Pleiotropic effects of ursodeoxycholic acid

Main Article Content

Yu.М. Stepanov
А.V. Salenko


The article summarizes the literature data on the expansion of the range of application of ursodeoxycholic acid due to its various mechanisms of action. Almost 50-year history of the study of its properties has proven choleretic, litholytic, antiapoptotic, anti-inflammatory, immunomodulatory, cytoprotective, antifibrotic and hypocholesterolemic effects. In addition to the well-known functions of bile acids, their role has been shown as signa­ling, endocrine molecules that regulate glucose, lipids, and energy metabolism through pathways mediated by the activation of the nuclear receptor of the farnesoid X receptor and the cell surface G protein-coupled receptor, TGR5. The variety of nosological forms in which this substance can be successfully used is substantiated.

Article Details

How to Cite
Stepanov, Y., & Salenko А. (2021). Pleiotropic effects of ursodeoxycholic acid. GASTROENTEROLOGY, 55(2), 115–121.
Reviews and Lections


Monte MJ, Marin JJ, Antelo A, Vazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J Gastroenterol. 2009 Feb 21;15(7):804-816. doi:10.3748/wjg.15.804.

Kazyulin AN, Shestakov VA, Goncharenko AYu, Kalyagin IE, Pavleeva EE. Practice and prospects of clinical application of ursodeoxycholic acid preparations. RMJ. Medical Review. 2018;(3):45-52. (in Russian).

Daruich A, Picard E, Boatright JH, Behar-Cohen F. Review: The bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease. Mol Vis. 2019 Oct 14;25:610-624.

Mertens KL, Kalsbeek A, Soeters MR, Eggink HM. Bile acid signaling pathways from the enterohepatic circulation to the central nervous system. Front Neurosci. 2017 Nov 7;11:617. doi:10.3389/fnins.2017.00617.

Drapkina OM, Bueverova EL. Ursodeoxycholic acid: a therapeutic niche in an internist’s practice. Terapevticheskii arkhiv. 2015;87(4):84-90. (in Russian).

Minushkin ON, Frolova AA, Shindina TS, Kropova OE, Mikhailova EV. Ursodeoxycholic acid in the gastroenterological practice. RMJ. Medical Review. 2018;(1-1):18-22. (in Russian).

Zhang Y, Zheng X, Huang F, et al. Ursodeoxycholic Acid Alters Bile Acid and Fatty Acid Profiles in a Mouse Model of Diet-Induced Obesity. Front Pharmacol. 2019 Jul 25;10:842. doi:10.3389/fphar.2019.00842.

Vinnitskaya EV, Absandze KG, Arkhipova EV, et al. Primary Biliary Cholangitis and Ursodeoxycholic Acid: Therapy Progress and Challenges. Doctor Ru. 2019;(158):33-39. doi:10.31550/1727-2378-2019-158-3-33-39. (in Russian).

Beuers U, Hohenester S, de Buy Wenniger LJ, Kremer AE, Jansen PL, Elferink RP. The biliary HCO(3)(-) umbrella: a unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies. Hepatology. 2010 Oct;52(4):1489-1496. doi:10.1002/hep.23810.

Klabukov ID, Krasilnikova OA, Lyundup AV, Dyuzheva TG. Immunological causes of gallstone disease (original hypothesis). Experimental and Clinical Gastroenterology. 2018;(6):134-142. (in Russian).

Copple BL, Li T. Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules. Pharmacol Res. 2016 Feb;104:9-21. doi:10.1016/j.phrs.2015.12.007.

Mueller M, Thorell A, Claudel T, et al. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J Hepatol. 2015 Jun;62(6):1398-1404. doi:10.1016/j.jhep.2014.12.034.

Bogolyubova AV, Mayorov AY, Mishina EE, Schwartz AM, Belousov PV. Farnesoid X receptor (FXR) as a potential therapeutic target in nonalcoholic fatty liver disease and associated syndromes. Diabetes mellitus. 2017;20(6):449-453. doi:10.14341/DM9374. (in Russian).

Mosińska P, Szczepaniak A, Fichna J. Bile acids and FXR in functional gastrointestinal disorders. Dig Liver Dis. 2018 Aug;50(8):795-803. doi:10.1016/j.dld.2018.05.016.

Arab JP, Karpen SJ, Dawson PA, Arrese M, Trauner M. Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives. Hepatology. 2017 Jan;65(1):350-362. doi:10.1002/hep.28709.

Ichikawa R, Takayama T, Yoneno K, et al. Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway. Immunology. 2012 Jun;136(2):153-162. doi:10.1111/j.1365-2567.2012.03554.x.

Ðanić M, Stanimirov B, Pavlović N, et al. Pharmacological Applications of Bile Acids and Their Derivatives in the Treatment of Metabolic Syndrome. Front Pharmacol. 2018 Dec 3;9:1382. doi:10.3389/fphar.2018.01382.

Hu J, Hong W, Yao KN, Zhu XH, Chen ZY, Ye L. Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway. World J Gastroenterol. 2019 Mar 28;25(12):1492-1501. doi:10.3748/wjg.v25.i12.1492.

Cipriani S, Mencarelli A, Chini MG, et al. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011;6(10):e25637. doi:10.1371/journal.pone.0025637.

Kida T, Tsubosaka Y, Hori M, Ozaki H, Murata T. Bile acid receptor TGR5 agonism induces NO production and reduces monocyte adhesion in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1663-1669. doi:10.1161/ATVBAHA.113.301565.

Duboc H, Aelion H, Rainteau D, et al. Crosstalk between the hepatologist and the cardiologist: a future place for the lithocholic acid as a coronary atheroma risk factor? Hepatology. 2012 Dec;56(6):2426. doi:10.1002/hep.25839.

Thomas C, Gioiello A, Noriega L, et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009 Sep;10(3):167-177. doi:10.1016/j.cmet.2009.08.001.

Zvenigorodskaia LA, Mel'nikova NV. Lipid-lowering therapy in patients with non-alcoholic fatty liver disease: the place of hepatoprotectors. Consilium Medicum. Gastoenterology. 2009;(1):32-36. (in Russian).

Mouillot T, Beylot M, Drai J, et al. Effect of bile acid supplementation on endogenous lipid synthesis in patients with short bowel syndrome: A pilot study. Clin Nutr. 2020 Mar;39(3):928-934. doi:10.1016/j.clnu.2019.03.037.

Maevskaya MM. Features of the therapy of non-alcoholic fatty liver disease in comorbid patients. Meditsinskiy sovet. 2020;(21):136-143. doi:10.21518/2079-701X-2020-21-136-143. (in Russian).

Abdelkader NF, Safar MM, Salem HA. Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations. Mol Neurobiol. 2016 Mar;53(2):810-817. doi:10.1007/s12035-014-9043-8.

Cortez LM, Campeau J, Norman G, et al. Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease. J Virol. 2015 Aug;89(15):7660-7672. doi:10.1128/JVI.01165-15.