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Abstract: The relationship between cholesterol and atherosclerosis has gained wide credence and red wine polyphenols have been shown to have an anti-atherogenic activity. In the present in vitro studies, we have evaluated and compared the effects of resveratrol, an active compound of red wine, and of a whole red wine polyphenolic extract (RWE) on the pancreatic bile salt-dependent lipase (BSDL). BSDL is involved in the duodenal hydrolysis of lipid esters and in part of cholesteryl esters thus favoring the bioavailability of free cholesterol. Resveratrol and RWE decrease the human and rat enzyme activities. Resveratrol and RWE also impaired the secretion of BSDL by the rat pancreatic AR4-2J cells used as secreting model. This effect is reversed by the removal of resveratrol or RWE from the cell culture medium. Further, resveratrol (but not RWE) affects the transcription of the gene encoding BSDL and dramatically diminishes the quantity of the enzyme that is expressed and secreted by AR4-2J cells. Results suggest that the hypolipemic effects of red wine polyphenols could partly originate from the inhibition of BSDL activity and secretion in the duodenum. In vivo, these effects could decrease the hydrolysis of dietary lipid esters and likely the absorption of free cholesterol. [Copyright &y& Elsevier]