After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease.
Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.
2. Amaral J., Viana R., Ramalho R. et al. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J. Lipid Res. 2009. No 50. P. 1721–1734.
3. Copple B., Li T. Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules. Pharmacol Res. 2016. No 104. P. 9–21.
4. Daruich А., Picard Е., Boatright J., Behar-Cohen F. Review: The bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease. Molecular Vision. 2019. No 25. Р. 610–624.
5. Hu J., Hong W., Yao K. et al. Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway. World J. Gastroenterol. 2019. Vol. 25. No 12. P. 1492–1501.
6. Mertens K., Kalsbeek A., Soeters M., Eggink H. Bile acid signaling pathways from the enterohepatic circulation to the central nervous system. Front Neurosci. 2017. No 11. Р. 617.
7. Monte M., Marin J., Antelo A., Vazquez-Tato J. Bile acids: chemistry, physiology, and pathophysiology. World J. Gastroenterol. 2009. No 15. Р. 804–816.
8. Mouillot Т., Beylot М., Drai J. et al. Effect of bile acid supplementation on endogenous lipid synthesis in patients with short bowel syndrome: a pilot study. Clinical Nutrition. 2019. Article in press.
9. Mueller М., Thorell А., Claudel Т. et al. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. Journal of Hepatology. 2015. Vol. 62. Р. 1398–1404.
10. Reinicke M., Schröter J., Müller-Klieser D. et al. Free oxysterols and bile acids including conjugates — Simultaneous quantification in human plasma and cerebrospinal fluid by liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta. 2018. No 1037. P. 245–255.
11. Simental-Mendía L., Simental-Mendía М., Sánchez-García А. et al. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids in Health and Disease. 2019. No 18. P. 88.
12. Tonin F., Arends I. W. C. E. Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review. Beilstein J. Org. Chem. 2018. No 14. Р. 470–483.
13. 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. No 10. P. 842.