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Inhibition of cholesterol biosynthesis in HepG2 cells by artichoke extracts is reinforced by glucosidase pretreatment
Author(s) -
Gebhardt Rolf
Publication year - 2002
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.960
Subject(s) - aglycone , luteolin , biosynthesis , biochemistry , glucoside , enzyme , chemistry , cholesterol , biology , flavonoid , antioxidant , stereochemistry , glycoside , medicine , alternative medicine , pathology
High‐dose aqueous extracts from artichoke leaves were found to inhibit cholesterol biosynthesis from 14 C‐acetate rather moderately in HepG2 cells in contrast to primary cultured rat hepatocytes in which the inhibition was stronger. Preincubation of the extracts with several glycohydrolases revealed that pretreatment with β‐glucosidase considerably reinforced the inhibition. A significant reduction of acetate incorporation was found above extract concentrations of 0.01 mg/mL and at 0.2 mg/mL almost 60% inhibition was observed. Cytotoxic effects detected by the MTT‐assay were restricted to higher concentrations of the extracts with and without β‐glucosidase pretreatment. Since cynaroside represents a major glucoside in artichoke extracts, both cynaroside and its aglycone luteolin were tested. It could be demonstrated that cynaroside is indeed one of the targets of β‐glucosidase and that the liberated luteolin is responsible for the inhibitory effect. Direct measurements of β‐glucosidase activity in rat hepatocytes and HepG2 cells revealed that endogenous enzyme activity in hepatocytes may be sufficient to convert cynaroside to its aglycone, while in HepG2 cells this may not be the case. These findings emphasize the importance of β‐glucosidase‐dependent liberation of luteolin for the ability of artichoke extracts to inhibit hepatic cholesterol biosynthesis. Copyright © 2002 John Wiley & Sons, Ltd.