Document Detail

Comparison of synthetic saponin cholesterol absorption inhibitors in rabbits: evidence for a non-stoichiometric, intestinal mechanism of action.
MedLine Citation:
PMID:  10064735     Owner:  NLM     Status:  MEDLINE    
The hypocholesterolemic activities of pamaqueside and tiqueside, two structurally similar saponins, were evaluated in cholesterol-fed rabbits. The pharmacological profiles of the saponins were virtually identical: both dose-dependently decreased the intestinal absorption of labeled cholesterol 25-75%, increased fecal neutral sterol excretion up to 2.5-fold, and decreased hepatic cholesterol content 10-55%. High doses of pamaqueside (>5 mg/kg) or tiqueside (>125 mg/kg) completely prevented hypercholesterolemia. Decreases in plasma and hepatic cholesterol levels were strongly correlated with increased neutral sterol excretion. Ratios of neutral sterol excreted to pamaqueside administered were greater than 1:1 at all doses, in opposition to the formation of a stoichiometric complex previously suggested for tiqueside and other saponins. Ratios in tiqueside-treated rabbits were less than unity, a reflection of its lower potency. Pamaqueside-treated rabbits exhibited a more rapid decline in plasma cholesterol concentrations than control animals fed a cholesterol-free diet, indicating that the compound also inhibited the absorption of biliary cholesterol. Intravenous administration of pamaqueside had no effect on plasma cholesterol levels despite plasma levels twice those observed in rabbits given pamaqueside orally. These data indicate that pamaqueside and tiqueside induce hypocholesterolemia by blocking lumenal cholesterol absorption via a mechanism that apparently differs from the stoichiometric complexation of cholesterol hypothesized for other saponins.
L A Morehouse; F W Bangerter; M P DeNinno; P B Inskeep; P A McCarthy; J L Pettini; Y E Savoy; E D Sugarman; R W Wilkins; T C Wilson; H A Woody; L M Zaccaro; C E Chandler
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of lipid research     Volume:  40     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-13     Completed Date:  1999-04-13     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  464-74     Citation Subset:  IM    
Department of Cardiovascular and Metabolic Diseases, Pfizer Central Research, Eastern Point Road, Groton, CT 06340, USA.
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MeSH Terms
Administration, Oral
Anticholesteremic Agents / pharmacology
Bile / metabolism
Cholesterol / blood
Cholesterol, Dietary / metabolism*
Cholesterol, HDL / blood
Feces / chemistry
Hypercholesterolemia / metabolism
Injections, Intravenous
Intestinal Absorption / drug effects*
Liver / metabolism
Molecular Structure
Saponins / pharmacology*
Sterols / analysis
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Cholesterol, Dietary; 0/Cholesterol, HDL; 0/Saponins; 0/Sterols; 0/pamaqueside; 57-88-5/Cholesterol; 99759-19-0/tiqueside

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