Effects on lipid levels and lipid metabolism under more human-like conditions. –Lipid levels,...
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• Effects on lipid levels and lipid metabolism under more human-like conditions. – Lipid levels, cholesterol synthesis and cholesterol absorption. • Effects on fast atherosclerosis development and other processes that might be related with atherosclerosis. – Inflammation, blood pressure, platelet activation and atherosclerosis analysis. Aim of the study: Effects of Aim of the study: Effects of garlic on lipid metabolism and garlic on lipid metabolism and atherosclerosis atherosclerosis
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Transcript of Effects on lipid levels and lipid metabolism under more human-like conditions. –Lipid levels,...
• Effects on lipid levels and lipid metabolism under more human-like conditions. – Lipid levels, cholesterol synthesis and cholesterol
absorption.
• Effects on fast atherosclerosis development and other processes that might be related with atherosclerosis.– Inflammation, blood pressure, platelet activation and
atherosclerosis analysis.
Aim of the study: Effects of garlic on lipid Aim of the study: Effects of garlic on lipid metabolism and atherosclerosismetabolism and atherosclerosis
APOE*3-Leiden transgenic mouse as a model for hyperlipidemia and
atherosclerosis studies
• Transgenic mice carrying a mutant form of human APOE*3 gene.
• Dominant dysfunctional APOE*3-Leiden results in defect in chylomicron/ VLDL clearance and more human-like lipoprotein profile.
• Highly responsive to feeding cholesterol-rich diets.
• Develops atherosclerosis varying from fatty streaks to more human-like complicated lesions.
Effect of garlic on lipid metabolism and Effect of garlic on lipid metabolism and atherosclerosis in APOE*3-Leiden mice: atherosclerosis in APOE*3-Leiden mice:
Selection of compoundsSelection of compounds
• Lichtwer LI111 garlic powder: Reference dry garlic powder.
• Morado de Cuenca 200 (Mor200): Garlic powder rich in organic sulfur-containing compounds.
• Diallyl disulfide (DADS): Isolated garlic compound rich in sulfur.
• Allicin: Reference isolated garlic compound reported to result in 43% reduction of fatty streaks in C57Black/6 mice
(D. Abramovitz et al., Coronary Artery Disease, 1999, 10: 515-519)
Effect of garlic on lipid metabolism and Effect of garlic on lipid metabolism and atherosclerosis in APOE*3-Leiden mice: atherosclerosis in APOE*3-Leiden mice:
Experimental scheme
Effect of garlic on lipid metabolism and Effect of garlic on lipid metabolism and atherosclerosis in APOE*3-Leiden mice: atherosclerosis in APOE*3-Leiden mice:
Experimental scheme-2
Matching and start of the studyWeight and food intakeBlood sampling/ plasma isolationPlasma lipid levels Cholesterol lipoprotein profile Chol. synthesis/ Intestinal absorption
Platelet activation measurements
Marker for liver function Liver lipid composition
Atherosclerotic aorta lesions area
Inflammation markers
2 4
6
8 10 12
14
80
8080
80
pp
60
p60
60
80
80
80
pp
6565
65
pp p
80 65
p p p p
8065
65
65
65
6065
65
16
Regular diet Western diet Atherogenic diet
60
p
Blood pressure
Compound biostability
65
p p
80
p
5
65
p
15
Run in
18 20 22
65
25
p
65
65
65
80 65
p
65
0
Atherosclerotic aorta lesions typing 605
General parameters Inflammation and atherosclerosis related parameters
Lipid metabolism related parameters
80
Effect of garlic on plasma cholesterol levels under 3 dietary conditions
*P< 0.05
Plasma cholesterol levels
Regular diet Western diet Atherogenic diet
mM
Control 3.1 9.3 63
LI111 2.9 9.3 57
Mor 200 3.0 9.1 44 *
DADS 2.9 8.3 70
Allicin 3.5 * 9.2 73
Effect of garlic on markers of cholesterol synthesis and intestinal absorption under
3 dietary conditions Regular diet
*P< 0.05
0.0
0.5
1.0
1.5
Control LI111 Mor 200 DADS Allicin
0
10
20
30
40
Control LI111 Mor 200 DADS Allicin
campesterolb-sitosterol
Con
cen
trat
ion
(µ
mol
ste
rol /
mm
ol c
hol
este
rol)
squalenelathosterollanosterol
Markers of cholesterol synthesis
Markers of intestinal absorption
Effect of garlic on liver function under 3 dietary conditions
tP=0.051
Regular diet Western diet Atherogenic diet
Control 33.4 30.3 175
LI111 33.2 34.4 104
Mor 200 32.9 30.3 94.1
DADS 29.9 41.8 203
Allicin 25.2 28.2 171
Plasma alanine amino transferase
t
t
U/L
Effect of garlic on Serum Amyloid A and von Willebrand factor concentrations
under fast atherogenic conditions
SA
A (
µg
/ m
l)
Control LI111 Mor 200 DADS Allicin
0
50
100
150
200
250
vWF
(%
PP
)
Control LI111 Mor 200 DADS Allicin
0
2
4
6
8
**
p=0.001
p<0.001
*P< 0.05
• Control
• Primador FRANCE 2001: 0.64 g/kg b.w. of dry garlic powder with low sulphur content.
• Primador FRANCE 2001: 6.4 g/kg b.w. of dry garlic powder with high sulphur content.
• Kyolic (positive control): 200 mg/kg b.w. of powder rich in S-allylcysteine reported to result in 64% reduction of fatty streaks in New Zealand white rabbits.
Campbell JH, Efendy JL, et al. J.Nutrition. 2001;131:1006S-1009S.
Effect of garlic powders on atherosclerosis under more human-like
conditions: Groups selection
Effect of garlic powders on atherosclerosis under more human-like conditions:
Experimental design
Matching and start of the studyWeight and food intakeBlood sampling/ plasma isolationPlasma lipid levels Cholesterol lipoprotein profile
vWf, t-PA and soluble ICAM
Marker for liver function
Liver lipid composition (p.m.)
Aortic root lesions composition
Aortic root lesions typing and area
8 12
60
6060
60
55
55
55
60
60
606060
60
p
55
Diet T + 0.2% cholesterol
55
p
SAA and Fibrinogen
Compound biostability
60
p
5
Run in26
28
60
0
Aortic arch area and lipids deposition 555
General parameters Inflammation and atherosclerosis developmentrelated parameters
Lipid metabolism related parameters
In weeks
5
5
4
60
60
60
16
6060
60
20
6060
60
60
60
24
6060
60
p
55
55All blood stimulation assay 55
p pp p p p p
p
p
Mice on standard chow diet 8
