Tags

Type your tag names separated by a space and hit enter

Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts.
J Pharmacol Exp Ther. 1998 Sep; 286(3):1122-8.JP

Abstract

High-dose aqueous extracts from artichoke leaves were found to inhibit cholesterol biosynthesis from 14C-acetate in primary cultured rat hepatocytes in a concentration-dependent biphasic manner with moderate inhibition (approximately 20%) between 0.007 and 0.1 mg/ml and more strong inhibition at 1 mg/ml. Cytotoxic effects detected by lactate dehydrogenase leakage and the 3-[4, 5-dimethylthiazol-2-yl]-2,5-dephenyl tetrazolium bromide-assay were restricted to higher concentrations. Replacement of 14C-acetate by 14C-mevalonate largely omitted the inhibiting effect of artichoke extracts indicating an inhibition at the level of hydroxymethylglutaryl-CoA-reductase. However, no direct inhibition of this enzyme could be detected and no other enzymic steps later in the biosynthetic pathway for cholesterol seemed to be affected. Instead, inhibition was found to occur in a time-dependent manner, to last for several hours even after washing out the extracts by fresh medium and to be fully reversible within 20 hr after removal of the extracts. In addition, the stimulation of HMGCoA-reductase activity by insulin was efficiently blocked by the extracts, although other insulin-dependent phenomena, such as increased lactate production, were not influenced. These results suggest an indirect modulation of hydroxymethylglutaryl-CoA-reductase activity as the most likely inhibitory mechanism of the artichoke extracts. Screening of several known constituents of artichoke extracts revealed that cynaroside and particularly its aglycone luteolin were mainly responsible for inhibition, whereas chlorogenic acid was much less effective and caffeic acid, cynarin and other dicaffeoylquinic acids were without significant influence. Indeed, luteolin also efficiently blocked the insulin effect on cholesterol biosynthesis. In conclusion, these results demonstrate that artichoke extracts may inhibit hepatic cholesterol biosynthesis in an indirect but efficient manner and, thus, may contribute via this action to the recently confirmed hypolipidemic influence of this phytopharmacon in man.

Authors+Show Affiliations

Physiologisch-chemisches Institut der Universität, D-72076 Tübingen, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9732368

Citation

Gebhardt, R. "Inhibition of Cholesterol Biosynthesis in Primary Cultured Rat Hepatocytes By Artichoke (Cynara Scolymus L.) Extracts." The Journal of Pharmacology and Experimental Therapeutics, vol. 286, no. 3, 1998, pp. 1122-8.
Gebhardt R. Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts. J Pharmacol Exp Ther. 1998;286(3):1122-8.
Gebhardt, R. (1998). Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts. The Journal of Pharmacology and Experimental Therapeutics, 286(3), 1122-8.
Gebhardt R. Inhibition of Cholesterol Biosynthesis in Primary Cultured Rat Hepatocytes By Artichoke (Cynara Scolymus L.) Extracts. J Pharmacol Exp Ther. 1998;286(3):1122-8. PubMed PMID: 9732368.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts. A1 - Gebhardt,R, PY - 1998/9/11/pubmed PY - 1998/9/11/medline PY - 1998/9/11/entrez SP - 1122 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 286 IS - 3 N2 - High-dose aqueous extracts from artichoke leaves were found to inhibit cholesterol biosynthesis from 14C-acetate in primary cultured rat hepatocytes in a concentration-dependent biphasic manner with moderate inhibition (approximately 20%) between 0.007 and 0.1 mg/ml and more strong inhibition at 1 mg/ml. Cytotoxic effects detected by lactate dehydrogenase leakage and the 3-[4, 5-dimethylthiazol-2-yl]-2,5-dephenyl tetrazolium bromide-assay were restricted to higher concentrations. Replacement of 14C-acetate by 14C-mevalonate largely omitted the inhibiting effect of artichoke extracts indicating an inhibition at the level of hydroxymethylglutaryl-CoA-reductase. However, no direct inhibition of this enzyme could be detected and no other enzymic steps later in the biosynthetic pathway for cholesterol seemed to be affected. Instead, inhibition was found to occur in a time-dependent manner, to last for several hours even after washing out the extracts by fresh medium and to be fully reversible within 20 hr after removal of the extracts. In addition, the stimulation of HMGCoA-reductase activity by insulin was efficiently blocked by the extracts, although other insulin-dependent phenomena, such as increased lactate production, were not influenced. These results suggest an indirect modulation of hydroxymethylglutaryl-CoA-reductase activity as the most likely inhibitory mechanism of the artichoke extracts. Screening of several known constituents of artichoke extracts revealed that cynaroside and particularly its aglycone luteolin were mainly responsible for inhibition, whereas chlorogenic acid was much less effective and caffeic acid, cynarin and other dicaffeoylquinic acids were without significant influence. Indeed, luteolin also efficiently blocked the insulin effect on cholesterol biosynthesis. In conclusion, these results demonstrate that artichoke extracts may inhibit hepatic cholesterol biosynthesis in an indirect but efficient manner and, thus, may contribute via this action to the recently confirmed hypolipidemic influence of this phytopharmacon in man. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9732368/Inhibition_of_cholesterol_biosynthesis_in_primary_cultured_rat_hepatocytes_by_artichoke__Cynara_scolymus_L___extracts_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9732368 DB - PRIME DP - Unbound Medicine ER -