Studing of Polygonum cuspidatum on the Farnesoid X Receptor and Bile Acids Synthesis in Rodent Model of Obesity-Driven Dyslipidemia and Fatty Liver Disease

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Obesity is a complex endocrine and metabolic disorder that is related to hyperlipidemia and hepatic insulin resistance. Bile acids (BAs) are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism, their synthesis is mainly controlled via the transcriptional regulation of hepatic farnesoid X receptor in the hepatocytes. On the other hand, FXR also influences lipid metabolism in rodent models of obesity. Polygonum cuspidatum Sieb. Et Zuuc. (Polygonaceae) have been widely used in Chinese folk medicine for the treatment of atherosclerosis, as well as other medical ailments including asthma, hypertension, and cancer. Many chemical components have been reported from this plant, including anthraquinones, stilbenes, flavonoids, and resveratrol. The crude extract of P. cuspidatum has been used in the skin-lightening, antiaging and antiwrinkle cosmetics and for treating burn and scald. In current project, the ethanolic extract of P. cuspidatum has been analyzed by HPLC and the result showed that the concentration of resveratrol in the crude extract of P. cuspidatum was 0.665%. P. cuspidatum has been used as a curative from number of ailments, such as stomach complaints and reduced blood lipid level. Thus, developing protective strategies from P. cuspidatum to minimize the steatotic livers is an urgent need. Male C57B6/J mice which fed high fat diet for 20 weeks obese animals and high-fat diet feeding FXR genetic knockout mice (FXR-/-) models to study the alterations of bile acid pool as well as levels of FXR in liver after P. cuspidatum treatment. Further evaluate the nature and composition of bile acids in blood, and liver. In vitro models, 3T3-L1 adipocyte and AML-12 hepatocyte are used as analyze the cellular mechanisms of bile acid synthesis and dyslipidemia-related factors underlying metabolic disorder in response to P. cuspidatum treatment. The main purpose of the current study will evaluate whether the “P. cuspidatum” affect the SREBP-1, which mediates the gene response to lipid accumulation in obese model and reduces the vulnerability of steatotic livers. The second purpose of this study will evaluate whether the benefits of the “P.cuspidatum” involving in hepatic steatosis could be explained by change in hepatic bile acids signaling pathway. The third aim of this study will test whether the protection by the “P. cuspidatum” against fatty livers is associated with FXR. Expectantly, we will reveal insights on mechanism of fat accumulation accompany dysfunction of bile acidssynthesis and highlight the more benefits of using P. cuspidatum in fatty liver.

Project IDs

Project ID:PC10207-0339
External Project ID:NSC102-2320-B182-014
StatusFinished
Effective start/end date01/08/1331/07/14

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