Betulin binds to gamma-aminobutyric acid receptors and exerts anticonvulsant action in mice |
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Authors: | Muceniece Ruta Saleniece Kristine Rumaks Juris Krigere Liga Dzirkale Zane Mezhapuke Rudolfs Zharkova Olga Klusa Vija |
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Institution: | aUniversity of Latvia, Faculty of Medicine, Sarlotes St. 1a, Riga, LV-1001, Latvia;bLatvian Institute of Organic Synthesis, Aizkraukles St. 21, Riga, LV-1006, Latvia |
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Abstract: | The lupane type pentacyclic triterpenes: lupeol, betulin, and betulinic acid are widely distributed natural compounds. Recently, pharmaceutical compositions from plant extracts (family Marcgraviaceae) containing betulinic acid, have been patented as anxiolytic remedies. To extend our knowledge of the CNS effects of the triterpenes, we suggest here that the chemically related lupeol, betulin and betulinic acid may interact with the brain neurotransmitter γ-aminobutyric acid (GABA) receptors in vitro and in vivo. Using radioligand receptor-binding assay, we showed that only betulin bound to the GABAA-receptor sites in mice brain in vitro and antagonised the GABAA-receptor antagonist bicuculline-induced seizures in mice after intracisternal and intraperitoneal administration. Neither betulinic acid nor lupeol bound to GABAA receptor nor did they inhibit bicuculline-induced seizures in vivo. These findings demonstrate for the first time the CNS effects of betulin in vivo, and they also show distinct GABAA-receptor-related properties of lupane type triterpenes.These findings may open new avenues in understanding the central effects of betulin, and they also indicate possibilities for novel drug design on the basis of betulin structure. |
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Keywords: | Betulin Betulinic acid Lupeol GABA Receptor binding Bicuculline seizures |
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