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Arch Pharm (Weinheim) ; 339(6): 313-8, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16718670

RESUMEN

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.


Asunto(s)
Flavonoides/farmacología , Ácido Glicirretínico/farmacología , Ácido Glicirrínico/farmacología , Hialuronoglucosaminidasa/antagonistas & inhibidores , Polisacárido Liasas/antagonistas & inhibidores , Animales , Sitios de Unión , Bovinos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Flavonoides/química , Ácido Glicirretínico/química , Ácido Glicirrínico/química , Ácido Hialurónico/metabolismo , Hialuronoglucosaminidasa/metabolismo , Técnicas In Vitro , Cinética , Masculino , Estructura Molecular , Polisacárido Liasas/genética , Polisacárido Liasas/metabolismo , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/metabolismo , Streptococcus agalactiae/enzimología , Relación Estructura-Actividad , Especificidad por Sustrato , Testículo/enzimología
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