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Garlic & Health. WP 5.2 Cholesterol biosynthesis. Frank Struck, Doris Kellert. Dr. Sebastian Zellmer, Dr. Gayane Buniatian. 120. 100. 80. Cholesterol Biosynthesis (%). 60. 40. 20. 0. 4. 0,1. 1. 10. 100. 1000. 10. m. Concentration (. M). Organosulphur Compounds.
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Garlic & Health WP 5.2 Cholesterol biosynthesis Frank Struck, Doris Kellert Dr. Sebastian Zellmer, Dr. Gayane Buniatian
120 100 80 Cholesterol Biosynthesis (%) 60 40 20 0 4 0,1 1 10 100 1000 10 m Concentration ( M) Organosulphur Compounds Aim: Characterization of the effects on cholesterol biosynthesis Potency of Inhibition: Organosulphur compounds of Garlic: Inhibition of cholesterol biosynthesis 1,2-VDT 1,3-VDT AM DADS Allicin Gebhardt and Beck, Lipids 1996;31:126-1276
Organosulphur Compounds Aim: Characterization of the mode of action Indirect Mechanism of Inhibition: Organosulphur compounds of Garlic: Inhibition of cholesterol biosynthesis
Garlic Powder: reinvestigation Unexpected Result !! Garlic Powder (Low Quality Garlic): Stimulation of cholesterol biosynthesis !
Garlic Powder: reinvestigation Challenge for present project research: New milestones: - Analysis of responsible compounds - Elucidation of mechanism of action
Garlic Powder: reinvestigation Challenge for present project research: New milestones: - Analysis of responsible compounds - Elucidation of mechanism of action Extraction Procedure
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
Conclusions: • Using a sequential extraction procedure a stimulating fraction and • an inhibiting fraction can be separated from fresh garlic or garlic powder • At least the inhibiting compound is very labile in solution • but stable in dry powder • Garlic contains (two) compounds with opposite effects • on cholesterol biosynthesis Questions: • What is the chemical nature of these compounds? • What are the effects of these compounds on other cellular functions?
Garlic & Health WP 5.2 Garlic flavonoids
Flavonoids in Garlic: Literature Results Starke & Hermann, 1976 only trace amounts of quercetin and Michahelles, 1974 kaempferol in peeled garlic Kaneta et al., 1980 Leighton et al., 1992 Carotenuto et al., 1996 Kaempferol-glycosides in Allium ursinum (no quantitative data) Miean & Mohamed, 2001 detailed HPLC analysis, but poorly described plant material Myricetin 693 mg/kg dry weight Quercetin 47 Luteolin not detectable Apigenin 217
Structure of Favonoids used All tested flavonoids belong to the flavonol group They differ only in the amount and/or position of one or two hydroxyl groups In the case of Luteolin and Kaempferol, several glycosides were also tested
Comparison of the effects of Kaempferol, Luteolin and their glycosides in rat hepatocytes Kaempferol: sensitive stimulation of cholesterol biosynthesis high cytotoxicity (responsible for decline) Luteolin: inhibition of cholesterol biosynthesis (no significant stimulation) low cytotoxicity
Comparison of the effects of Myricetin, Kaempferol and Luteolin in HepG2 cells Myricetin: stimulation of cholesterol biosynthesis Kaempferol: no significant effect Luteolin: inhibition of cholesterol biosynthesis
Flavonoids in Garlic: Hypothesis: Flavonoids of garlic, particularly Kaempferol and Myricetin, may be responsible for the stimulatory effects of garlic powder on cholesterol biosynthesis. Future tasks: • Elucidation of the mode of action of flavonoids like Kaempferol and Myricetin • Detection and quantitation of these flavonoids in garlic powders and other • preparations