Pentagalloylglucose, an antisecretory component of Paeoniae radix, inhibits gastric H+, K(+)-ATPase.
We purified a compound with strong inhibitory effect on H+, K(+)-ATPase from Paeoniae radix, which has been used in Japan for the treatment of gastritis and peptic ulcers. The compound was identified as 1,2,3,4,6,-penta-o-galloyl-beta-D-glucose by proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and fast atomic bombardment mass spectrometry. The IC50 of the compound for H+, K(+)-ATPase was 166 nmol/l. Kinetic analyses indicated that the inhibition of the enzyme by pentagalloylglucose was noncompetitive with respect to K+. Pentagalloylglucose had relatively weak inhibitory effects for Mg(+)-ATPase (IC50: > 10 mumol/l) and Na+, K(+)-ATPase (IC50: 2.7 mumol/l). Pentagalloylglucose also inhibited the accumulation of [14C]aminopyrine in parietal cells that had been isolated from guinea pig stomach and stimulated by 10 mumol/l histamine (IC50: 7.8 mumol/l) and 1 mmol/l dbc-AMP (IC50: 10 mumol/l). These results suggest that pentagalloylglucose is a potent inhibitor of H+, K(+)-ATPase and may be responsible for inhibition of acid secretion by Paeoniae radix.
Ono
K
K
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Sawada
T
T
Murata
Y
Y
Saito
E
E
Iwasaki
A
A
Arakawa
Y
Y
Kurokawa
K
K
Hashimoto
Y
Y
D000632:Aminopyrine / Q000037:antagonists & inhibitors; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D006168:Guinea Pigs; D047348:Hydrolyzable Tannins; D007564:Japan; D007700:Kinetics; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D054328:Proton Pump Inhibitors; D013634:Tannins / Q000302:isolation & purification / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D054328:Proton Pump Inhibitors; D013634:Tannins; D000632:Aminopyrine; C435084:pentagalloylglucose; D017301:Ca(2+) Mg(2+)-ATPase