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Anacardic acid (AA) shows broad pharmacological properties, but its effect on DCM was unknown. This study aims to investigate the effect and molecular action of AA on DCM. KKAy mice, a model of spontaneous type 2 diabetes, were fed a high\u2010fat diet, and were subsequently administered with AA by gavage at 5\u00a0mg\/kg for 14 weeks. AA attenuated cardiac dysfunction, pathological injuries, inflammation, fibrosis, oxidative stress, and apoptosis. Mechanistically, AA was enriched in the colon, but not serum and heart, improving colonic histopathological scores, enhancing colonic tight junction protein expression and reducing serum lipopolysaccharide level, suggesting colonic epithelial barrier integrity (CEBI) as a key target of AA. In vitro experiment employed high glucose and palmitic acid\u2010challenged colonic epithelial cells as a cell model of CEBI, showing that AA at 5 \u00b5mol\/L reversed the impaired expression of tight junction proteins. RNA\u2010sequencing identified\n                    <jats:italic>Pde2a<\/jats:italic>\n                    gene to be significantly inhibited by AA. Lentivirus\u2010induced\n                    <jats:italic>Pde2a<\/jats:italic>\n                    overexpression in colonic epithelial cells abolished the protective effect of AA on CEBI. The present study reports that AA enhances CEBI to attenuate DCM, possibly through inhibiting colonic epithelial expression of\n                    <jats:italic>Pde2a<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70464","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:06:57Z","timestamp":1776334017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anacardic Acid Inhibits\n                    <i>Pde2a<\/i>\n                    to Enhance Colonic Epithelial Barrier Integrity in the Improvement of Diabetic Cardiomyopathy"],"prefix":"10.1002","volume":"70","author":[{"given":"Rui","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health Cheeloo College of Medicine Shandong University  Jinan Shandong China"},{"name":"Shandong Provincial Engineering and Technology 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