Abstract

Latua pubiflora (Griseb) Phil. Is a native shrub of the Solanaceae family that grows freely in southern Chile and is employed among Mapuche aboriginals to induce sedative effects and hallucinations in religious or medicine rituals since prehispanic times. In this work, the pentobarbital-induced sleeping test and the elevated plus maze test were employed to test the behavioral effects of extracts of this plant in mice. The psychopharmacological evaluation of L. pubiflora extracts in mice determined that both alkaloid-enriched as well as the non-alkaloid extracts produced an increase of sleeping time and alteration of motor activity in mice at 150 mg/Kg. The alkaloid extract exhibited anxiolytic effects in the elevated plus maze test, which was counteracted by flumazenil. In addition, the alkaloid extract from L. pubiflora decreased [3H]-flunitrazepam binding on rat cortical membranes. In this study we have identified 18 tropane alkaloids (peaks 1–4, 8–13, 15–18, 21, 23, 24, and 28), 8 phenolic acids and related compounds (peaks 5–7, 14, 19, 20, 22, and 29) and 7 flavonoids (peaks 25–27 and 30–33) in extracts of L. pubiflora by UHPLC-PDA-MS which are responsible for the biological activity. This study assessed for the first time the sedative-anxiolytic effects of L. pubiflora in rats besides the high resolution metabolomics analysis including the finding of pharmacologically important tropane alkaloids and glycosylated flavonoids.

Highlights

  • Natural product’s research is very important since they represent a rich source of bioactive compounds as new molecules for drug discovery and development (Atanasov et al, 2015; Waltenberger et al, 2016)

  • The major tropane alkaloids -scopolamine and atropine- were present in 5.7 and 21%, respectively, in the Alkaloids-Enriched Extract (ALK) extract used for pharmacological experiments

  • In our metabolomics analysis we have identified 19 tropane alkaloids, 8 phenolic acids and related compounds and 7 flavonoids in extracts of L. pubiflora by Ultra-high performance liquid chromatography (UHPLC)-Photodiode array detector (PDA)-MS, which are the responsible agents for the bioactivity

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Summary

Introduction

Natural product’s research is very important since they represent a rich source of bioactive compounds as new molecules for drug discovery and development (Atanasov et al, 2015; Waltenberger et al, 2016). (Solanaceae family, Figure 1), grows freely in Southern Chile along Cordillera de la Costa from Valdivia to Llanquihue regions (from 38◦S to 43◦S at 500–900 m height above sealevel) This unique species is the only member of the genus and has an important mystic role in the Mapuche indigenous culture for its putative spiritual, sedative and medicinal benefits (Olivares, 1995). Anthropological research in Chile has shown that Solanaceae species were smoked in ancient rituals (Echeverria and Niemeyer, 2013; Echeverria et al, 2014; Carrasco et al, 2015) and within them L. pubiflora (Planella et al, 2016) This species has been consumed in different preparations (e.g., infusions, cigarettes) which can cause sedation, mouth dryness, fever, pupillary dilation, delirium, and convulsions (Olivares, 1995) depending on the doses used. Since the herbal tea of this plant contained several alkaloids and flavonoids (Echeverria and Niemeyer, 2012), in this study two different

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