Neuroactive flavonoid glycosides from Tilia petiolaris DC. extracts.

LEONARDO M. LOSCALZO; CRISTINA WASOWSKI; MARIEL MARDER

Blue Mountains, NSW, Australia

Conferencia; Faculties of Health Research Conference “From Cell to Society 6”.; 2008

University of Sydney

Anxiety, depression and insomnia are very common mental disorders; the efficacy of present treatments is frequently diminished by side effects. Nature is a good source of pharmacologically active compounds. As a consequence plants have been extensively applied to counter all kinds of ailments, a procedure that is still in use today. We have demonstrated that some flavonoids possess affinity for the central benzodiazepine binding site of the GABAA receptor, and exert anxiolytic but not sedative effects in rodents. 1 We have identified in valerian extracts two flavonoid glycosides, hesperidin and linarin, with sedative and sleep-enhancing activities in mice.2,3 Tilia species are traditional medicinal plants widely used in Latin America as sedatives and tranquilizers. For this purpose, the infusion of their inflorescences is used to prepare a tea. In order to identify the active constituents in the hydroalcoholic extract of Tilia petiolaris DC, a bio-guided purification was performed. Isoquercitrin (ISO), quercetin 3-O-glucoside-7-O-rhamnoside (QUE) and kaempferol 3-O-glucoside-7-O-rhamnoside (KAE) were isolated, identified and their behavioural actions were measured in the holeboard, locomotor activity and thiopental induced sleeping time tests in mice (10 and 30 mg/kg, i.p.). ISO, QUE and KAE exhibited clear depressant actions. Considering the sedative and the thiopental-induce sleeping time effects obtained and the doses injected, the strength of their actions in decreasing order was: QUE>KAE>ISO. In addition, the effects of an infusion, containing these compounds among others, were assessed in mice. The results indicated that the infusion induced significant reductions in all the parameters measured suggesting a remarkable depressant action. These results demonstrate the occurrence of new active principles in Tilia, and taking into account that the isolated flavonoid glycosides are present in various species of this plant,4 they may explain its ethnopharmacological use as a tranquillizer. In addition synergistic and/or additive effects are likely to occur.   1  M. Marder, A. C. Paladini. Current Topics in Medicinal Chemistry, 2: 853-867 (2002). 2 M. Marder, H. Viola, C. Wasowski, S. Fernández, J. H. Medina, A. C. Paladini. Pharmacol. Biochem Behav., 75: 537-545 (2003). 3 S. Fernández, C. Wasowski, A. Paladini, M. Marder. Pharmacol. Biochem. Behav., 77: 399-404 (2004). 4 E. Aguirre-Hernández, A.L. Martínez, M.E. González-Trujano, J. Moreno, H. Vibrans and M. Soto-Hernández. J. Ethnopharmacol., 109: 140-145 (2007).