Inhibition of cholesterol-biosynthesis in cultured hepatocytes by garlic components

Abstract

Water-soluble extracts of garlic powder inhibit cholesterol-biosynthesis at early and late steps of the pathway. In this study we have tried to identify garlic compounds associated with these different inhibitory actions which are predominant at low and high concentrations, respectively.

Alliin, neither alone nor after incubation with alliinase, was able to inhibit sterol synthesis from ¹⁴C-acetate in cultured rat hepatocytes at the early step. Likewise, allicin caused no reduction, while ajoen diminished sterol synthesis by maximally 16 %. Other compounds containing allyl-and/or sulphur-groups (including y-glutamyl-peptides) did not inhibit, whereas nicotinamide and particularly adenosine caused some inhibition. From all these compounds only allicin and ajoen at high concentrations interacted with the conversion of lanosterol to cholesterol. Both substances led to the accumulation of lanosterol as well as some 7-dehydrocholesterol at the expense of cholesterol. Desmosterol was not accumulating

These results demonstrate that the effects of water-soluble extracts of garlic powder on cholesterol biosynthesis in rat hepatocytes are due to distinct compounds present in garlic which may contribute to the hypocholesterolemic effect of garlic observed in rats and man.

Zusammenfassung

Wäßrige Extrakte von Knoblauchpulver (Kwai^®/Sapec^®) hemmen die Cholesterinbiosynthese in kultivierten Hepatozyten am Anfang des Syntheseweges, hauptsächlich auf der Stufe der Hydroxymethylglutaryl-CoenzymA(HMG-CoA)-Reduktase [3]. Das Maximum dieser Hemmung wird zwischen 0,2 und 8 mg/ml erreicht und beträgt 25 – 30%. In höheren Konzentrationen kann zusätzlich eine Hemmung der Umwandlung der Sterinkörper beobachtet werden, die besonders zur Anhäufung von Lanosterin und in geringerem Maße von 7-Dehydrocholesterin führt [5]. In der vorliegenden Studie wurde der Frage nachgegangen, welche Knoblauchinhaltsstoffe für diese unterschiedlichen Wirkungen verantwortlich sind.