The effects of escins Ib and IIb isolated from horse chestnuts on Mg2+ absorption from the digestive tract and the role of endogenous nitric oxide (NO) were investigated in mice. Test samples were given orally to fasted mice 30, 120, 180, 240 and 300 min before administration of 0.5 M MgSO4 (10 ml/kg, p.o.). The serum Mg2+ levels were determined 30, 60, 120 and 180 min after administration of MgSO4. Escins Ib and IIb (12.5 and 25 mg/kg) significantly increased the serum Mg2+ by 10.0-27.3%, 30, 120 and 180 min after administration of the samples, and 30, 60, 120 and 180 min after administration of MgSO4. Escins Ib and IIb (12.5 mg/kg) significantly decreased the Mg2+ content in the small intestinal fluid in MgSO4-loaded mice, but did not increase the serum Mg2+ levels in normal mice. The effects of escins Ib and IIb (12.5 mg/kg) on serum Mg2+ levels were attenuated in a dose-related manner by the pretreatment with N-G-nitro-L-arginine methyl ester (L-NAME, 3-20 mg/kg, i.p., an inhibitor of constitutive and inducible NO synthase), but not with D-NAME (10 mg/kg, i.p., the inactive enantiomer of L-NAME) or dexamethasone (0.05 and 0.5 mg/kg, s.c., an inhibitor of inducible NO synthase). The effect of L-NAME was reversed by L-arginine (600 mg/kg, i.p., a substrate of NO synthase), but not by D-arginine (900 mg/kg, i.p., the enantiomer of L-arginine). These results suggest that escins Ib and IIb enhance Mg2+ absorption from the digestive tract in mice, in which the constitutive, but not the inducible, NO synthase plays an important role. (C) 2000 Elsevier Science B.V. All rights reserved.