Safety, pharmacokinetics and mechanism of lipid-lowering action of polysaccharide l-rhamnopyranosyl-6-o-methyl-galacturonan isolated from the birch leaves (betula pendula roth.)

Introduction. Biologically active substances of plant origin are the subject of study in the context of search and development of new pharmacological agents capable of influencing cholesterol metabolism in the body. The article presents the results of safety assessment, pharmacokinetics and mechanism of pharmacological activity of a new promising hypocholesterolemic agent –  L-rhamnopyranosyl-6-O-methyl-galacturonan, a polysaccharide isolated from the leaves of birch (Betula pendula Roth.).

Objective of the study – comprehensive study of pharmacokinetic parameters, safety and mechanisms of activity of  L-rhamnopyranosyl-6-O-methyl-galacturonan in vivo and in vitro.

Material and Methods. Evaluation of acute toxicity by single intragastric or intraperitoneal administration was performed on BALB/c mice and SD rats (Sprague-Dawley). To determine the effect of polysaccharide on bile acid excretion in rats with experimental hyperlipidaemia, faeces were collected for bile acid determination. Blood plasma was used in the evaluation of pharmacokinetics. Detection was performed using high-performance liquid chromatography mass spectrometry method. To assess the sorption activity of polysaccharide, polysaccharide or a comparison drug cholestyramine was added to a solution of cholic or deoxycholic acid, unbound bile acids were quantified. Light microscopy was used to visualise polysaccharide-bile acid complexes.

Results. After intragastric administration of polysaccharide at a dose of 1500 mg/kg the object of the study is practically not subjected to absorption from the digestive tract and can exert its hypolipidemic effect through effects directly in the intestinal lumen. Polysaccharide does not penetrate into organs and tissues and has no systemic action, it is completely excreted through the GI tract. According to the results of acute toxicity experiments the investigated substance can be characterised as practically non-toxic. The mechanism of hypolipidemic action of polysaccharide is associated with its ability to bind bile acids in the intestine, which is confirmed by the obtained data on the increase in the excretion of bile acids with faeces in laboratory animals receiving polysaccharide, and the established ability of polysaccharide to bind bile acids in vitro.

Conclusions. After oral administration, L-rhamnopyranosyl-6-O-methyl-galacturonan is practically not absorbed from the digestive tract, has no toxic effects, and exerts its hypolipidemic effect by binding bile acids in the intestinal lumen.