garlic & health:health part - general aim main goal:- interactive improvement of garlic quality...
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Garlic & Health: Health part - general aim
Main Goal: - Interactive improvement of garlic quality
Elucidation of mechanismAnalysis of active of actioncompounds Improved drug
formulationHigh quality garlic
Improvement of garlic Optimal use of garlicplants and growth conditions for therapeutic application
Main Focus: - 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
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 andsignal transduction pathways
Production of matrix metalloproteinases and inhibitors (TIMP) byendothelial cells under the influence of organosulphur compounds.
Inhibition of Matrix-Metallo-proteinases by Garlic
Compounds K. Meyer and R. Gebhardt
Institute of Biochemistry
University of Leipzig
MMP
MMP
MMP
TIMP
TIMP
TIMP
Arteriosclerosis FibrosisArthritis Diabetic Nephro-Rheumatoid Arthritis pathyInflammationGlomerulosclerosisTumour-Growth Scleroderma -Metastasis -AngiogenesisUlcersParodontosis
Morphogenesis, Differentiation, Wound healing, etc.
Pathological Implicationsof MMP-TIMP-Imbalance:
Spectrum of matrix metalloproteinasesand 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 metalloproteinasesand 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 ELISA
MMP-1 and MMP-3 are not affected by DADS,AM and SAC in HUVEC cells
Inhibition of MMP-9 and TIMP-1 Production by DADS, AM and SAC
MMP-9 (activity assay) TIMP-1 (ELISA)
- Unstimulated HUVEC cells do not secrete MMP-9
- In the case of TIMP-1 unstimulated cells respond similarly
HUVEC stimulated with PMA, forskolin and TNF-alpha
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
(HUVEC stimulated with TNF-alpha, forskolin and PMA, 24 h)
TIMP-1 ELISA Cytotoxicity (MTT)
MMP-9 Activity Assay
No response of HUVEC to the garlic extractMOR-200 below cytotoxic concentrations
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