Endogenous digoxin-like activity of mammalian-lignans and their derivatives.
A comparative study was made on the endogenous digoxin-like activity of sixteen mammalian-type lignan derivatives including enterolactone and enterodiol. Cross-reactivity to antidigoxin antibody, inhibition of dog kidney Na+,K+-ATPase, and ouabain displacing activity against [3H]ouabain binding to human erythrocytes on the part of these derivatives were examined and compared in all cases with that of ouabain. meso-2,3-Dibenzylbutane-1,4-diol (meso-HA-1) was found to possess the most potent cross-reactivity to antidigoxin antibody. Several lignans, particularly HA-1 (either meso or dl), dl-2,3-bis(3-methoxybenzyl)butane-1,4-diol(HA-4), dl-2,3-bis(3,4-dimethoxybenzyl)butane-1,4-diol(HA-10), dl-2,3-bis(3,4-dimethoxybenzyl)-1,4-dimethoxybutane(HA-11), and trans-2,3-bis(3,4-dimethoxybenzyl)-gamma-butyrolactone(HA-14) were capable of inhibiting Na+,K+-ATPase activity with IC50 at a concentration less than 5 x 10(-4) M. Meso-HA-1, HA-11 and HA-14 also showed [3H]ouabain displacement activity with IC50 at a concentration of 10(-4)-10(-3) M. These determinations of activity were made at doses 100-1000 times those of ouabain. The synthetic lignans are considered to derive in vivo from plant material usually present in fibrous food. Based on the data obtained, some lignans may possibly be endogenous digitalis-like substances.
Hirano
T
T
Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Oka
K
K
Naitoh
T
T
Hosaka
K
K
Mitsuhashi
H
H
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism*; D002072:Butylene Glycols; D002298:Cardenolides; D003429:Cross Reactions; D004077:Digoxin / Q000378:metabolism; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D017705:Lignans; D010042:Ouabain / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011863:Radioimmunoassay; D012503:Saponins; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
C000591381:3-bis(3-methoxybenzyl)butane-1,4-diol; D001798:Blood Proteins; D002072:Butylene Glycols; D002298:Cardenolides; D017705:Lignans; D010936:Plant Extracts; D012503:Saponins; C034504:digoxin-like factors; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase