Comparison of antioxidative capacities and inhibitory effects on cholesterol biosynthesis of quercetin and potential metabolites.
The flavonol quercetin is known to be rapidly metabolized after ingestion by enterocytes and bacteria in the intestinal tract which may influence the biological, e.g. antioxidative potency of this compound. Therefore, quercetin and several of its possible metabolites were compared with regard to their antioxidant activity and their capacity to inhibit hepatocellular cholesterol biosynthesis. Using the 2,2,-diphenylpicrylhydrazyl radical scavenger assay, all compounds with an ortho diphenolic structure acted as strong antioxidants. In contrast, in a cellular assay focusing on lipid peroxidation in cultured rat hepatocytes challenged with tert.-butylhydroperoxide only the lipophilic compounds quercetin and 3,4-dihydroxytoluene were active. Concerning the inhibition of cholesterol biosynthesis, 3,4-dihydroxytoluene surprisingly mimicked the effect of quercetin in primary rat hepatocytes, but much less so in HepG2 cells. All other metabolites were almost ineffective in both cell types. These results suggest that some of the biological functions of flavonoids detectable by in vitro assays may persist in vivo as long as comparably potent metabolites are systemically present.
Glässer
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G
Institut für Biochemie, Medizinische Fakultät, Universität Leipzig, Germany.
Graefe
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EU
Struck
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F
Veit
M
M
Gebhardt
R
R
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology; D002784:Cholesterol / Q000096:biosynthesis*; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008517:Phytotherapy; D010851:Picrates; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000975:Antioxidants; D001713:Biphenyl Compounds; D002396:Catechols; D002839:Chromans; D010851:Picrates; C018599:4-methylcatechol; D012431:Rutin; D002784:Cholesterol; D011794:Quercetin; C004931:1,1-diphenyl-2-picrylhydrazyl; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid