Pharmacology and Toxicology of Chenodeoxycholic Acid: Chenodeoxycholic acid (CDCA) main role is to reduce the saturation of bile cholesterol, after the vast majority of patients taking CDCA (when CDCA bile bile salt accounted for 70%), lipid micelles recovery state, cholesterol level It is not saturated, so that the stones of cholesterol dissolved off. Large doses of CDCA (daily 10 ~ 15mg / kg) can inhibit the synthesis of cholesterol, and increase the secretion of bile in patients with cholelithiasis, but the bile salts and phospholipid secretion remains unchanged. Larger doses, the incidence of diarrhea, the liver has some toxicity.
We did experiments with rats. Male Wistar rats (8-week-old; n=40) were randomized into the following four groups (n=10): Untreated control, Chenodeoxycholic acid-treated, T2DM, and CDCA-treated T2DM. To establish the T2DM model, the rats were fed a high-fat diet (HFD) for 4 weeks and received a single low-dose intraperitoneal injection of streptozotocin (30 mg/kg), followed by an additional 4 weeks of HFD feeding. CDCA was administrated (10 mg/kg/d) intraperitoneally for 10 days. Reverse transcription-quantitative polymerase chain reaction and western blotting assays were performed to determine the RNA and protein expression of FXR, phosphoenolpyruvate carboxykinase, G6Pase, proliferator-activated receptor-γ coactivator-1 and short heterodimer partner in rat liver tissue. Farnesoid X receptor (FXR) is an important regulator of glucose and lipid homeostasis. However, the exact role of FXR in diabetes remains to be fully elucidated. The present study examined the effects of Chenodeoxycholic acid (CDCA), an agonist of FXR, on metabolism profile in a rat model of type 2 diabetes mellitus (T2DM).
The results revealed that FXR activation by Chenodeoxycholic acid did not reduce body weight, but it lowered the plasma levels of fasting glucose, insulin and triglycerides in the T2DM rats. CDCA administration reversed the downregulation of the mRNA and protein expression of FXR in the T2DM rat liver tissue samples. Furthermore, treatment with CDCA reduced the mRNA and protein expression levels of phosphoenolpyruvate carboxykinase, glucose 6-phosphatase and peroxisome proliferator-activated receptor-γ coactivator-1 in the liver tissue samples of the T2DM rats. By contrast, CDCA treatment increased the mRNA and protein expression levels of short heterodimer partner in the liver tissue samples of the T2DM rats. In conclusion, FXR agonist treatment induces beneficial effects on metabolism in the rat T2DM model. In conclusion, the present study indicated that the FXR agonist may be useful for the treatment of T2DM and hypertriglyceridemia. In summary, Chenodeoxycholic Acid is useful for the treatment.