From dried bear bile to molecular investigation of differential effects of bile acids in ex vivo and in vitro models of myocardial dysfunction: relevance for neuroinflammation

Bile acids have been known to have both beneficial and detrimental effects on heart function, and as a consequence this can affect the brain. Inflammation is a key factor linking the heart and the brain, bile acids can reduce inflammation in the heart and, as a consequence, neuroinflammation, which may be due to the activation of different peripheral and central cellular and molecular mechanisms. Herein, we compile data published so far and summarise evidence demonstrating the effects of bile acids on myocardial cell viability and function, and its related mechanisms, in ex vivo and in vitro studies conducted in homeostatic state or in models of cardiovascular diseases. Studies show that ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) do not affect the viability or contraction of cardiomyocytes in homeostatic state, and while UDCA has the capability to prevent the effect of hypoxia on reduced cell viability and beating rate, TUDCA can protect endoplasmic reticulum (ER) stress-induced apoptosis and cardiac contractile dysfunction. In contrast, deoxycholic acid (DCA) decreases contraction rate in homeostatic state, but it also prevents hypoxia-induced inflammation and oxidative stress, whereas lithocholic acid (LCA) can rescue doxazosin-induced apoptosis. Moreover, glycodeoxycholic acid (GDCA), cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA) decrease contraction, whereas CDCA decreases cell viability in homeostatic conditions. The mechanisms underlying the aforementioned contrasting effects involve a differential regulation of the TGR5, M₂R and FXR receptors, as well as the cAMP signalling pathway. Overall, this review confirms the therapeutic potential of certain types of bile acids: UDCA, TUDCA, and potentially LCA, in cardiovascular diseases. By reducing inflammation in the heart, bile acids can improve heart-brain communication and promote overall health. Additional investigations are required to better elucidate mechanisms of action and more personalized clinical therapeutic doses.