ABSTRACT
Flavonoid glycosides were metabolized to phenolic acids via aglycones by human intestinal microflora producing alpha-rhamnosidase, exo-beta-glucosidase, endo-beta-glucosidase and/or beta-glucuronidase. Rutin, hesperidin, naringin and poncirin were transformed to their aglycones by the bacteria producing alpha-rhamnosidase and beta-glucosidase or endo-beta-glucosidase, and baicalin, puerarin and daidzin were transformed to their aglycones by the bacteria producing beta-glucuronidase, C-glycosidase and beta-glycosidase, respectively. Anti-platelet activity and cytotoxicity of the metabolites of flavonoid glycosides by human intestinal bacteria were more effective than those of the parental compounds. 3,4-Dihydroxyphenylacetic acid and 4-hydroxyl-phenylacetic acid were more effective than rutin and quercetin on anti-platelet aggregation activity. 2,4,6-Trihydroxybenzaldehyde, quercetin and ponciretin were more effective than rutin and ponciretin on the cytotoxicity for tumor cell lines. We insist that these flavonoid glycosides should be natural prodrugs.
Subject(s)
Bacteria/metabolism , Flavonoids/metabolism , Flavonoids/pharmacology , Intestines/microbiology , Biotransformation , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Flavonoids/toxicity , Glycosides/metabolism , Humans , Phenols/metabolism , Phenols/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Trypsin Inhibitors/pharmacology , Tumor Cells, CulturedABSTRACT
A beta-glucosidase (EC 3.2.1.21.) was purified 2500-fold from Bacteroides JY-6, an intestinal anaerobic bacterium of human. The specific activity of the homogeneously purified enzyme was 210 mumol/min/mg protein. The enzyme (M(r) 75kDa) was an monomer whose pI and optimal pH values were 4.6 and 5.5-6, respectively. The best substrates were p-nitrophenyl beta-D-glucopyranoside and natural beta-bound glucosides, such as prunin and poncirenin. Puerarin, which is a C-glycoside, was weakly effective. However, cellobiose, alpha-bound glycosides and rhamnoglucosides were not effective. The apparent Kms for prunin and p-nitrophenyl-beta-D-glucopyranoside were determined to be 0.08 and 0.19 mM, respectively. The enzyme was strongly inhibited by p-chloromercuriphenylsulfonic acid and reaction products such as p-nitrophenol and glucose.
Subject(s)
Bacteroides/enzymology , Intestines/microbiology , beta-Glucosidase/analysis , Bacterial Proteins/analysis , Electrophoresis, Polyacrylamide Gel , Feces/microbiology , Humans , Hydrogen-Ion Concentration , Kinetics , Molecular Weight , Spectrophotometry, Ultraviolet , Substrate Specificity , beta-Glucosidase/isolation & purification , beta-Glucosidase/metabolismABSTRACT
Arylsulfate sulfotransferase purified from Eubacterium A-44 has higher specific activity than the enzymes from Klebsiella K-36 and Haemophilus K-12. Propylparaben and butylparaben were good substrates among several parabens. The antibacterial activity of parabens was reduced by the sulfation of the phenolic hydroxy group. Tyrosine-containing peptides, kyotorphin, enkephalin and cholecystokinin non-sulfate, were effective as acceptor substrates by A-44, K-36 and K-12 sulfotransferases.
