Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.
BACKGROUND
Kyllinga brevifolia rhizomes (Cyperaceae) are used in Paraguayan traditional medicine as a refreshing beverage, and is claimed to own digestive, diuretic, sedative, tonic, antispasmodic and sudorific properties. We have previously reported that its hydro- ethanolic rhizome extract possess sedative, anxiolytic and anti-aggressive-like effects in mice. However, information on its potential for treatment of syndromes associated with mood disorders is scarce.


OBJECTIVE
The purpose of this study is to characterize the putative antidepressant-like effects of the hydro-ethanolic extract (CEKb) and the ethyl acetate fraction (KbF-ethyl-ac) obtained from the rhizome of K. brevifolia (Rottb) on male mice exposed to forced swimming test. Also, chemical characterization of the components of the active ethyl acetate fraction was described.


METHODS
The antidepressant-like effects of CEKb and KbF-ethyl-ac were measured using the forced swimming test (FST) performance of male mice in single (acute), short-term and chronic modalities. Treatments in all modalities were made 1h before swimming test. The KbF-ethyl-ac was analyzed by LC-DAD-ESI-MS and LC-ESI-MS/MS in order to identify the active components.


RESULTS
A single doses (1.0, 10.0 and 100.0mg/kg, p.o; p<0.05) of CEKb, in male mice provoked a significant reduction of the immobility time. Such effect was also observed with oral short-term treatment (7 days) with doses of 10.0 and 100.0mg/kg/day (p<0.05) of CEKb. Moreover, in the treatments during 14 days with doses of 1.0 (p<0.05), 10.0 (p<0.05), and 100.0 (p<0.001) mg/kg, p.o, of CEKb, a statistically significant reduction of the immobility time were induced. Additionally, in a different set of experiments acute dose of 1.0 (p<0.05) and 10.0 (p<0.01) mg/kg, p.o, of KbF-ethyl-ac in male mice, a significant reduction of the immobility time were provoked. Likewise, short-term treatment (7 days) with 1.0, and 10.0mg/kg (p<0.05); and after 14 days of treatment with 0.01 (p<0.01) 0.1 (p<0.001), 1.0 (p<0.001), and 10.0 (p<0.05) mg/kg of KbF-ethyl-ac in male mice, a statistically significant reduction of the immobility time, were observed. Imipramine 32mg/kg/days, i.p, induced a statistically significant reduction of immobility time and was used as positive control to validate the method employed. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEKb or KbF-ethyl-ac (acute, short-term or chronic). Both, efficacy and potency were higher when repeated administration of CEKb was used, and surprisingly the efficacy of 1.0mg/kg of KbF-ethyl-ac (14 days) was similar to imipramine. The main constituents of the KbF-ethyl-ac were identified as catechins and their dimers by LC-DAD-ESI-MS and LC-ESI-MS/MS, according to their UV and MS spectra, as compared with the literature data. These results indicate an important antidepressant-like profile of action for the CEKb and KbF-ethyl-ac; and meanwhile, this effect may partially reside on catechins and their dimers isolated from the KbF-ethyl-ac.


CONCLUSIONS
These findings indicate that K. brevifolia exerts antidepressant -like effects in mice and suggest its potential usefulness for the treatment of depression in humans and encourage us to pursue the isolation of the molecules associated to the effect observed in CEKb and KbF-ethyl-ac, and to determine the mechanism of antidepressant-like effect of Kyllinga brevifolia using adequate complementary test.
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay. Electronic address: chellion@qui.una.py.
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Hellión-Ibarrola
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay.
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Montalbetti
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay.
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Heinichen
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay.
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Kennedy
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay.
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Campuzano
Departamento de Fitoquímica, Facultad de Ciencias Químicas. Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay.
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Alvarenga
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Asunción, Campus UNA, 1055, San Lorenzo, Paraguay.
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Ibarrola
D000085:Acetates / Q000737:chemistry*; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D027343:Rhizome / Q000737:chemistry*; D013550:Swimming / Q000502:physiology
D000085:Acetates; D000928:Antidepressive Agents; D010936:Plant Extracts; C007650:ethyl acetate
Antidepressant; Forced swimming test; Kyllinga brevifolia