Enhancement of heparin and heparin disaccharide absorption by thePhytolacca americana saponins

We studied the effects of phytolaccosides, saponins fromPhytolacca americana, on the intestinal absorption of heparinin vitro andin vivo. The absorption enhancing activity of these compounds (phytolaccosides B, D₂, E, F., G and I) was determined by changes in transepithelial electrical resistance (TEER) and the transport amount of heparin disaccharide, the major repeating unit of heparin, across Caco-2 cell monolayers. With the exception of phytolaccoside G, all of them decreased TEER values and increased the permeability in a dose-dependent and time-dependent manner.In vitro, phytolaccosides B, D₂, and E showed significant absorption enhancing activities, while effects by phytolaccoside F and I were mild.In vivo, phytolaccoside E increased the activated partial thromboplastin time (APTT) and thrombin time, indicating that phytolaccoside E modulated the transport of heparin in intestinal route. Our results suggest that a series of phytolaccosides fromPhytolacca americana can be applied as pharmaceutical excipients to improve the permeability of macromolecules and hydrophilic drugs having difficulty in absorption across the intestinal epithelium.