Inhibition of cholesterol biosynthesis by organosulfur compounds derived from garlic |
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Authors: | Lijuan Liu Yu-Yan Yeh |
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Affiliation: | (1) Graduate Program in Nutrition, The Pennsylvania State University, 129 South Henderson Bldg, 16802 University Park, Pennsylvania |
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Abstract: | The study was undertaken to test the inhibitory potential on cholesterogenesis of organosulfur compounds derived from garlic.
The primary rat hepatocytes maintained in Dulbecco's modified Eagle's medium were treated with 2-14C]-acetate as substrate for cholesterol synthesis in the presence or absence of test compounds at 0.05 to 4.0 mmol/L. Eleven
watersoluble and six lipid-soluble compounds of garlic were tested. Among water-soluble compounds,S-allyl cysteine (SAC),S-ethyl cysteine (SEC), andS-propyl cysteine (SPC) inhibited 2-14C]acetate incorporation into cholesterol in a concentration-dependnet manner, achieving 42 to 55% maximal inhibition. γ-Glutamyl-S-allyl cysteine, γ-glutamyl-S-methyl cysteine, and γ-glutamyl-S-propyl cysteine were less potent, exerting only 16 to 29% maximal inhibitions. Alliin,S-allyl-N-acetyl cysteine,S-allylsulfonyl alanine, andS-methyl cysteine had no effect on cholesterol synthesis. Of the lipid-soluble compounds, diallyl disulfide (DADS), diallyl
trisulfide (DATS), and dipropyl disulfide (DPDS) depressed cholesterol synthesis by 10 to 25% at low concentrations (0.5 mmol/L),
and abolished the synthesis at high concentrations (1.0 mmol/L). Diallyl sulfide, dipropyl sulfide, and methyl allyl sulfide
slightly inhibited 2-14C]acetate incorporation into cholesterol only at high concentrations. The complete depression of cholesterol synthesis by
DADS, DATS, and DPDS was associated with cytotoxicity as indicated by marked increase in cellular LDH release. There was no
apparent increase in LDH secretion by water-soluble compounds exceptS-allyl mercaptocysteine, which also abolished cholesterol synthesis. Judging from maximal inhibition and IC50 (concentration required for 50% of maximal inhibition), SAC, SEC, and SPC are equally potent in inhibiting cholesterol synthesis. |
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