journal-title":"Life Sci"},{"issue":"4","key":"10.1016\/j.clinre.2022.101976_bib0030","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.amjsurg.2005.11.009","article-title":"Colon cancer and apoptosis","volume":"191","author":"Huerta","year":"2006","journal-title":"Am J Surg"},{"issue":"35","key":"10.1016\/j.clinre.2022.101976_bib0031","doi-asserted-by":"crossref","first-page":"59950","DOI":"10.18632\/oncotarget.19048","article-title":"The molecular mechanisms of chemoresistance in cancers","volume":"8","author":"Zheng","year":"2017","journal-title":"Oncotarget"},{"issue":"10","key":"10.1016\/j.clinre.2022.101976_bib0032","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1124\/dmd.120.000182","article-title":"Natural products: experimental approaches to elucidate disposition mechanisms and predict pharmacokinetic drug interactions","volume":"48","author":"Paine","year":"2020","journal-title":"Drug Metab Dispos Biol Fate Chem"},{"issue":"1","key":"10.1016\/j.clinre.2022.101976_bib0033","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s11655-019-3064-0","article-title":"Network pharmacology in research of Chinese medicine formula: methodology, application and prospective","volume":"26","author":"Luo","year":"2020","journal-title":"Chin J Integr Med"},{"key":"10.1016\/j.clinre.2022.101976_bib0034","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.lfs.2016.05.012","article-title":"TLR4 siRNA inhibits proliferation and invasion in colorectal cancer cells by downregulating ACAT1 expression","volume":"155","author":"Ye","year":"2016","journal-title":"Life Sci"},{"issue":"1","key":"10.1016\/j.clinre.2022.101976_bib0035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0189582","article-title":"Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer","volume":"13","author":"Makondi","year":"2018","journal-title":"PLoS One"},{"issue":"28","key":"10.1016\/j.clinre.2022.101976_bib0036","doi-asserted-by":"crossref","first-page":"19911","DOI":"10.18632\/oncotarget.24952","article-title":"Over-activation of AKT signaling leading to 5-Fluorouracil resistance in SNU-C5\/5-FU cells","volume":"9","author":"Kim","year":"2018","journal-title":"Oncotarget"},{"issue":"6","key":"10.1016\/j.clinre.2022.101976_bib0037","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.3390\/cancers14061538","article-title":"In vivo and in vitro enhanced tumoricidal effects of metformin, active vitamin D(3), and 5-fluorouracil triple therapy against colon cancer by modulating the PI3K\/Akt\/PTEN\/mTOR network","volume":"14","author":"Almaimani","year":"2022","journal-title":"Cancers"}],"container-title":["Clinics and Research in Hepatology and Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2210740122001103?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2210740122001103?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:33:40Z","timestamp":1761896020000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2210740122001103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["S2210740122001103"],"URL":"https:\/\/doi.org\/10.1016\/j.clinre.2022.101976","relation":{},"ISSN":["2210-7401"],"issn-type":[{"value":"2210-7401","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Curcumae longae Rhizoma (Jianghuang) extract reverses the 5-Fluoruracil resistance in colorectal cancer cells via TLR4\/PI3K\/Akt\/mTOR pathway","name":"articletitle","label":"Article Title"},{"value":"Clinics and Research in Hepatology and Gastroenterology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clinre.2022.101976","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"101976"}}