{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:25:34Z","timestamp":1787217934925,"version":"build-2736575974"},"reference-count":159,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, despite significant advances in diagnostics and pharmacotherapy. This persistent burden has shifted attention toward adjunct therapeutic strategies targeting key mechanisms of myocardial and vascular injury, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, apoptosis, inflammation, endothelial dysfunction, and metabolic dysregulation. A particular interest of contemporary research is focused on bile acid (BA) signaling through nuclear and membrane receptors, primarily the Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), as central regulators of metabolic, inflammatory, and vascular responses. Ursodeoxycholic acid (UDCA), a hydrophilic BA widely used to treat hepatobiliary disorders, has emerged as a potential modulator of cardiometabolic processes. UDCA exerts direct effects through low-affinity but functionally relevant activation of the TGR5 receptor, as well as indirect effects through alterations in BA pool composition, thereby influencing FXR\/TGR5 signaling pathways. Experimental studies suggest that UDCA reduces oxidative stress, stabilizes mitochondrial function, alleviates ER stress, suppresses apoptosis and inflammation, and improves endothelial function and nitric oxide (NO) bioavailability. Despite promising mechanistic evidence, currently available clinical data remain limited and are largely based on small studies and surrogate biomarkers, without confirmation of benefits in terms of major cardiovascular outcomes. This review summarizes current knowledge regarding the role of UDCA in the modulation of BA receptor signaling and its potential relevance for cardiovascular protection.<\/jats:p>","DOI":"10.3389\/fphar.2026.1901120","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:46:31Z","timestamp":1787215591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ursodeoxycholic acid as a potential cardioprotective agent: molecular mechanisms, experimental evidence, and clinical perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Tatjana","family":"Milivojac","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"Department of Pathophysiology, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nata\u0161a","family":"Stojakovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momir","family":"Mikov","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milorad","family":"Vujni\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranko","family":"\u0160krbi\u0107","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"Academy of Science and Arts of the Republic of Srpska, Department of Medical Science","place":["Banja Luka, Bosnia and Herzegovina"]},{"name":"Department of Pathologic Physiology, First Moscow State Medical University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.mam.2017.04.001","article-title":"Bile acids and bariatric surgery","volume":"56","author":"Albaugh","year":"2017","journal-title":"Mol. 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