Cholesterol-lowering effect of platycodin D in hypercholesterolemic ICR mice

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Abstract

This study investigates the in vivo hypocholesterolemic action of platycodin D and its in vitro evidence for the cholesterol-lowering properties. In order to examine the effects of platycodin D on hypercholesterolemia in male ICR mice, platycodin D with doses of 15, 30 or 50 mg/kg was orally administered for 8 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of triglyceride and different types of cholesterol in the serum, livers and feces were determined. The effects of platycodin D on cholesterol metabolism were further investigated with several in vitro assays, including antioxidant effect on low density lipoprotein oxidation, inhibition of human acyl-coenzyme A:cholesterol acyltransferase (hACAT) and serum lipoprotein associated-phospholipase A2 (Lp-PLA2), as well as the regulation of farnesoid X receptor. The formation of insoluble complex between platycodin D and cholesterol was also investigated. Following an eight week experimental period, the body weights of platycodin D-fed mice were less than those of control mice on a high cholesterol diet by 11.2 ± 5% (P < 0.01) with 15 mg/kg platycodin D, 11.7 ± 5% (P < 0.01) with 30 mg/kg platycodin D, and 23.4 ± 7.9% (P < 0.0001) with 50 mg/kg platycodin D, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Triglyceride and cholesterol concentrations were decreased in serums and livers, but increased in feces. Some of the in vitro observations revealed that the hypocholesterolemic effect of platycodin D is partly associated with inhibition to hACAT activity and antagonism to the farnesoid X receptor as well as the formation of insoluble complex with between platycodin D and cholesterol. Both in vivo and in vitro results demonstrate a potential value of platycodin D as a novel cholesterol-lowering and anti-atherogenic candidate.

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