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
External Project ID:NSC102-2320-B182-014
Status | Finished |
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Effective start/end date | 01/08/13 → 31/07/14 |
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