Inhibitory Effects of Triterpenes and Flavonoids on the Enzymatic Activity of Hyaluronic Acid‐Splitting Enzymes

Abstract

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.

Honey shows potent inhibitory activity against the bovine testes hyaluronidase

“…In agreement with our study, previous in vitro research reported that 30 different flavonoid components exhibited inhibition against BTHase, and that inhibition levels were determined, from highest to lowest, in silibinin4kaempferol4apigenin4luteolin4tan-nin 33 . The idea that flavonoids possess anti-hyaluronidase activity has also been supported by other studies 4,8,12,34 .…”

Cyclic Spermidine Alkaloids and Flavone Glycosides from Meehania fargesii

“…17,31) Lithospermic acid B is a phenylpropanoid tetramer with inhibitory activity comparable to that of the oligomers. Some flavonoids have been reported to inhibit of hyaluronidase, 32,33) and diosmetin-7-O-b-D-glucuronide and apigenin-7-O-b-Dglucuronide were also revealed as active compounds. Previously, in phytochemical studies of the Meehania genus, we found 23 spermidine alkaloidal glycosides in M. urticifolia.…”

Hyaluronidase Inhibitors: A Biological and Therapeutic Perspective

“…Further, glycyrrhizin and glycyrhetinic acid showed maximum inhibition towards Hyal B (Streptococcus agalactiae) and rHyal B (recombinant S. agalactiae), whereas, the weak inhibition was observed for HAase from the bovine testis, Hyal S (Streptomyces hyalurolyticus), and Hyal C (S. equisimilis). A noncompetitive dead end inhibition was observed for glycyrrhizin on rHyal B [145]. In the same study, the authors selected different flavonoids depending on their number of hydroxyl groups and side chain substituents.…”