57.    Depressant effects of a series of Argentinian valerian species in mice

The most commonly prescribed drugs to treat insomnia are benzodiazepines (BDZ), which are also used to reduce anxiety. These molecules are ligands of the GABAA receptor, major inhibitory receptor in the central nervous system (CNS). Despite some BDZs are good sleep inducers, they produce unwanted side effects (amnesia, muscle relaxation, dependence). Folkloric or galenic preparations of the well-known valerian roots, such as Valeriana officinalis L. and V. wallichii DC., have been used as sedatives, anxiolytics and sleep inducers since ancient times. Since our country harbours several thousands of plant species, which lack scientific information, and many of them are used in folk medicine, our aim is to obtain purified and standardized extracts and/or active principles from medicinal plants from our country. We intend to provide the pharmaceutical industry with novel raw materials of suitable quality for the preparation of herbal medicines and/or medicinal  specialties with CNS effects to treat patients affected by anxiety, stress, depression, insomnia, pain and/or Alzheimer or Parkinson disease. Herein we performed a comparative study of the potential effects of a series of ethanolic extracts from the subterranean parts of Argentinian valerian species: V. carnosa Sm., V. clarionifolia Phil . and V. macrorhiza DC., from “Patagonia Argentina”; and V. ferax (Griseb.) Höck and V. effusa Griseb., from the central part of our country, and V. officinalis (as the reference plant) aiming to validate their traditional use in our country. Their possible sedative/anxiolytic and sleep inducing properties in vivo, in mice, have been tested. Moreover, the presence of ligands of the benzodiazepine binding site of the GABAA receptor (BDZ-bs) has been evaluated in vitro. The sedative and sleep inducing properties of the hydroalcoholic (70 %) extracts (underground parts,
10 % w/v), which were previously extracted with petroleum ether (to eliminate undesirable compounds: valepotriates and baldrinals), from these Argentinian plants were evaluated in the “holeboard”, “locomotor activity” and the “thiopental-induced loss of righting reflex” assays. All the tested extracts evidenced the presence of ligands for the BDZ-bs and also were able to induce sleep at the dose tested (500 mg/kg, i.p. in mice). But, only, V. carnosa and V. clarionifolia extracts (500 mg/kg, i.p. in mice) showed sedative and anxiolytic-like activities, respectively. Data show that Argentinian valerian species are active on the CNS through the GABAA
receptor, validating its folkloric use as anxiolytic/sedative and sleep enhancers. Moreover, additional efforts should be made to deeply study both, V. carnosa and V. clarionifolia. The results obtained from this study suggests the potential use of Argentinian valerian species as an alternative natural source for the treatment of CNS disorders to provide a better quality of life to patients affected by anxiety, stress, and insomnia.