{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T17:22:40Z","timestamp":1768843360069,"version":"3.49.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric cancer (GC) is a complex pathogenesis closely related to various signalling pathways. Esculin, as a natural compound, possesses anti\u2010oxidation, anti\u2010inflammatory, and anti\u2010tumour influences, and has shown promising application prospects in research on colorectal cancer (CRC) and others. However, the specific impact of Esculin on GC remains unclear. This article explores the action mechanism of Esculin in gastric cancer, which not only helps to understand its anti\u2010cancer properties but may also offer novel approaches and strategies for treating GC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the CCK\u20108 method to screen the concentration of Esculin that does not affect the viability of normal gastric mucosal cells GES\u20101. At this concentration, the changes in viability, proliferation level, migration ability, invasion ability, and apoptosis level of HGC\u201027 and AGS were measured. The levels of related proteins were detected through Western blot. Subsequent use of the glycolysis inhibitor 3\u2010BrPA, the Wnt signalling pathway activator SKL2001, and the inhibitor LiCl interfered with GC cells. The impact of Esculin on aerobic glycolysis in cells was assessed by measuring glucose uptake levels, pyruvate production levels, lactate generation levels, ATP production levels, and extracellular acidification rate (ECAR). The regulatory effect of Esculin on the Wnt\/\u03b2\u2010catenin\/HIF\u20101\u03b1 pathway was evaluated through immunofluorescence and Western blot. Injecting HGC\u201027 cells to build a xenograft tumour model and evaluating the effect of Esculin gavage on tumour growth in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Esculin at concentrations of 0, 20, 40, and 80\u2009\u03bcM is non\u2010toxic to GES\u20101. An increase in the concentration of Esculin correlates with a continuous decline in the viability of four GC cell lines, with GC cells showing the highest significance. The levels of proliferation, migration, and invasion in both cell lines significantly decrease with increasing concentrations of Esculin, while the apoptosis rate significantly increases. 80\u2009\u03bcM of Esculin can significantly inhibit glucose absorption, pyruvate production, lactate, and ATP generation in cells, leading to a significant decrease in ECAR; at the same time, it significantly inhibits the expression of proteins in the Wnt\/\u03b2\u2010catenin\/HIF\u20101\u03b1 signalling pathway. Administering 20\u2009mg\/kg of Esculin by gavage can significantly suppress tumour growth in mice, concurrently leading to a reduction of proteins associated with the Wnt\/\u03b2\u2010catenin\/HIF\u20101\u03b1 pathway within the tumour tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Esculin inhibits aerobic glycolysis in cells via the Wnt\/\u03b2\u2010catenin\/HIF\u20101\u03b1 pathway, alleviating the progress of GC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70096","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T06:47:07Z","timestamp":1764830827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Esculin Facilitates Aerobic Glycolysis via the Wnt\/\u03b2\u2010Catenin\/\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1 Pathway to Reduce the Progression of Gastric Cancer"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6341-0701","authenticated-orcid":false,"given":"Qing","family":"Shang","sequence":"first","affiliation":[{"name":"Department of General Surgery Xinxiang Central Hospital  Xinxiang Henan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Xinxiang Central Hospital  Xinxiang Henan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Xinxiang Central Hospital  Xinxiang Henan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haipeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Xinxiang Central Hospital  Xinxiang Henan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00726-3"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1004383"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1399679"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-2545"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-21-655"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04859-w"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-024-03396-0"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1404172"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7470"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpca.1c06369"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118139"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14081043"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.08.024"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.797605"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.116563"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.128848"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12089"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01825-3"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00990-3"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-3074"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-024-09694-0"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280572"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.881252"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000040273"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2023.02.039"},{"issue":"5","key":"e_1_2_14_27_1","first-page":"727","article-title":"Research Progress on the Biological Effects of HIF\u20101\u03b1 on Follicle Development and Ovulation","volume":"75","author":"Ma L. 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