Scopadulcic Acid B, a New Tetracyclic Diterpenoid from Scoparia dulcis L. Its Structure, H⁺, K⁺-Adenosine Triphosphatase Inhibitory Activity and Pharmacokinetic Behaviour in Rats

Abstract

The structure of scopadulcic acid B (2, SDB), a major ingredient of the Paraguayan herb "Typycha kuratu" (Scoparia dulcis L.), was elucidated mainly by comparison of its spectral data with that of scopadulcic acid A (1). SDB inhibited both the K⁺-dependent adenosine triphosphatase (ATPase) activity of a hog gastric proton pump (H⁺, K⁺-ATPase) with a value of 20-30μM for IC₅₀ and proton transport into grastric vesicles. Pharmacokinetic studies of SDB in rats indicated that plasma SDB concentrations after i.v. injection of the sodium salt of SDB (SDB-Na) were described reasonably well by a two-compartment open model with Michaelis-Menten elimination kinetics. Plasma concentrations after oral administration of SDB-Na or SDB showed a much slower decline than what was expected following the i. v. study. It was suggested that the sustained plasma level of SDB after oral administration of SDB-Na or SDB was accounted for by relatively slow but efficient gastro-intestinal absorption in rats.