Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi

J Pharm Pharmacol. 1990 Oct;42(10):723-6. doi: 10.1111/j.2042-7158.1990.tb06568.x.

Abstract

Two chalcone derivatives, xanthoangelol (1) and 4-hydroxyderricin (II) isolated from Angelica keiskei Koidzumi, inhibited pig gastric H+, K(+)-ATPase with IC50 values of 1.8 and 3.3 microM, respectively. The inhibition by I or II was competitive with respect to ATP and was non-competitive with respect to K+ I and II also inhibited K+, stimulated p-nitrophenyl phosphatase, with IC50 values of 1.3 and 3.5 microM, respectively. Proton transport in-vitro was inhibited by I or II, in a dose-dependent manner, 1 at 100 mg kg-1, i.p. significantly inhibited acid secretion and the formation of stress-induced gastric lesions. These results suggest that the antisecretory effect of 1 is due to the inhibition of gastric H+, K(+)-ATPase.

MeSH terms

  • 4-Nitrophenylphosphatase / antagonists & inhibitors
  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Animals
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology*
  • Gastric Acid / metabolism
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / enzymology
  • H(+)-K(+)-Exchanging ATPase
  • In Vitro Techniques
  • Male
  • Microsomes / enzymology*
  • Plants, Medicinal / analysis*
  • Potassium / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Spectrometry, Fluorescence
  • Swine

Substances

  • 4-hydroxyderricin
  • Chalcone
  • xanthoangelol
  • 4-Nitrophenylphosphatase
  • Adenosine Triphosphatases
  • H(+)-K(+)-Exchanging ATPase
  • Potassium