The effects of garlic on lipid metabolism were examined in White Leghorn pullets that had been fed for 4 weeks either a control diet based on corn and soybean meal or an experimental diet containing either 3.8% garlic paste, a solvent extract (petroleum ether, methanol and water in sequence) of garlic paste, the residue or commercial garlic oil. Significant decreases in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (79-83%), cholesterol 7 alpha-hydroxylase (43-51%), fatty acid synthetase (17-29%) and in representative pentose-phosphate pathway (23-39%) activities accompanied the feeding of the petroleum ether-, methanol- and water-soluble fractions of garlic. Garlic paste and oil also suppressed these activities. Significant decreases in serum lipids occurred in response to the feeding of these garlic fractions: serum total cholesterol by 20-25%, low density lipoprotein cholesterol by 28-41% and triglycerides by 10-26%; but high density lipoprotein cholesterol failed to respond to these treatments. The residue remaining after solvent fractionation had little influence on these parameters. These findings were substantiated by a second study in which pullets of a commercial broiler line were fed the garlic fractions. The results confirm that garlic oil and odorous components of garlic lower cholesterol levels. An odorless water-soluble component of garlic also has this effect. The mechanism of the hypocholesterolemic action is at the level of the suppression of cholesterol biosynthesis.

Different concentrations of polar fractions, methanol-soluble (MESF), or water-soluble (WASF), of 1-8% equivalent to fresh garlic paste were added to yellow corn-soybean based diets and fed to 5-week-old male broiler chickens for 3 weeks to measure the inhibition of hepatic beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase (7 alpha-hydroxy) and fatty acid synthetase (FAS). Dose-related decreases in the activities of these enzymes were obtained. Decreases in serum total cholesterol and in low density lipoprotein (LDL) levels were also observed. There was no effect on the level of cholesterol in high density lipoprotein (HDL). The most effective dose for these decreases was found 0.54% (MESF) and 1.2% (WASF) equivalent to 6% of the fresh garlic. The inhibition of HMG-CoA reductase and FAS by 25-300 micrograms of MESF or WASF for 15 min was tested in vitro, in male and female chicken hepatocytes. Inhibitions of activity were dose-dependent and the degree of inhibition increased with duration of incubation (150 micrograms of MESF or WASF 5 to 60 min). Dietary supplementation of odorless WASF of garlic was found to be very effective in lowering the total and LDL cholesterol levels compared to control chickens.

The dissociation of the highly aggregated form of lipopolysaccharide (LPS) from Gram-negative bacteria to the monomeric (or soluble) form is though to be the initial step in the activation of responding cells (macrophages, B-cells, neutrophils, monocytes, and endothelial cells) by LPS. This process is presently not adequately understood. Using the equilibrium dialysis apparatus and a highly purified and well-characterized radiolabeled deep rough chemotype LPS ([14C]ReLPS) from Escherichia coli D31m4, we have examined the effect of pH on its solubility (CT) and ionic states in aqueous media. The solubility range of [14C]ReLPS suspended in 50 mM Tris-HCl-100 mM KCl buffer (or 50 mM MES-100 mM KCl buffer at pH 6.5) was determined to be from (2.91 +/- 0.01) x 10(-8) to (4.55 +/- 0.07) x 10(-8) M over a pH range of 6.50-8.20, respectively. These experimental data satisfactorily fitted the curve generated by the solubility equation CT = S0(1 + K5/[H+])/([H+]/K4' + 1), where S0 is the concentration of the tetraanionic ReLPS, K5 is the dissociation constant of the tetraanionic ReLPS in solution, and K4' is the dissociation constant of the trianionic ReLPS at the surface of the solid particles in suspension. The increase in solubility of ReLPS with increase in pH from 7.00 to 8.20 is primarily caused by the formation of the pentaanionic form from the tetraanions. The pK5 (primarily the second dissociation of the 1-phosphate) of ReLPS was determined to be 8.58 from experimental data.(ABSTRACT TRUNCATED AT 250 WORDS)

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The adaptive increase in avian hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity following fasting and refeeding was muted when the monoterpene d-limonene was fed. The suppression of the induction of HMG-CoA reductase activity was dose dependent to 100 ppm dietary d-Umonene and additive to that of dietary cholesterol. Noninduced hepatic HMG-CoA reductase activity in rats fed a diet containing 1.0% d-limonene was 55% of the activity in rats fed a control diet.Brown and Goldstein (1980) described the multivalent feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in which a non-sterol, post-mevalonate product(s) regulates HMG-CoA reductase

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