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Journal of Ethnopharmacology 2012 May 2
Rhus parviflora and its biflavonoid constituent, rhusflavone, induce sleep through the positive allosteric modulation of GABA(A)-benzodiazepine receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhus parviflora is referred as 'Tintidikah' in traditional medicinal system of south Asia (Ayurveda). It is used in treatment of Vata vikara, a condition related to neurological complications as well as cure for stomach disorders. MATERIALS AND METHODS: Dried and powdered fruits of R. parviflora were extracted with 80% aqueous methanol (RPME). The concentrated extract was successively partitioned with distilled water, ethyl acetate, and n-butanol. All extracts, as well as isolated biflavonoids from R. parviflora, were evaluated for their affinity to the benzodiazepine binding site of GABA(A) receptor. The sedative-hypnotic effects of the fractions were evaluated by measuring sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of the extract fractions. RESULTS: Oral administration of RPME (125mg/kg, 250mg/kg, 500mg/kg, and 1000mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in mice treated with pentobarbital. The methanol extract produced a hypnotic effect that was fully blocked by (3)H-Ro 15-1788 flumazenil (FLU). Further, among the solvent fractions, the ethyl acetate fraction exhibited significant activity. Among the isolated compounds, biflavonoids mesuaferrone B (1), rhusflavone (3), and agathisflavone (4) competitively inhibited FLU binding with a K(i) of 0.280µM, 0.045µM, and 0.091µM, respectively. In addition, analysis of the sedative-hypnotic effects of rhusflavone, as well as those of the ethyl acetate, n-butanol, and distilled water fractions revealed that the modulation of both the ethyl acetate fraction and biflavonoid rhusflavone (3) are the most potent in inducing sleep. CONCLUSION: The presence of conjugated ketone and C6-C8? biflavonoid linkage in rhusflavone may be responsible for BZD-site of the GABA(A) leading to decrease in sleep latency and increase sleep duration. Copyright © 2012. Published by Elsevier Ireland Ltd.

DHARA ID: D053353 Pubmed ID: 22579675

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