Table 2.
The summary of UDCA mechanisms of action with the experimental models/subjects and concentrations used.
| Model | Suggested UDCA Mechanism of Action | Concentration of UDCA Used | References |
|---|---|---|---|
| In vitro rat model of the fetal heart | UDCA induces cAMP release without any effects on contraction rate, which is mediated through TGR5. | 100 µM | [63] |
| In vitro rat model of the cholestatic fetal heart | UDCA activates KATP channels and improves intracellular calcium level. | 100 µM | [91] |
| In vitro rat model of ischemia–reperfusion | UDCA reduces LDH release and enhances the recovery of cardiac contractile function during reperfusion. | 80–160 µM | [101] |
| In vitro and in vivo rat models of ischemia–reperfusion | UDCA inhibits the opening of MPTP and Bcl-2 via PI3K/Akt pathway. | 40 mg/kg | [102] |
| In vivo rat model of metabolic syndrome | UDCA reduces uric acid level and improves insulin resistance of fructose-induced metabolic syndrome rat. | 150 mg/kg | [103] |
| In vitro rat model of hypoxic cells | UDCA inhibits HIF-1α expression, upregulates ERK 1/2, and Akt while downregulating caspase-9 and reactive oxygen species (ROS) generation in cobalt chloride (CoCl2)-induced hypoxic CMs. | 100 µM | [93,104,105] |
| In vivo mouse model of diabetic atherosclerosis | UDCA exerts antiatherogenic activity through reduction of endoplasmic reticulum stress, receptor for advanced glycation end product (RAGE) signaling, and proinflammatory responses of ROS and Nf-κB. | 100 µM | [106] |
| Patients with coronary heart disease | UDCA improves endothelium- and NO-independent vasodilatation that maintains the arterial flow in patients with heart failure. | 13–19 mg/kg | [107] |
| Patients with chronic heart failure | UDCA improves liver function and lowers the level of γ-glutamyl transferase, aspartate transaminase, and soluble TNF-α receptor 1. | 1280 µM | [108] |
UDCA, ursodeoxycholic acid; cAMP, cyclic adenosine monophosphate; TGR5, Takeda G-protein-coupled bile acid receptor 1; KATP, ATP-sensitive potassium channel; LDH, lactate dehydrogenase; MPTP, mitochondrial permeability transition pore; Bcl-2, B-cell lymphoma 2; PI3K, phhosphoinositide 3-kinase; HIF-1α, hypoxia inducible factor 1 alpha; ERK 1/2, extracellular regulated kinase; Akt, protein kinase B; CoCl22, cobalt chloride; CMs, CMs; ROS, reactive oxygen species; Nf-κB, nuclear factor kappa B; NO, nitric oxide; TNF-α receptor 1, tumor necrosis factor 1.