The Role of Bile Acid Receptors in Chronic Inflammatory Diseases

Abstract

With recent developments, biologic therapies has shown superior efficacy for rheumatic diseases compared with preexisting pharmacologic therapies, which are associated with high costs, non-response in certain patient groups, and severe adverse effects such as infections limiting their wide-spread use and revealing a need for the development of novel treatments. Since discovering the role of bile acid receptors in regulating inflammation, clinical trials evaluating the use of bile acid receptor agonists as a means to potentially treat various inflammatory disorders, such as alcoholic hepatitis, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis have been ongoing. This review summarizes the results of studies on the anti-inflammatory effects and mechanisms of bile acid receptors and the results of previous to date looking at the use of bile acid receptor agonists in animal models of inflammatory disorders and clinical trials. Furthermore, we present the potentials of the bile acid receptor agonists in the treatment of inflammatory rheumatic diseases, including rheumatoid arthritis. (J Rheum Dis 2017;24:253-260)

Synthesis of 12β-Methyl-18-nor-bile Acids

“…Both of these receptors have important physiological functions due to which they are pursued as potent therapeutic targets for the treatment of various liver and metabolic disorders. − Since their discovery, various bile acid analogues have emerged as potent agonists ( i.e. , 5–11 ; Figure ), and many of these are being evaluated in clinical and pre-clinical trials. ,− The 6α-ethyl-substituted analogue of CDCA ( 5 ), also known as obeticholic acid or INT-747, is of particular note as it was approved as a first-in-class FXR agonist by the US Food and Drug Administration (FDA) for the treatment of primary biliary cholangitis in 2016.…”