{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T01:44:51Z","timestamp":1775180691846,"version":"3.50.1"},"reference-count":43,"publisher":"Baishideng Publishing Group Inc.","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n                  <jats:p>Esophageal adenocarcinoma (EAC) frequently arises from chronic exposure to acid and bile reflux, with secondary bile acids, such as deoxycholic acid (DCA), contributing to its pathogenesis through mechanisms involving reactive oxygen species (ROS), oxidative DNA damage, and resistance to apoptosis. The human endocannabinoid system (ECS) regulates diverse anti-inflammatory, antioxidant, and analgesic pathways implicated in disease modulation and may counteract the harmful effects of gastroesophageal reflux. Despite its therapeutic promise, effective pharmacological activation of the ECS remains challenging.<\/jats:p>\n                  <jats:p>AIM<\/jats:p>\n                  <jats:p>To evaluate whether specific cannabinoid-terpene combinations targeting the ECS could attenuate the mutagenic and cytotoxic effects of bile acid-induced stress in esophageal cell models, and to assess the clinical significance of ECS-related protein receptors in the progression of EAC.<\/jats:p>\n                  <jats:p>METHODS<\/jats:p>\n                  <jats:p>Human esophageal epithelial cells exposed to DCA, as well as a Barrett\u2019s esophagus cell line subjected to low potential of hydrogen and a bile acid cocktail, were treated with various ratios of phyto-cannabinoids and terpenes. Endpoints included DNA damage, mitochondrial membrane potential, and ROS production to identify optimal compound combinations. Expression of ECS-related receptor proteins in clinical samples was assessed by immunohistochemistry.<\/jats:p>\n                  <jats:p>RESULTS<\/jats:p>\n                  <jats:p>A 1:5 ratio of cannabigerol to phytol significantly reduced DCA-induced DNA damage, preserved mitochondrial membrane potential, and decreased ROS levels. This combination also promoted apoptosis in damaged cells and reduced mutagenicity. Analysis of patient samples demonstrated that expression of the ECS-associated receptor protein CB1 correlated with EAC progression, indicating a broader clinical role for ECS modulation in cancer prevention.<\/jats:p>\n                  <jats:p>CONCLUSION<\/jats:p>\n                  <jats:p>Modulation of the ECS using systematically selected cannabinoid-terpene ratios can attenuate bile acid-induced esophageal damage and may reduce carcinogenic progression. These findings support further in vivo  studies and raise the possibility of expanding cannabinoid-terpene therapeutics to other diseases with comparable pathogenic mechanisms.<\/jats:p>","DOI":"10.3748\/wjg.v32.i14.111455","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:50:02Z","timestamp":1775177402000},"source":"Crossref","is-referenced-by-count":0,"title":["Optimal cannabinoid-terpene combination ratios suppress mutagenicity of gastric reflux in normal and metaplastic esophageal cells"],"prefix":"10.3748","volume":"32","author":[{"given":"Aaron","family":"Goldman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana A","family":"Karpova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leutz","family":"Buon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masood A","family":"Shammas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus H","family":"Frank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha Y","family":"Frank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2060","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06042.x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.10.006"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000037433"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.09.046"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3033206"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.041525"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2004.08.001"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1325"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M062653"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023835"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s0891-5849(00)00317-8"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/s0960-9822(02)00684-x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X08102044"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.01.017"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2174\/1874473710902010051"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1187"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/157015912800604515"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600646R"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00515.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12049"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26983"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1312"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-2999(98)00392-6"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.907579"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/ph17111543"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.962922"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00461.2010"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2490"},{"key":"B29","unstructured":"Stoner GD, Kaighn ME, Reddel RR, Resau JH, Bowman D, Naito Z, Matsukura N, You M, Galati AJ, Harris CC. 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