title: Amplification of palmitate-induced inhibition of cholesterol biosynthesis in cultured rat hepatocytes by garlic-derived organosulfur compounds.
abstract: Incubation of primary cultured rat hepatocytes in the presence of sodium palmitate led to a concentration-dependent inhibition of [(14)C]acetate incorporation into non-saponifiable lipids, particularly cholesterol. This inhibition was enhanced by water-soluble extracts of garlic powder (Kwai®, Sapec®). Comparative studies using different garlic derived organosulfur compounds and related chemicals revealed that the amplification was mainly due to diallyl disulfide (DADS) which was effective at concentrations as low as 5 μM. With the exception of allyl mercaptan which was 10-fold less potent the other compounds tested were ineffective indicating specific structural requirements of this interaction with the palmitate-induced inhibition. Replacement of labeled acetate by labeled mevalonate omitted both inhibition by palmitate and amplification by DADS. Furthermore, palmitate did not influence the DADS-induced changes in the pattern of sterols produced. These results suggest that garlic-derived allylsulfides, especially DADS, interact with the phosphorylation cascade of HMGCoA-reductase which is stimulated by incubation with palmitate presumably via increasing the intracellular level of palmitoyl-CoA. In conclusion, interference with endogeneous regulatory mechanisms may provide an efficent, highly sensitive and physiologically compatible way by which garlic components might influence cholesterol biosynthesis.
authors.affiliation: Physiologisch-chemisches Institut der Universität, D-72076 Tübingen, Hoppe-Seyler-Str. 4.
authors.forename: R
authors.initials: R
authors.lastname: Gebhardt