Taxifolin inhibits rat and human 11β-hydroxysteroid dehydrogenase 2

Fitoterapia. 2017 Sep:121:112-117. doi: 10.1016/j.fitote.2017.07.004. Epub 2017 Jul 12.

Abstract

Taxifolin is a flavonoid in food plants. Kidney 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) is an NAD+-dependent oxidase that inactivates glucocorticoid cortisol (human) or corticosterone (rodents) into biologically inert 11 keto glucocorticoids. The present study investigated the effects of taxifolin on rat and human kidney microsomal 11β-HSD2. Taxifolin noncompetitively inhibited rat and human 11β-HSD2 against steroid substrates, with IC50 values of 33.08 and 13.14μM, respectively. Administration of 5 and 10mg/kg taxifolin for 30min ex vivo inhibited 11β-HSD2 significantly and also in vivo decreased cortisol metabolism, as shown in the significant increase of area under curve (AUC). This result shows that taxifolin is a potent 11β-HSD2 inhibitor, possibly causing side effects.

Keywords: 11β-Hydroxysteroid dehydrogenase 2; Enzyme inhibition; Glucocorticoid; Noncompetitive; Taxifolin.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors*
  • Animals
  • Corticosterone / metabolism
  • Glucocorticoids / metabolism
  • Humans
  • Male
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Glucocorticoids
  • Quercetin
  • taxifolin
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Corticosterone