Pharmacological research on natural substances in Latvia: Focus on lunasin, betulin, polyprenol and phlorizin.

In this concise review the current research in plant bioactive compound studies in Latvia is described. The paper summarizes recent studies on substances from edible plants (e.g., cereals and apples) or their synthetic analogues, such as peptide lunasin, as well as substances isolated from inedible plants (e.g., birch and conifer), such as pentacyclic triterpenes (e.g., betulin, betulinic acid, and lupeol) and polyprenols. Latvian researchers have been first to demonstrate the presence of lunasin in triticale and oats. Additionally, the impact of genotype on the levels of lunasin in cereals was shown. Pharmacological studies have revealed effects of lunasin and synthetic triterpenes on the central nervous system in rodents. We were first to show that synthetic lunasin causes a marked neuroleptic/cataleptic effect and that betulin antagonizes bicuculline-induced seizures (a GABA A receptor antagonist). Studies on the mechanisms of action showed that lunasin binds to dopamine D1 receptors and betulin binds to melanocortin and gamma-aminobutyric acid A receptors therefore we suggest that these receptors play an essential role in lunasin's and betulin's central effects. Recent studies on conifer polyprenols demonstrated the ability of polyprenols to prevent statin-induced muscle weakness in a rat model. Another study on plant compounds has demonstrated the anti-hyperglycemic activity of phlorizin-containing unripe apple pomace in healthy volunteers. In summary, research into plant-derived compounds in Latvia has been focused on fractionating, isolating and characterizing of lunasin, triterpenes, polyprenols and phlorizin using in vitro, and in vivo assays, and human observational studies.