Choleretic action of diosgenin is based upon the increases in canalicular membrane fluidity and transporter activity mediating bile acid independent bile flow.
It is known that diosgenin alters the lipid composition of hepatic plasma membranes as well as bile lipids. We recently reported that changes in the lipid composition of the canalicular membrane bilayer were associated with alterations of membrane fluidity. Therefore, the present study was performed to determine the effect of diosgenin on bile secretion, focusing on canalicular membrane composition, membrane fluidity, transporter expression, and transporter activity. METHODS: SD rats were fed a diet with or without diosgenin. Bile duct cannulation was done and the bile acid pool was depleted, followed by infusion of sodium taurocholate for 120 min to collect bile samples. Bile flow and the biliary output of cholesterol (Ch), phospholipids, bile salt, and total glutathione (GSH+GSSG) were estimated. Liver canalicular membrane vesicles (CMV) were prepared for the assessment of lipid composition, ATP-dependent transporters, and membrane fluidity. RESULTS: Bile flow, especially bile acid-independent fraction, was increased significantly by diosgenin. Biliary output of Ch and total glutathione were significantly increased by diosgenin. CMV fluidity and Mrp2 expression were increased by diosgenin. CONCLUSION: The fact that diosgenin increased bile flow and biliary cholesterol and glutathione output indicates a choleretic action along with enhancement of solute secretion. The increase of CMV fluidity and Mrp2 suggests that the choleretic action of diosgenin was based upon both the direct stimulation of transporter expression and indirect transporter activation by an increase of membrane fluidity.
Yamaguchi
Atsushi
A
First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, 734-8551, Hiroshima, Japan
Tazuma
Susumu
S
Ochi
Hidenori
H
Chayama
Kazuaki
K