Inhibition of Na +, K +-ATPase by 1,2,3,4,6-Penta-O-galloyl-β-D-glucose, a major constituent of both moutan cortex and paeoniae radix

Abstract

The inhibition of Na∗,K +-ATPase activity by various constituents of Moutan Cortex and Paeoniae Radix was studied. 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (PGG), a major component of both crude drugs, strongly inhibited Na +,K +-ATPase activity (lC 50 = 2.5 x 10 -6 M), whereas galloylpaeoniflorin, benzoic acid, and catechin were weakly inhibitory, and albiflorin, oxypaeoniflorin, paeoniflorin, paeonol, and phenol were ineffective. The inhibition of Na +,K +-ATPase activity by PGG was decreased in the presence of BSA or phospholipids. The inhibition mode of PGG was noncompetitive with respect to ATP. The K 0.5 value for Na + was increased by the addition of PGG from 9.1 to 12.3 mM, whereas that for K + was not altered. PGG also inhibited K +-dependent p-nitrophenyl phosphatase activity with an IC 50 value of 5.3 x 10 -6 M, and the extent of the inhibition increased at higher concentrations of K +. The K 0.5 value for K + was decreased by the addition of PGG from 3.3 to 2.0 mM. These results suggested that the inhibition of Na +,K +-ATPase activity is caused by interaction of PGG with the enzyme in the E 2 state. The inhibitory effect of Moutan Cortex or Paeoniae Radix is considered to be mainly attributable to PGG.