The hypocholesterolemic activity of Momordica charantia fruit is mediated by the altered cholesterol- and bile acid-regulating gene expression in rat liver.

Although many studies have demonstrated the hypocholesterolemic activity of Momordica charantia, also called bitter gourd fruit (BGF), the relative hypocholesterolemic mechanism is not fully understood. In the present study, we hypothesized that BGF alters hepatic gene expression of cholesterol- and bile acid-regulating proteins to improve blood cholesterol profiles. To clarify the mechanism, we fed 7-week-old male Wistar rats a high-cholesterol (HC) diet containing 5% BGF for 4 weeks and determined the cholesterol levels in the serum, liver and feces, concentrations of the fecal total bile acid, and the expression level of cholesterol- and bile acid-regulating genes. The HC diet with BGF supplementation showed a significant serum hypocholesterolemic activity compared with the HC diet without BGF. BGF intake also significantly increased the levels of fecal total bile acid, suggesting that BGF inhibited the reabsorption of bile acids into the intestine. Hepatic messenger RNA (mRNA) levels of small heterodimer partner (SHP) and liver receptor homolog-1, which are both involved in cholesterol 7α-hydroxylase (CYP7A1) regulation, were significantly decreased and increased, respectively, by BGF intake. In addition, BGF tended to increase the hepatic CYP7A1 mRNA level. Taken together, these results suggest that BGF not only decreases the reabsorption of bile acids into the intestine but also increases the conversion of cholesterol to bile acids by CYP7A1 up-regulation through the down-regulation of the hepatic farnesoid X receptor/SHP pathway.