Garlic & Health WP 5.2 Cholesterol biosynthesis Frank Struck, Doris Kellert Dr. Sebastian Zellmer, Dr. Gayane Buniatian.

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Presentation transcript:

Garlic & Health WP 5.2 Cholesterol biosynthesis Frank Struck, Doris Kellert Dr. Sebastian Zellmer, Dr. Gayane Buniatian

Organosulphur Compounds Organosulphur compounds of Garlic: Inhibition of cholesterol biosynthesis Potency of Inhibition: Aim:Characterization of the effects on cholesterol biosynthesis Allicin DADS AM 1,3-VDT 1,2-VDT Gebhardt and Beck, Lipids 1996;31:

Organosulphur Compounds Organosulphur compounds of Garlic: Inhibition of cholesterol biosynthesis Indirect Mechanism of Inhibition: Aim:Characterization of the mode of action

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 Solvent 1 2.Pellet Fraction with strong inhibiting effect 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, 1976only trace amounts of quercetin and Michahelles, 1974kaempferol in peeled garlic Kaneta et al., 1980 Leighton et al., 1992 Carotenuto et al., 1996Kaempferol-glycosides in Allium ursinum (no quantitative data) Miean & Mohamed, 2001detailed HPLC analysis, but poorly described plant material Myricetin693 mg/kg dry weight Quercetin 47 Luteolin not detectable Apigenin217

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