Garlic & Health:
Main Goal:
Health part - general aim
- Interactive improvement of garlic quality
Elucidation of mechanism
Analysis of active
compounds
of action
Improved drug
formulation
High quality garlic
Improvement of garlic
plants and growth conditions
Main Focus:
Optimal use of garlic
for therapeutic application
- Inflammation and cytokine signaling
- Atherosclerosis and serum cholesterol
- Cancer and biotransformation
- Human Intervention Study
Garlic & Health:
Health part
Major achievements:
•
new findings on bioavailability,
identification of new metabolites
•
definition/exclusion of biomolecular mechanisms
mainly of single compounds,
but also on extracts by using in vitro systems
•
establishment of a reliable analytics of
organosulphur compounds
•
first evaluation of efficacy of single molecules
and extracts in an animal study
Garlic & Health:
Health part
Future focus:
•
continuation of the work of each workpackage
•
integration of our new results
•
efficient and extensive in vivo evaluation
• intensification of dissemination of data
and major achievements
Garlic & Health
WP 5.2
Cholesterol and vessel wall
WP 5.2
Cholesterol and vessel wall
Milestones:
Characterization of the interaction of organosulphur compounds
(DADS and AM) with cholesterol metabolism
Studies on garlic with different sulphur fertilization
Interactions of garlic flavonoids with cholesterol biosynthesis and
signal transduction pathways
Production of matrix metalloproteinases and inhibitors (TIMP) by
endothelial cells under the influence of organosulphur compounds.
Mechanisms of Arteriosclerosis
Serum
Cholesterol
MMPs +
TIMPs
Inhibition of Matrix-Metalloproteinases by Garlic Compounds
K. Meyer and R. Gebhardt
Institute of Biochemistry
University of Leipzig
Pathological Implications
of MMP-TIMP-Imbalance:
MMP
TIMP
Morphogenesis, Differentiation, Wound healing, etc.
TIMP
MMP
Arteriosclerosis
Arthritis
Rheumatoid Arthritis
Inflammation
Tumour-Growth
-Metastasis
-Angiogenesis
Ulcers
Parodontosis
MMP
TIMP
Fibrosis
Diabetic Nephropathy
Glomerulosclerosis
Scleroderma
Spectrum of matrix metalloproteinases
and TIMP-1 in cultured HUVEC cells.
After 9 h of cultivation.
Induction of MMPs and TIMP-1
in HUVEC cells
9 / 24 h after PMA, forskolin and TNF-alpha
Spectrum of matrix metalloproteinases
and TIMP-1 in cultured HCAEC cells.
After 9 h of cultivation.
Induction of MMPs and TIMP-1
in HCAEC cells
9 h after PMA, forskolin and TNF-alpha
Inhibition of MMP-2 Production in HUVEC by DADS, AM and SAC
Activity assay
MMP-1 and MMP-3 are not affected by DADS,
AM and SAC in HUVEC cells
ELISA
Inhibition of MMP-9 and TIMP-1 Production by DADS, AM and SAC
HUVEC stimulated with PMA, forskolin and TNF-alpha
MMP-9 (activity assay)
- Unstimulated HUVEC cells do not secrete MMP-9
- In the case of TIMP-1 unstimulated cells respond
similarly
TIMP-1 (ELISA)
Inhibition of MMP-1 Production in HCAEC by DADS, AM and SAC
(HCAEC stimulated with
TNF-alpha, forskolin and PMA)
(HCAEC unstimulated)
Inhibition of TIMP-1 Production in HCAEC by DADS, AM and SAC
(HCAEC stimulated with
TNF-alpha, forskolin and PMA)
(HCAEC unstimulated)
Influence of MOR-200 on MMP-9 and TIMP-1 Production by HUVEC cells
MMP-9 Activity Assay
(HUVEC stimulated with
TNF-alpha, forskolin and PMA, 24 h)
No response of HUVEC to the garlic extract
MOR-200 below cytotoxic concentrations
TIMP-1 ELISA
Cytotoxicity (MTT)
Inhibition of MMP-2 Production by different garlic extracts
(MOR-200; MES-200; PRI-200; PRI-0)
(unstimulated HCAEC cells)
RESULTS:
- Inhibtion is stronger in
HCAEC than in HUVEC cells
- only slight differences between
garlic extracts with different
fertilization
Summary:
• DADS is able to inhibit the production of several MMPs
and of TIMP-1 by endothelial cells
• HCAEC cells are more sensitive to DADS than HUVEC cells
• AM and SAC are less potent than DADS
• Garlic powders do not affect HUVEC cells
but exert an inhibition of MMP production in HCAEC cells
• so far no significant influence of garlic fertilization
Final conclusion:
• Garlic preparations may potentially influence the
MMP-TIMP balance in certain endothelia