UDCA has been administered in Chinese traditional medicine as a remedy for liver diseases and other disorders in the form of black bear's bile since the time of the T'ang dynasty (618-907AD) and was reestablished in the late 1950s in Japan as a choleretic agent with gallstonedissolving and anticholestatic properties. In the Western literature, the beneficial effects of UDCA on serum liver tests for patients with hepatic disorders were first reported in the 1980s [213, 214] , and UDCA has since been established for the treatment of PBC. Today, it is the only FDA-approved drug and standard therapy for PBC. UDCA was shown to improve serum biochemical markers such as bilirubin, AP, γGT, cholesterol, and IgM levels [215] [216] [217] [218] [219] [220] . UDCA may slow down histologic progression to liver cirrhosis [219, 221] , improve quality of life, survival free of transplant, and overall survival [11] [12] [13] [14] 222] . It is safe and side effects are few [223] . However, the mechanisms of action of UDCA in chronic cholestasis remain enigmatic [224] . About a third of patients is not sufficiently controlled with UDCA monotherapy [12, 13] , which drives the search for additional therapeutic approaches (Fig. 1) .