Inhibition of 11beta-hydroxysteroid dehydrogenase in guinea pig kidney by three bioflavonoids and their interactions with gossypol

Acta Pharmacol Sin. 2002 Jan;23(1):92-6.

Abstract

Aim: To study the effects of some bioflavonoids on the gossypol-induced hypokalemia.

Methods: The 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) protein was prepared from guinea pig kidney. The activity of 11beta-OHSD with NAD as the coenzyme was measured by HPLC. The drug interaction was analysed by isobolographic method.

Results: The 11beta-OHSD can be inhibited by some bioflavonoids. The IC50 (95 % confidence limits) values were: quercetin 164 (79 - 341) micromol/L, morin 913 (385 - 2173) micromol/L, and naringenin 2193 (1114 - 4315) micromol/L. When the 11beta-OHSD was treated with quercetin, tangeretin, morin, naringenin plus gossypol, the combination index (CI) values were 0.92, 0.85, 0.98, and 1.01 respectively.

Conclusion: The interaction of some bioflavonoids with gossypol might be one of the factors for gossypol-induced hypokalemia.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Animals
  • Depression, Chemical
  • Drug Synergism
  • Enzyme Inhibitors
  • Flavones*
  • Flavonoids / pharmacology*
  • Gossypol / adverse effects
  • Gossypol / pharmacology*
  • Guinea Pigs
  • Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • Hydroxysteroid Dehydrogenases / metabolism
  • Hypokalemia / chemically induced
  • Male
  • NAD / metabolism
  • Quercetin / pharmacology

Substances

  • Enzyme Inhibitors
  • Flavones
  • Flavonoids
  • NAD
  • morin
  • Quercetin
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • tangeretin
  • Gossypol