Inhibitory effects of triterpenes and flavonoids on the enzymatic activity of hyaluronic acid-splitting enzymes.
The effect of triterpenes and flavonoids on the activity of several hyaluronic acid-splitting enzymes was investigated. Studies showed that the inhibitory effect of the triterpenes glycyrrhizin and glycyrrhetinic acid is dependent on the source of hyaluronate lyase. Hyaluronate lyase from Streptococcus agalactiae (Hyal B) and recombinant hyaluronate lyase from Streptococcus agalactiae (rHyal B) demonstrated strongest inhibition. In contrast, hyaluronate lyases from Streptomyces hyalurolyticus (Hyal S), Streptococcus equisimilis (Hyal C) and hyaluronidase from bovine testis (Dase) showed only reduced inhibition action. A non-competitive dead end inhibition with Ki=3.1+/-1.8x10(-6) mol/mL and Kii=6.7+/-2.4x10(-6) mol/mL was found for glycyrrhizin on recombinant hyaluronate lyase from Streptococcus agalactiae. The inhibitory effect of flavonoids on Hyal B, rHyal B and Dase was determined depending on the number of hydroxyl groups and side chain substituents in the molecule. Flavonoids with many hydroxyl groups inhibited hyaluronate lyase stronger than those with only a few. Native hyaluronate lyase (Hyal B) showed a more extensive inhibition than the recombinant protein (rHyal B). Accordingly, the inhibition by triterpenes and flavonoids is presumably specific for each hyaluronic acid (HA)-splitting enzyme.
Hertel
Waltraud
W
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Peschel
Gundela
G
Ozegowski
Jörg-Hermann
JH
Müller
Peter-Jürgen
PJ
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000737:chemistry / Q000494:pharmacology*; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000378:metabolism; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D015394:Molecular Structure; D011133:Polysaccharide-Lyases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013292:Streptococcus agalactiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D011994:Recombinant Proteins; D019695:Glycyrrhizic Acid; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; D011133:Polysaccharide-Lyases; C100002:hyaluronate lyase; D006034:Glycyrrhetinic Acid