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Ethanolic valeriana officinalis extracts and valerenic acid delay pentylenetetrazole-induced seizures in adult zebrafish (Danio rerio): interactions with GABAa, glutamate, and adenosine receptors


Pharmacy & Pharmacology International Journal
Bianca A Torres-Hernández,1 Kiara Serrano,2 Yolimar Santiago-Cruz,2 Zuleyma E ToledoNieves,2 Claudia Jordán,2 Marely SantiagoVázquez,2 José G Ortiz2

Abstract

Background: Anticonvulsant properties have been attributed to Valerian formulations and patients with epilepsy have reported using Valerian as complementary medicine. In zebrafish, Valerian ethanolic extracts (ValE) and valerenic acid (VA) have anticonvulsant properties.
Hypothesis/Purpose: We evaluated the possible role of GABAa, Adenosine, or Glutamate in the anticonvulsant properties of Valerenic acid (VA) and ethanolic Valerian extract (ValE) in zebrafish.
Study Design: Animals were pre-incubated with the selective antagonist and later with ethanolic Valerian extracts or valerenic acid. Untreated animals served as controls. The zebrafish were then exposed to pentylenetetrazole (3 mg/mL), and the latency to seizurelike behavior was recorded.
Results: GABAzine, a GABAa antagonist, reduces the anticonvulsant effects of ValE but not those of VA. On the other hand, A1 (DPCPX) and A2 (SCH-28261) antagonism altered the anticonvulsant effects of VA but not those of ValeE. The anticonvulsant effects of ValE are reduced by the antagonism of NMDA (D-AP5) and KA (UDP-301) but not by AMPA (NBQX). Metabotropic glutamate receptor (mGluR I/PHCCC, mGluR II/EGLU, mGluR III/CPPG) antagonists alter the effects of VA without altering ValE.
Conclusions: VA and ValE selectively interact with GABAa, Adenosine, and Glutamate receptors. Differences between the effects on the anticonvulsant effects of VA and ValE suggest that VA is not the only active constituent responsible for the ValE anticonvulsant activity. 

Keywords

valerian, seizures, zebrafish, GABA, adenosine, glutamate

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