Diosgenin stimulation of fecal cholesterol excretion in mice is not NPC1L1 dependent

Diosgenin exists in some food supplements and herbal medicines and lowers plasma cholesterol by increasing fecal cholesterol excretion. It is believed that diosgenin promotes fecal cholesterol excretion by stimulating biliary cholesterol secretion and decreasing intestinal cholesterol absorption. Niemann-Pick C1-like 1 (NPC1L1) was recently identified as an essential protein for intestinal cholesterol absorption. To determine the relative contribution of biliary secretion and intestinal absorption of cholesterol in diosgenin-stimulated fecal cholesterol excretion, wild-type (WT) and NPC1L1-knockout (L1KO) mice were fed a diet with or without 1% diosgenin. Fecal cholesterol excretion (μmol/day/100 g body weight) increased in diosgenin-fed WT and L1KO mice from 4.2 to 52 and from 63 to 140, respectively. Surprisingly, this increase in diosgenin-treated versus untreated L1KO mice (77) was even greater than that seen in diosgenin-treated versus untreated WT mice (47.8). Additionally, WT and L1KO mice fed the diosgenin diet had similar increases in biliary cholesterol concentration, despite unaltered hepatic expression of the hepatobiliary cholesterol transporter, ATP binding cassette transporters G5 and G8. Facilitated cholesterol excretion in diosgenin-treated WT and L1KO mice was associated with decreased hepatic and plasma cholesterol and increased liver expression of cholesterol synthetic genes. In contrast, diosgenin had no effect on the intestinal expression of NPC1L1 and cholesterol synthetic genes. In an in vitro assay, diosgenin was unable to block NPC1L1-dependent cholesterol uptake. In conclusion, diosgenin stimulation of fecal cholesterol excretion is independent of NPC1L1-mediated cholesterol absorption

Asparagus Root Regulates Cholesterol Metabolism and Improves Antioxidant Status in Hypercholesteremic Rats

Hyperlipidemia/hypercholesteremia are major risk factors for atherosclerosis and cardiovascular diseases. Root of Asparagus racemosus (AR) is widely used in Ayurvedic system of medicine in India and is known for its steroidal saponin content. This study was designed to investigate the hypocholesteremic and antioxidant potential of AR root in both normo- and hypercholesteremic animals. Normal and hypercholesteremic male albino rats were administered with root powder of AR (5 and 10 g% dose levels) along with normal and hypercholesteremic diets, respectively, for a duration of 4 weeks. Plasma and hepatic lipid profiles, fecal sterol, bile acid excretion and hepatic antioxidant activity were assessed. Inclusion of AR root powder in diet, resulted in a dose-dependant reduction in plasma and hepatic lipid profiles, increased fecal excretion of cholesterol, neutral sterol and bile acid along with increases in hepatic HMG-CoA reductase activity and bile acid content in hypercholesteremic rats. Further, AR root also improved the hepatic antioxidant status (catalase, SOD and ascorbic acid levels). No significant changes in lipid and antioxidant profiles occurred in the normocholesteremic rats administered with AR root powder. AR root appeared to be useful as a dietary supplement that offers a protection against hyperlipidemia/hypercholesteremia in hypercholesteremic animals. The results of the present study indicate that the potent therapeutic phyto-components present in AR root i.e. phytosterols, saponins, polyphenols, flavonoids and ascorbic acid, could be responsible for increased bile acid production, elimination of excess cholesterol and elevation of hepatic antioxidant status in hypercholesteremic conditions