{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:57:00Z","timestamp":1791827820654,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Ursodeoxycholic acid (UDCA) is the first line therapy for the treatment of cholestatic and autoimmune liver diseases. Its clinical use is currently limited by a significant proportion of non-responder patients. Polyunsaturated fatty acids (n-3 PUFAs) possess important anti-inflammatory properties and protect liver cells against bile acid (BA)-induced toxicity. The present study was designed to rapidly evaluate whether combining n-3 PUFAs (i.e., eicosapentaenoic [EPA] and docosahexaenoic [DHA] acids) to UDCA would provide additional benefits when compared to the drug alone. The parameters evaluated were (i) the expression of genes governing BA synthesis, transport, and metabolism; (ii) the prevention of BA-induced apoptosis and endoplasmic reticulum (ER)-stress; and (iii) the control of BA- and LPS-dependent inflammation. In the absence of n-3 PUFAs, most of the parameters investigated were unaffected by UDCA or were only altered by the higher dose (500 \u00b5M) of the drug. By contrast, in the presence of EPA\/DHA (50\/50 \u00b5M), all parameters showed a strongly improved response and the lowest UDCA dosage (50 \u00b5M) provided equal or better benefits than the highest dose used alone. For example, the combination EPA\/DHA + UDCA 50 \u00b5M caused comparable down-regulation of the CYP7A1 gene expression and of the BA-induced caspase 3 activity as observed with UDCA 500 \u00b5M. In conclusion, these results suggest that the addition of n-3 PUFAs to UDCA may improve the response to the drug, and that such a pharmaco-nutraceutical approach could be used in clinic to open the narrow therapeutic dose of UDCA in cholestatic liver diseases.<\/jats:p>","DOI":"10.3390\/nu13082617","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T21:21:21Z","timestamp":1627593681000},"page":"2617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid"],"prefix":"10.3390","volume":"13","author":[{"given":"Ariane","family":"Th\u00e9rien","sequence":"first","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Faculty of Pharmacy, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-6333","authenticated-orcid":false,"given":"Anna","family":"Cie\u015blak","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Faculty of Pharmacy, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Verreault","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Perreault","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Trottier","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Gobeil","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7017-5848","authenticated-orcid":false,"given":"Marie-Claude","family":"Vohl","sequence":"additional","affiliation":[{"name":"Centre Nutrition, Sant\u00e9 et Soci\u00e9t\u00e9 (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-1134","authenticated-orcid":false,"given":"Olivier","family":"Barbier","sequence":"additional","affiliation":[{"name":"CHU de Qu\u00e9bec Research Center, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Faculty of Pharmacy, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"Centre Nutrition, Sant\u00e9 et Soci\u00e9t\u00e9 (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1053\/jhep.2002.36088","article-title":"Ursodeoxycholic acid in cholestatic liver disease: Mechanisms of action and therapeutic use revisited","volume":"36","author":"Paumgartner","year":"2002","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1042\/CS20110184","article-title":"Ursodeoxycholic acid in cholestasis: Linking action mechanisms to therapeutic applications","volume":"121","author":"Roma","year":"2011","journal-title":"Clin. 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