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Main Topics of Research in the Health Part

Main Topics of Research in the Health Part. Effects of garlic powders and known compounds on cellular functions related to arteriosclerosis or inflammation Univ. Munich / Univ. Leipzig / TNO The Netherlands Bioavailability and metabolic fate of garlic compounds

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Main Topics of Research in the Health Part

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  1. Main Topics of Research in the Health Part • Effects of garlic powders and known compounds on cellular • functions related to arteriosclerosis or inflammation • Univ. Munich / Univ. Leipzig / TNO The Netherlands • Bioavailability and metabolic fate of garlic compounds • INRA Dijon / Lichtwer Berlin • Search for new effectors in garlic powder • Univ. Leipzig

  2. Activation of the transcription factor NF-kB (Univ. Munich / measured by a new expression assay) • Garlic constituents showed no inhibition of TNF induced NF-B activation. • Only Printanor 0 solved in Media was able to inhibit TNF induced NF-B activation. Results:

  3. Effects of garlic extracts or compounds on liberation of cytokines from human blood cells • Garlic extracts are able to reduce LPS induced liberation of the pro-inflammatory cytokines Il-1 and TNF. • Garlic extracts are able to increase the LPS induced liberation of anti-inflammatory cytokine Il-10. • It is noticeable that unfertilised garlic is less active than fertilised garlic. • The liberation of cytokines through RPMI garlic extracts is most likely mediated by endotoxin contaminations.

  4. Il-1 

  5. Inhibition of MMP-Production by garlic compounds (Univ. Leipzig / Coronary artery and umbilical vein endothelial cells) MMP-2 by HCAEC cells

  6. Conclusions: • DADS is able to inhibit the production of several MMPs • particularly in HCAEC cells • AM is less potent than DADS • Garlic powder (PRI-200, MOR-200) has a similar effect • Garlic powder (PRI-0) is less effective • Garlic preparations might influence the MMP-TIMP balance Questions: • What is the effect of garlic material on the production of TIMPs ?

  7. Effect of garlic material on plasma lipids in transgenic mice (TNO the Netherlands / additions to different diets) • Garlic powder (Li111) and DADS significantly lowered food intake and body weight gain • Neither garlic powders (Li; MOR200) nor DADS or Allicin significantly changed serum cholesterol and TGL levels, blood pressure or platelet activation. Results:

  8. Metabolism in vitro of DADS (INRA Dijon / rat liver microomes, cytosol) O S O AMSO2 , Allylmethylsulfone O S S S DADS, diallyldisulfide AMSO, allyl methyl sulfoxide S Allyl methyl sulfur SH AM, Allyl mercaptan O S S S-glutathion S DADSO, allicin AGS, Allylglutathionylsulfure

  9. DADS:short half life time many metabolites  Which is the real active molecule in vivo ?

  10. Metabolites in plasma 1- Early 2- long time -Very low levels of AM and AMS - Rapid appearance of AMSO and AMSO2(10 min.) - Peaks at the second day

  11. Comparison of commercial garlic preparations and dissolution studies (Lichtwer Berlin / HPLC analysis) • There are considerable differences in alliin and g-glutamylpeptides in garlic preparations. • Dissolution around pH 8 results in rapid conversion of alliin, but only 60-70% is found as allicin. G-glutamylpeptides dissolve rapidly and remain essentially stable for 2 h. Results:

  12. Modulation of Cholesterol Biosynthesis by Garlic Compounds Sulfate fertilization Stim Inhib Univ. of Leipzig / in vitro study in hepatocytes 0 100 200

  13. Stimulation and inhibition of cholesterol biosynthesis in Hepatocytes and HepG2 Cells by garlic powder extracted subsequently with different solvents

  14. Separation scheme for garlic compounds with different effects on hepatic cholesterol biosynthesis: Garlic or Garlic Powder Solvent 2 /evapuration / reuptake Solvent 1 Fraction with very strong stimulating effect 1.Pellet Fraction with strong inhibiting effect Solvent 1 2.Pellet Needs to be kept under nitrogen

  15. Conclusions: • Garlic contains (two) compounds with opposite effects on cholesterol biosynthesis Questions: • What is the chemical nature of the responsible compounds? • Are tthese compounds effective in vivo? • Do these compounds have effects on other cellular functions • than cholesterol biosynthesis?

  16. MT CYP 2B1/2 CYP 2E1 FMO Compounds obtained in presence of subcellular fractions Compounds obtained in an isolated perfused liver AMSO2 allyl methyl sulfone AMSO allyl methyl sulfoxide AMS allyl methyl sulfide DADS AM allyl mercaptan GST AGS allyl glutathionyl sulfide DADSO

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