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Inhibition of cholesterol biosynthesis by organosulfur compounds derived from garlic

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Lipids

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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Abbreviations

ANOV:

analysis of variance

DADS:

diallyl disulfide

DAS:

diallyl sulfide

DATS:

diallyl trisulfide

DMEM:

Dulbecco's modified Eagle's medium

DMSO:

dimethyl sulfoxide

DPDS:

dipropyl disulfide

DPS:

dipropyl sulfide

FBS:

fetal bovine serum

GSAC:

γ-glutamyl-S-allyl cysteine

GSMC:

γ-glutamyl-S-methyl cysteine

GSPC:

γ-glutamyl-S-propyl cysteine

IC50 :

concentration required for 50% of maximal inhibition

LDH:

lactate dehydrogenase

MAS:

methyl allyl sulfide

NMOR:

N-nitrosomorpholine

SAC:

S-allyl cysteine

SAMC:

S-allyl mercaptocysteine

SANC:

S-allyl-N-acetyl cysteine

SASA:

S-allylsulfonyl alanine

SEC:

S-ethyl cysteine

SMC:

S-methyl cysteine

SPC:

S-propyl cysteine

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Correspondence to Yu-Yan Yeh.

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Liu, L., Yeh, YY. Inhibition of cholesterol biosynthesis by organosulfur compounds derived from garlic. Lipids 35, 197–203 (2000). https://doi.org/10.1007/BF02664770

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  • DOI: https://doi.org/10.1007/BF02664770

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