Inhibition of gastric H+, K(+)-ATPase by chalcone derivatives, xanthoangelol and 4-hydroxyderricin, from Angelica keiskei Koidzumi.
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.
Murakami
S
S
Research Center, Taisho Pharmaceutical Co. Ltd, Saitama, Japan.
Kijima
H
H
Isobe
Y
Y
Muramatsu
M
M
Aihara
H
H
Otomo
S
S
Baba
K
K
Kozawa
M
M
D009597:4-Nitrophenylphosphatase / Q000037:antagonists & inhibitors; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D010946:Plants, Medicinal / Q000032:analysis*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence; D013552:Swine
C068243:4-hydroxyderricin; D002599:Chalcone; C068244:xanthoangelol; D009597:4-Nitrophenylphosphatase; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium