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Garlic & Health: Health part - general aim

Garlic & Health: Health part - general aim. Main Goal: - Interactive improvement of garlic quality Elucidation of mechanism Analysis of active of action compounds Improved drug formulation High quality garlic Improvement of garlic Optimal use of garlic

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Garlic & Health: Health part - general aim

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  1. Garlic & Health: Health part - general aim Main Goal: - Interactive improvement of garlic quality Elucidation of mechanism Analysis of active of action compounds Improved drug formulation High quality garlic Improvement of garlicOptimal use of garlic plants and growth conditions for therapeutic application Main Focus:- Inflammation and cytokine signaling - Atherosclerosis and serum cholesterol - Cancer and biotransformation - Human Intervention Study

  2. 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

  3. 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

  4. Garlic & Health WP 5.2 Cholesterol and vessel wall

  5. 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.

  6. Mechanisms of Arteriosclerosis Serum Cholesterol MMPs + TIMPs

  7. Inhibition of Matrix-Metallo-proteinases by Garlic Compounds K. Meyer and R. Gebhardt Institute of Biochemistry University of Leipzig

  8. Pathological Implicationsof MMP-TIMP-Imbalance: MMP TIMP Morphogenesis, Differentiation, Wound healing, etc. TIMP MMP TIMP MMP Arteriosclerosis Fibrosis Arthritis Diabetic Nephro- Rheumatoid Arthritis pathy Inflammation Glomerulosclerosis Tumour-Growth Scleroderma -Metastasis -Angiogenesis Ulcers Parodontosis

  9. 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

  10. 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

  11. 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

  12. 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) TIMP-1 (ELISA) - Unstimulated HUVEC cells do not secrete MMP-9 - In the case of TIMP-1 unstimulated cells respond similarly

  13. Inhibition of MMP-1 Production in HCAEC by DADS, AM and SAC (HCAEC stimulated with TNF-alpha, forskolin and PMA) (HCAEC unstimulated)

  14. Inhibition of TIMP-1 Production in HCAEC by DADS, AM and SAC (HCAEC stimulated with TNF-alpha, forskolin and PMA) (HCAEC unstimulated)

  15. Influence of MOR-200 on MMP-9 and TIMP-1 Production by HUVEC cells (HUVEC stimulated with TNF-alpha, forskolin and PMA, 24 h) MMP-9 Activity Assay No response of HUVEC to the garlic extract MOR-200 below cytotoxic concentrations TIMP-1 ELISA Cytotoxicity (MTT)

  16. 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

  17. 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

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