Cholesterol-lowering effect of organosulphur compounds from garlic: a possible mechanism of action.
OBJECTIVE
Hyperlipidemia constitutes a major etiopathological factor for atherosclerosis. The medicinal value of garlic is best known for its lipid lowering effects and antiatherogenic effects. The mechanism by which lipid soluble organosulphur compounds from garlic reduce plasma lipids has not been fully investigated. The author had previously shown that the hepatic activity of beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase, the rate limiting enzyme in cholesterol biosynthesis and the incorporation of radiolabeled (1, 2 14C), acetate into hepatic free and esterified cholesterol was significantly decreased in rat treated with garlic derived organosulphur compounds. We hypothesised that the antiatherogenic effect of the organosulphur compounds may be attributed to the formation of protein internal disulphide and thus inactivation of thiol (-SH) group enzymes such as HMG-CoA reductase and the multienzyme complex of fatty acid synthesis. The objective of the present study is to elucidate the inhibitory mechanism by in vitro studies.


METHODS
Lipid soluble organosulphur compounds from garlic were treated in vitro with Luke's cysteine reagent (representing the thiol (-SH) group of enzymes) and the interaction products were separated by paper chromatography.


RESULTS
The result indicated that the organosulphur compounds were capable of interacting with the thiol (-SH) group of cysteine and thus forming cysteine derivatives.


CONCLUSIONS
The antiatherogenic effects of these organosulphur compounds can be attributed to such reactions that inhibit HMG-CoA reductase and other lipogenic enzymes. The anticarcinogenic effects of these compounds may also be due to inhibitory reactions on enzymes that activate carcinogens.
Mathew
B C
BC
Biochemistry, College of Medical Sciences, Bharatpur, Nepal. bijmathew67@yahoo.co.in
Prasad
N V
NV
Prabodh
R
R
D002784:Cholesterol / Q000096:biosynthesis; D005737:Garlic / Q000737:chemistry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000188:drug therapy; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000627:therapeutic use
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013438:Sulfhydryl Compounds; D002784:Cholesterol