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1.
Chem Biol Interact ; 272: 153-159, 2017 Jun 25.
Article in English | MEDLINE | ID: mdl-28549616

ABSTRACT

Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT.


Subject(s)
Bile Acids and Salts/metabolism , Cholesterol/blood , Gene Expression/drug effects , Oligosaccharides/pharmacology , Pectins/pharmacology , ATP Binding Cassette Transporter 1/genetics , ATP Binding Cassette Transporter 1/metabolism , ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism , Animals , Apolipoprotein A-I/blood , Cholesterol 7-alpha-Hydroxylase/genetics , Cholesterol 7-alpha-Hydroxylase/metabolism , Cholesterol, HDL/blood , Diet, High-Fat , Intestine, Small/drug effects , Intestine, Small/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice , Pectins/chemistry , Scavenger Receptors, Class B/genetics , Scavenger Receptors, Class B/metabolism , Steroid 12-alpha-Hydroxylase/genetics , Steroid 12-alpha-Hydroxylase/metabolism
2.
Chem Biol Interact ; 238: 42-7, 2015 Aug 05.
Article in English | MEDLINE | ID: mdl-26070415

ABSTRACT

This study aims to compare the effects of feeding haw pectin (HP), haw pectin hydrolyzates (HPH), and haw pectin pentasaccharide (HPPS) on the cholesterol metabolism of hypercholesterolemic hamsters induced by high-cholesterol diets. The animals were fed a standard diet (SD), high-cholesterol diet (HCD), or HCD plus HP, HPH, or HPPS at a dose of 300mg/kg body weight for 4weeks. Results showed that HPPS was more effective than HP and HPH in decreasing the body weight gain (by 38.2%), liver weight (by 16.4%), and plasma and hepatic total cholesterol (TC; by 23.6% and 27.3%, respectively) of hamsters. In addition, the bile acid levels in the feces were significantly higher by 39.8% and 132.8% in the HPH and HPPS groups than in the HCD group. Such changes were not noted in the HP group. However, the HP group had higher cholesterol excretion capacities than the HPH and HPPS groups by inhibiting cholesterol absorption in the diet, with a 21.7% increase in TC excretion and a 31.1% decrease in TC absorption. Thus, HPPS could be a promising anti-atherogenic dietary ingredient for the development of functional food to improve cholesterol metabolism.


Subject(s)
Cholesterol/metabolism , Crataegus/metabolism , Diet, High-Fat , Liver/drug effects , Pectins/pharmacology , Plant Extracts/pharmacology , Animals , Bile Acids and Salts/analysis , Cholesterol/blood , Cholesterol, HDL/analysis , Cholesterol, HDL/blood , Chromatography, High Pressure Liquid , Crataegus/chemistry , Cricetinae , Feces/chemistry , Lipids/analysis , Liver/metabolism , Liver/pathology , Male , Pectins/metabolism , Plant Extracts/metabolism , Triglycerides/analysis , Triglycerides/blood
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